Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects.

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies

Agent swarms: cooperation and coordination under stringent communications constraint

Here we consider the communications tactics appropriate for a group of agents that need to ``swarm'' together in a highly adversarial environment. Specifically, whilst they need to exchange information with each other about their location and their plans; at the same time they also need to keep such communications to an absolute minimum. This might be due to a need for stealth, or otherwise be relevant to situations where communications are significantly restricted. Complicating this process is that we assume each agent has (a) no means of passively locating others, (b) it must rely on being updated by reception of appropriate messages; and if no such update messages arrive, (c) then their own beliefs about other agents will gradually become out of date and increasingly inaccurate. Here we use a geometry-free multi-agent model that is capable of allowing for message-based information transfer between agents with different intrinsic connectivities, as would be present in a spatial arrangement of agents. We present agent-centric performance metrics that require only minimal assumptions, and show how simulated outcome distributions, risks, and connectivities depend on the ratio of information gain to loss. We also show that checking for too-long round-trip-times can be an effective minimal-information filter for determining which agents to no longer target with messages.Comment: 11 pager, 7 figure

SURF IA Conflict Detection and Resolution Algorithm Evaluation

The Enhanced Traffic Situational Awareness on the Airport Surface with Indications and Alerts (SURF IA) algorithm was evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. SURF IA is designed to increase flight crew situation awareness of the runway environment and facilitate an appropriate and timely response to potential conflict situations. The purpose of the study was to evaluate the performance of the SURF IA algorithm under various runway scenarios, multiple levels of conflict detection and resolution (CD&R) system equipage, and various levels of horizontal position accuracy. This paper gives an overview of the SURF IA concept, simulation study, and results. Runway incursions are a serious aviation safety hazard. As such, the FAA is committed to reducing the severity, number, and rate of runway incursions by implementing a combination of guidance, education, outreach, training, technology, infrastructure, and risk identification and mitigation initiatives [1]. Progress has been made in reducing the number of serious incursions - from a high of 67 in Fiscal Year (FY) 2000 to 6 in FY2010. However, the rate of all incursions has risen steadily over recent years - from a rate of 12.3 incursions per million operations in FY2005 to a rate of 18.9 incursions per million operations in FY2010 [1, 2]. The National Transportation Safety Board (NTSB) also considers runway incursions to be a serious aviation safety hazard, listing runway incursion prevention as one of their most wanted transportation safety improvements [3]. The NTSB recommends that immediate warning of probable collisions/incursions be given directly to flight crews in the cockpit [4]

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized

The Spitzer Warm Mission Science Prospects

After exhaustion of its cryogen, the Spitzer Space telescope will still have a fully functioning two-channel mid-IR camera that will have sensitivities better than any other ground or space-based telescopes until the launch of JWST. This document provides a description of the expected capabilities of Spitzer during its warm mission phase, and provides brief descriptions of several possible very large science programs that could be conducted. This information is intended to serve as input to a wide ranging discussion of the warm mission science, leading up to the Warm Mission Workshop in June 2007

The Phase Space and Stellar Populations of Cluster Galaxies at z ~ 1: Simultaneous Constraints on the Location and Timescale of Satellite Quenching

We investigate the velocity vs. position phase space of z ~ 1 cluster galaxies using a set of 424 spectroscopic redshifts in 9 clusters drawn from the GCLASS survey. Dividing the galaxy population into three categories: quiescent, star-forming, and poststarburst, we find that these populations have distinct distributions in phase space. Most striking are the poststarburst galaxies, which are commonly found at small clustercentric radii with high clustercentric velocities, and appear to trace a coherent ``ring" in phase space. Using several zoom simulations of clusters we show that the coherent distribution of the poststarbursts can be reasonably well-reproduced using a simple quenching scenario. Specifically, the phase space is best reproduced if satellite quenching occurs on a rapid timescale (0.1 < tau_{Q} < 0.5 Gyr) after galaxies make their first passage of R ~ 0.5R_{200}, a process that takes a total time of ~ 1 Gyr after first infall. We compare this quenching timescale to the timescale implied by the stellar populations of the poststarburst galaxies and find that the poststarburst spectra are well-fit by a rapid quenching (tau_{Q} = 0.4^{+0.3}_{-0.4} Gyr) of a typical star-forming galaxy. The similarity between the quenching timescales derived from these independent indicators is a strong consistency check of the quenching model. Given that the model implies satellite quenching is rapid, and occurs well within R_{200}, this would suggest that ram-pressure stripping of either the hot or cold gas component of galaxies are the most plausible candidates for the physical mechanism. The high cold gas consumption rates at z ~ 1 make it difficult to determine if hot or cold gas stripping is dominant; however, measurements of the redshift evolution of the satellite quenching timescale and location may be capable of distinguishing between the two.Comment: 10 pages, 4 figures, submitted to the Ap

Biohybrid control of general linear systems using the adaptive filter model of cerebellum

© 2015 Wilson, Assaf, Pearson, Rossiter, Dean, Anderson and Porrill. The adaptive filter model of the cerebellar microcircuit has been successfully applied to biological motor control problems, such as the vestibulo-ocular reflex (VOR), and to sensory processing problems, such as the adaptive cancelation of reafferent noise. It has also been successfully applied to problems in robotics, such as adaptive camera stabilization and sensor noise cancelation. In previous applications to inverse control problems, the algorithm was applied to the velocity control of a plant dominated by viscous and elastic elements. Naive application of the adaptive filter model to the displacement (as opposed to velocity) control of this plant results in unstable learning and control. To be more generally useful in engineering problems, it is essential to remove this restriction to enable the stable control of plants of any order. We address this problem here by developing a biohybrid model reference adaptive control (MRAC) scheme, which stabilizes the control algorithm for strictly proper plants. We evaluate the performance of this novel cerebellar-inspired algorithm with MRAC scheme in the experimental control of a dielectric electroactive polymer, a class of artificial muscle. The results show that the augmented cerebellar algorithm is able to accurately control the displacement response of the artificial muscle. The proposed solution not only greatly extends the practical applicability of the cerebellar-inspired algorithm, but may also shed light on cerebellar involvement in a wider range of biological control tasks

A multizone cerebellar chip for bioinspired adaptive robot control and sensorimotor processing:A multizone cerebellar chip for bioinspired adaptive robot control and sensorimotor processing

The cerebellum is a neural structure essential for learning, which is connected via multiple zones to many different regions of the brain, and is thought to improve human performance in a large range of sensory, motor and even cognitive processing tasks. An intriguing possibility for the control of complex robotic systems would be to develop an artificial cerebellar chip with multiple zones that could be similarly connected to a variety of subsystems to optimize performance. The novel aim of this paper, therefore, is to propose and investigate a multizone cerebellar chip applied to a range of tasks in robot adaptive control and sensorimotor processing. The multizone cerebellar chip was evaluated using a custom robotic platform consisting of an array of tactile sensors driven by dielectric electroactive polymers mounted upon a standard industrial robot arm. The results demonstrate that the performance in each task was improved by the concurrent, stable learning in each cerebellar zone. This paper, therefore, provides the first empirical demonstration that a synthetic, multizone, cerebellar chip could be embodied within existing robotic systems to improve performance in a diverse range of tasks, much like the cerebellum in a biological system.</p