Diffeological, Fr\"{o}licher, and Differential Spaces

Differential calculus on Euclidean spaces has many generalisations. In particular, on a set $X$, a diffeological structure is given by maps from open subsets of Euclidean spaces to $X$, a differential structure is given by maps from $X$ to $\mathbb{R}$, and a Fr\"{o}licher structure is given by maps from $\mathbb{R}$ to $X$ as well as maps from $X$ to $\mathbb{R}$. We illustrate the relations between these structures through examples.Comment: 21 page

The effect of visual search strategy and overlays on visual inspection of castings

In the domain of inspecting particularly the casting industry there is currently a great deal of subjectivity in the visual inspection of castings. This subjectivity results in high rates of miss and false alarm outcomes among workers inspecting castings. These events lead to costly rework and end user rejection of product. Due to this, there is much interest in improving the inspection methods to detect anomalies. This research involves using various methods including search pattern training, as well as visual overlays, to augment the way inspectors inspect the casting. This is then compared to a control group. The results show the experimental groups that received search pattern training were superior to the standard training/control group. However, the group that utilizes an overlay was not superior to the control group despite the similar raster training, indicating the overlay methods used is distracting to the user

Drug Delivery: Enabling Technology for Drug Discovery and Development. iPRECIO® Micro Infusion Pump: Programmable, Refillable, and Implantable

Successful drug delivery using implantable pumps may be found in over 12,500 published articles. Their versatility in delivering continuous infusion, intermittent or complex infusion protocols acutely or chronically has made them ubiquitous in drug discovery and basic research. The recent availability of iPRECIO®, a programmable, refillable, and implantable infusion pump has made it possible to carry out quantitative pharmacology (PKPD) in single animals. When combined with specialized catheters, specific administration sites have been selected. When combined with radiotelemetry, the physiologic gold standard, more sensitive and powerful means of detecting drug induced therapeutic, and/or adverse effects has been possible. Numerous application examples are cited from iPRECIO® use in Japan, United States, and Europe with iPRECIO® as an enabling drug delivery device where the refillable and programmability functionality were key benefits. The ability to start/stop drug delivery and to have control periods prior dosing made it possible to have equivalent effects at a much lower dose than previously studied. Five different iPRECIO® applications are described in detail with references to the original work where the implantable, refillable, and programmable benefits are demonstrated with their different end-points

Analysis of Nonlinear Synchronization Dynamics of Oscillator Networks by Laplacian Spectral Methods

We analyze the synchronization dynamics of phase oscillators far from the synchronization manifold, including the onset of synchronization on scale-free networks with low and high clustering coefficients. We use normal coordinates and corresponding time-averaged velocities derived from the Laplacian matrix, which reflects the network's topology. In terms of these coordinates, synchronization manifests itself as a contraction of the dynamics onto progressively lower-dimensional submanifolds of phase space spanned by Laplacian eigenvectors with lower eigenvalues. Differences between high and low clustering networks can be correlated with features of the Laplacian spectrum. For example, the inhibition of full synchoronization at high clustering is associated with a group of low-lying modes that fail to lock even at strong coupling, while the advanced partial synchronizationat low coupling noted elsewhere is associated with high-eigenvalue modes.Comment: Revised version: References added, introduction rewritten, additional minor changes for clarit

Clustering and Synchronization of Oscillator Networks

Using a recently described technique for manipulating the clustering coefficient of a network without changing its degree distribution, we examine the effect of clustering on the synchronization of phase oscillators on networks with Poisson and scale-free degree distributions. For both types of network, increased clustering hinders global synchronization as the network splits into dynamical clusters that oscillate at different frequencies. Surprisingly, in scale-free networks, clustering promotes the synchronization of the most connected nodes (hubs) even though it inhibits global synchronization. As a result, scale-free networks show an additional, advanced transition instead of a single synchronization threshold. This cluster-enhanced synchronization of hubs may be relevant to the brain with its scale-free and highly clustered structure.Comment: Submitted to Phys. Rev.

Genetic structure and diversity of a rare woodland bat, Myotis bechsteinii: comparison of continental Europe and Britain

The Bechstein’s bat (Myotis bechsteinii) is a rare sedentary bat considered to be highly reliant on the presence of ancient woodland. Understanding the genetic connectivity and population structure of such elusive mammals is important for assessing their conservation status. In this study, we report the genetic diversity and structure of M. bechsteinii across Britain and Europe. Assessments were made using 14 microsatellite markers and a 747 bp region of the mitochondrial cytochrome b gene. Nuclear DNA (microsatellites) showed high levels of genetic diversity and little inbreeding across the species range, though genetic diversity was slightly lower in Britain than in mainland Europe. Bayesian and spatial PCA analysis showed a clear separation between the British and European sites. Within Europe, the Italian population south of the Alps was isolated from the other sites. In Britain, there was genetic structuring between the northern and southern part of the geographical range. Despite there being little genetic divergence in mitochondrial DNA (mtDNA) sequences throughout most of Europe, the mtDNA patterns in Britain confirmed this separation of northern and southern populations. Such genetic structuring within Britain—in the absence of any obvious physical barriers—suggests that other factors such as land-use may limit gene-flow

Targeting Mitochondrial Dysfunction in CNS Injury Using Methylene Blue; Still a Magic Bullet?

Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose cellular homeostasis and can lead to eventual cell death. Targeting of mitochondrial dysfunction in various diseases has proven a successful approach, lending support to mitochondria as a pivotal player in TBI cell death and loss of behavioral function. Within this mixed mini review/research article there will be a general discussion of mitochondrial bioenergetics, followed by a brief discussion of traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. We will also give an overview of one relatively new TBI therapeutic approach, Methylene Blue, currently being studied to ameliorate mitochondrial dysfunction following brain injury. We will also present novel experimental findings, that for the first time, characterize the ex vivo effect of Methylene Blue on mitochondrial function in synaptic and non-synaptic populations of mitochondria

Transient Dynamics of Sparsely Connected Hopfield Neural Networks with Arbitrary Degree Distributions

Using probabilistic approach, the transient dynamics of sparsely connected Hopfield neural networks is studied for arbitrary degree distributions. A recursive scheme is developed to determine the time evolution of overlap parameters. As illustrative examples, the explicit calculations of dynamics for networks with binomial, power-law, and uniform degree distribution are performed. The results are good agreement with the extensive numerical simulations. It indicates that with the same average degree, there is a gradual improvement of network performance with increasing sharpness of its degree distribution, and the most efficient degree distribution for global storage of patterns is the delta function.Comment: 11 pages, 5 figures. Any comments are favore

Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled iNKT cell gene expression during ontogeny and in peripheral subsets as part of the Immunological Genome Project (ImmGen). High-resolution comparative transcriptional analyses defined developmental and subset-specific iNKT cell gene expression programs. In addition, iNKT cells were found to share an extensive transcriptional program with natural killer (NK) cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Strikingly, the NK- iNKT program also operated constitutively in γδT cells and in adaptive T cells following activation. Together, our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes