VLSI top-down design based on the separation of hierarchies

Despite the presence of structure, interactions between the three views on VLSI design still lead to lengthy iterations. By separating the hierarchies for the respective views, the interactions are reduced. This separated hierarchy allows top-down design with functional abstractions as exemplified by an experimental self-timed CMOS RISC computer design

Multiple time scales and multiform dynamics in learning to juggle.

To study the acquisition of perceptual-motor skills as an instance of dynamic pattern formation, we examined the evolution of postural sway and eye and head movements in relation to changes in performance, while 13 novices practiced 3-ball cascade juggling for 9 weeks. Ball trajectories, postural sway, and eye and head movements were recorded repeatedly. Performance improved exponentially, both in terms of the number of consecutive throws and the degree of frequency and phase locking between the ball trajectories. These aspects of performance evolved at different time scales, indicating the presence of a temporal hierarchy in learning. Postural sway, and eye and head movements were often 3:2 and sometimes 3:1 frequency locked to the ball trajectories. As a rule, the amplitudes of these oscillatory processes decreased exponentially at rates similar to that of the increase in the degree of phase locking between the balls. In contrast, the coordination between these oscillatory processes evolved exponentially at different time scales, apart from some erratic evolutions. Collectively, these findings indicate that skill acquisition in the perceptual-motor domain involves multiple time scales and multiform dynamics, both in terms of the development of the goal behavior itself and the evolution of the processes subserving this goal behavior

MicroRNA-122-dependent and -independent replication of Hepatitis C Virus in Hep3B human hepatoma cells

AbstractThe study of Hepatitis C Virus (HCV) has benefitted from the use of the Huh7 cell culture system, but until recently there were no other widely used alternatives to this cell line. Here we render another human hepatoma cell line, Hep3B, permissive to the complete virus life cycle by supplementation with the liver-specific microRNA miR-122, known to aid HCV RNA accumulation. When supplemented, Hep3B cells produce J6/JFH-1 virus titres indistinguishable from those produced by Huh7.5 cells. Interestingly, we were able to detect and characterize miR-122-independent replication of di-cistronic replicons in Hep3B cells. Further, we show that Argonaute-2 (Ago2) is required for miR-122-dependent replication, but dispensable for miR-122-independent replication, confirming Ago2's role in mediating the activity of miR-122. Thus Hep3B cells are a model system for the study of HCV, and miR-122 independent replication is a model to identify proteins involved in the function of miR-122

Abnormal reward valuation and event-related connectivity in unmedicated major depressive disorder

BACKGROUND: Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression. METHODS: Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression. RESULTS: Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression. CONCLUSIONS: Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment

Misophriopsis okinawensis sp. nov. (Crustacea: Copepoda) from Hyperbenthic Waters off Okinawa, South Japan, with Definitions of Related Genera Misophria Boeck, 1864 and Stygomisophria gen. nov.

A new misophrioid copepod Misophriopsis okinawensis (Crustacea) is reported from Kume Island, Okinawa, South Japan. A full description of the new misophrioid is presented, together with supplementary notes on the males of Misophria pallida Boeck, 1864. Consideration of the phylogeny of the new species led to a reassessment of the affinities between all the named species of Misophria Boeck, 1864 and Misophriopsis Boxshall, 1983. A new genus, Stygomisophira, is recognised based on Misophria kororiensis Boxshall et Iliffe, 1987. Diagnoses are presented of all three genera

No Increased Suggestibility to Placebo in Functional Neurological Disorder

BACKGROUND AND PURPOSE: On the basis of occasional strong placebo responses, increased susceptibility to placebo has been proposed as a characteristic of functional neurological disorder (FND). The aim of this study was to clarify whether people with FND have a stronger placebo analgesic response than healthy controls. METHODS: A study using a classic placebo paradigm, with additional conditioning and open-label components, was performed in 30 patients with FND, and in 30 healthy controls. Ratings of mildly to moderately painful electrotactile stimuli were compared before and after the application of a placebo “anaesthetic” cream versus a control cream, after an additional conditioning exposure, and after full disclosure (open-label component). RESULTS: Pain intensity ratings at the placebo compared to the control site were similarly reduced in both groups. The conditioning exposure had no additional effect. After placebo disclosure a residual analgesic effect remained. CONCLUSION: Patients with FND did not have stronger placebo responses than healthy controls. The notion of generally increased suggestibility or increased suggestibility to placebo in FND seems mistaken. Instead, occasional dramatic placebo responses may occur because functional symptoms are inherently more changeable than those due to organic disease

No Increased Suggestibility to Placebo in Functional Neurological Disorder

BACKGROUND AND PURPOSE: On the basis of occasional strong placebo responses, increased susceptibility to placebo has been proposed as a characteristic of functional neurological disorder (FND). The aim of this study was to clarify whether people with FND have a stronger placebo analgesic response than healthy controls. METHODS: A study using a classic placebo paradigm, with additional conditioning and open-label components, was performed in 30 patients with FND, and in 30 healthy controls. Ratings of mildly to moderately painful electrotactile stimuli were compared before and after the application of a placebo “anaesthetic” cream versus a control cream, after an additional conditioning exposure, and after full disclosure (open-label component). RESULTS: Pain intensity ratings at the placebo compared to the control site were similarly reduced in both groups. The conditioning exposure had no additional effect. After placebo disclosure a residual analgesic effect remained. CONCLUSION: Patients with FND did not have stronger placebo responses than healthy controls. The notion of generally increased suggestibility or increased suggestibility to placebo in FND seems mistaken. Instead, occasional dramatic placebo responses may occur because functional symptoms are inherently more changeable than those due to organic disease

The effects of life stress and neural learning signals on fluid intelligence.

Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account