High-speed optical observations and simulation results of SonoVue microbubbles at low-pressure insonation

Abstract-Modified Rayleigh-Plesset models are commonly used to characterize the acoustic response of microbubbles under ultrasound exposure. In most instances these models have been parameterized through acoustic measurements taken from bulk suspensions of microbubbles. The aim of this study was to parameterize the Hoff model for the commercial contrast agent SonoVue using optically observed oscillations from individual microbubbles recorded with a high-speed camera. The shell elasticity model term was tuned to fit simulation data to the measured oscillations while the shell viscosity parameter was held constant at 1 Pa??s. The results demonstrate a limited ability of the model to predict the microbubble behavior. The shell elasticity parameter was found to vary proportionally between 10 and 80 MPa with the initial microbubble diameter, implying the viscoelastic shell terms are not a constant property of the shell material. Further analysis using a moving window optimization to probe the microbubble responses suggests that the elasticity of the shell can increase by up to 50% over the course of insonation, particularly for microbubbles oscillating nearer to their resonant frequency. Microbubble oscillations were modeled more successfully by incorporating a varying elasticity term into the model.     

Machine Learning Supporting Experimental Design for Product Development in the Lab

An interactive decision support framework is presented that assists lab researchers in finding optimal product recipes. Within this framework, an approach for sequential experimental design for black box models in a multicriteria optimization context is introduced. An additional criterion involving the prediction error to design new experiments is used with the goal to get a reliable estimate of the Pareto frontier within a few experimental iterations. The resulting decision support approach accompanies the chemist through the whole workflow and supports the user via interactive, graphical elements.     

Enabling Workflow-Oriented Science Gateways to Access Multi-Cloud Systems

In this paper we present a solution to cloud-enable workflow-oriented science gateways. The integration mechanism described in the paper is a generic method that can be followed by other gateway developers. The paper describes the principles and the concrete ways to integrate science gateways with multi-cloud systems. The concrete example to demonstrate the integration principles builds on the integration of WS-PGRADE/gUSE and the CloudBroker Platform (CBP). The integration of WS-PGRADE and the CloudBroker Platform offers a complete cloud-enabled science gateway platform for a diverse set of use-cases and user communities, with the availability to use mainstream cloud middleware types and services (Amazon, IBM, OpenStack, OpenNebula). The advantage of the integrated WS-PGRADE and CloubBroker Platform system is that if a domain-specific science gateway is customized from WS-PGRADE gateway framework it immediately inherits this cloud access flexibility, i.e. the user community of that gateway can access all the cloud types enabled by the integrated system presented.     

Once is too much: Conditioned changes in accumbens dopamine following a single saccharin-morphine pairing.

The present study tested whether presentation of a taste cue would support conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a single taste-drug pairing. Nondeprived male Sprague-Dawley rats were given 20-min access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter, experimental rats were injected with morphine (15 mg/kg ip); standard controls were injected with saline; and explicitly unpaired controls were injected with morphine, but approximately 24 hr later. All rats were then given one 20-min CS-only test. Microdialysis samples from the NAcc were measured over 20-min intervals before, during, and after CS access on the conditioning and test trial. The results showed that a single saccharin-morphine pairing led to a marked reduction in CS intake, and the reduction in intake was accompanied by a conditioned blunting of the accumbens dopamine response to the saccharin reward cue. In turn, a single exposure to the saccharin cue also blunted the unconditioned dopamine response to morphine. Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perceiving action-relevant properties of tools through dynamic touch: Effects of mass distribution, exploration style, and intention.

At issue in the present series of experiments was the ability to prospectively perceive the action-relevant properties of hand-held tools by means of dynamic touch. In Experiment 1, participants judged object move-ability. In Experiment 2, participants judged how difficult an object would be to hold if held horizontally, and in Experiments 3 and 4, participants rated how fast objects could be rotated. In each experiment, the first and second moments of mass distribution of the objects were systematically varied. Manipulations of wielding speed and orientation during restricted exploration revealed perception to be constrained by (a) the moments of mass distribution of the hand-tool system, (b) the qualities of exploratory wielding movements, and (c) the intention to perceive each specific property. The results are considered in the context of the ecological theory of dynamic touch. Implications for accounts of the informational basis of dynamic touch and for the development of a theory of haptically perceiving the affordance properties of tools are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins

The study objective was, firstly, to investigate whether anaesthesia with induced arterial hypotension would cause leakage of a biochemical marker of neuronal injury, adenylate kinase (AK), into the cerebrospinal fluid (CSF). (Definition: arterial hypotension = mean arterial pressure (MAP) 50-65 mmHg during > or = 10 min). Secondly, a subgroup of patients was examined with a limited battery of psychometric tests. Patients, scheduled for orthognathic surgery, were allocated to either hypotension (n = 20) or normotension (n = 20). Seventeen patients were subjected to psychometry. Arterial blood pressure was recorded continuously and controlled by adjustments of the administered concentration of the inhalational anaesthetic isoflurane. Fentanyl, an opioid, was given equally in both groups. A lumbar puncture was performed approximately 20 h post-operatively for a CSF sample, later analysed for AK activity. Neuropsychological tests were performed the day before surgery and the fourteenth day postoperatively. The CSF-AK value was pathologically increased ( > 0.040 U/L) in 24 patients (65%), of whom 9 were normotensive. There was no significant difference between the CSF-AK values in the hypotensive and normotensive groups, mean values were 0.082 (s.d. 0.051) and 0.066 (s.d. 0.059) U/L, respectively. The overall correlation between the 10 min MAP levels and the CSF-AK values was close to zero. In the pilot neuropsychological investigation some abnormalities were observed, indicating clinically significant adverse effects in four hypotensive patients, of whom two displayed pathologically increased CSF-AK values. At the group level, the correlation between the changes in psychometry and the measured CSF-AK values was poor. Increases in CSF-AK activities may be a non-specific occurrence in the perioperative interval, possibly indicating an adverse effect on the brain. Arterial hypotension could not be proven to explain the CSF-AK outcome.     

Inhibition of Caenorhabditis elegans vulval induction by gap-1 and by let-23 receptor tyrosine kinase

During induction of the Caenorhabditis elegans hermaphrodite vulva, a signal from the anchor cell activates the LET-23 epidermal growth factor receptor (EGFR)/LET-60 Ras/MPK-1 MAP kinase signaling pathway in the vulval precursor cells. We have characterized two mechanisms that limit the extent of vulval induction. First, we found that gap-1 may directly inhibit the LET-60 Ras signaling pathway. We identified the gap-1 gene in a genetic screen for inhibitors of vulval induction. gap-1 is predicted to encode a protein similar to GTPase-activating proteins that likely functions to inhibit the signaling activity of LET-60 Ras. A loss-of-function mutation in gap-1 suppresses the vulvaless phenotype of mutations in the let-60 ras signaling pathway, but a gap-1 single mutant does not exhibit excess vulval induction. Second, we found that let-23 EGFR prevents vulval induction in a cell-nonautonomous manner, in addition to its cell-autonomous role in activating the let-60 ras/mpk-1 signaling pathway. Using genetic mosaic analysis, we show that let-23 activity in the vulval precursor cell closest to the anchor cell (P6.p) prevents induction of vulval precursor cells further away from the anchor cell (P3.p, P4.p, and P8.p). This result suggests that LET-23 in proximal vulval precursor cells might bind and sequester the inductive signal LIN-3 EGF, thereby preventing diffusion of the inductive signal to distal vulval precursor cells.