Gesture, sound and place.

This paper discusses two multichannel interactive audiovisual artworks, Action A/V and SoundLabyrinth, that explore approaches to the experience of gesture, sound and place. Both works were situated in a geodesic dome frame and built within the Max, Ableton and Max for Live computer programs, and produced ostensibly similar outcomes, however the approaches taken by the two authors differ in intention, processes, and philosophy. These approaches were presented and discussed in workshops delivered at ISEA2013, on Sunday June 9 and Monday June 10 2013. In these workshops participants mprovised with the two systems, both through moving in the dome and by operating the related software, and discussed approaches and understandings of the three terms listed in the title of this paper

Resistance of Renal Cell Carcinoma to Sorafenib Is Mediated by Potentially Reversible Gene Expression

Purpose: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. Experimental Design: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. Results: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. Conclusions: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment

Morphological and Pathological Evolution of the Brain Microcirculation in Aging and Alzheimer’s Disease

Key pathological hallmarks of Alzheimer’s disease (AD), including amyloid plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2) nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND) group (average age 71 years) with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular “dysfunction” compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD

Timeout from concurrent schedules.

Response-contingent timeouts of equal duration and frequency were added to both alternatives of unequal concurrent schedules of reinforcement. For each of 4 pigeons in Experiment 1, relative response rates generally became less extreme as the frequency of timeout increased. In Experiment 2, relative response rates consistently approached indifference as the duration of timeout was increased. Variation in time allocation was less consistent in both experiments. Absolute response rates did not vary with the timeout contingency in either experiment. In a third experiment, neither measure of choice varied systematically when the duration of a postreinforcement blackout was varied. In contrast to the present results, preference has been shown to vary directly with the parameters of shock delivery in related procedures. The pattern of results in the first two experiments follows that obtained with other manipulations of the overall rate of reinforcement in concurrent schedules. The results of the third experiment suggest that an intertrial interval following reinforcement is not a critical feature of the overall rate of reinforcement