71 research outputs found
Warren McCulloch and the British cyberneticians
Warren McCulloch was a significant influence on a number of British cyberneticians, as some British pioneers in this area were on him. He interacted regularly with most of the main figures on the British cybernetics scene, forming close friendships and collaborations with several, as well as mentoring others. Many of these interactions stemmed from a 1949 visit to London during which he gave the opening talk at the inaugural meeting of the Ratio Club, a gathering of brilliant, mainly young, British scientists working in areas related to cybernetics. This paper traces some of these relationships and interaction
Dynamic correlations in an ordered c(22) lattice gas
We obtain the dynamic correlation function of two-dimensional lattice gas
with nearest-neighbor repulsion in ordered c(22) phase
(antiferromagnetic ordering) under the condition of low concentration of
structural defects. It is shown that displacements of defects of the ordered
state are responsible for the particle number fluctuations in the probe area.
The corresponding set of kinetic equations is derived and solved in linear
approximation on the defect concentration. Three types of strongly correlated
complex jumps are considered and their contribution to fluctuations is
analysed. These are jumps of excess particles, vacancies and flip-flop jumps.
The kinetic approach is more general than the one based on diffusion-like
equations used in our previous papers. Thus, it becomes possible to adequately
describe correlations of fluctuations at small times, where our previous theory
fails to give correct results. Our new analytical results for fluctuations of
particle number in the probe area agree well with those obtained by Monte Carlo
simulations.Comment: 10 pages, 7 figure
Drug Screening Platform Using Human Induced Pluripotent Stem Cell-Derived Atrial Cardiomyocytes and Optical Mapping
Current drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell‐derived atrial and ventricular cardiomyocytes (hiPSC‐aCMs and hiPSC‐vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial‐selective compounds in vitro. We optimized differentiation of hiPSC‐aCMs by modulating the WNT and retinoid signaling pathways. Characterization of the transcriptome and proteome revealed that retinoic acid pushes the differentiation process into the atrial lineage and generated hiPSC‐aCMs. Functional characterization using optical mapping showed that hiPSC‐aCMs have shorter action potential durations and faster Ca2+ handling dynamics compared with hiPSC‐vCMs. Furthermore, pharmacological investigation of hiPSC‐aCMs captured atrial‐selective effects by displaying greater sensitivity to atrial‐selective compounds 4‐aminopyridine, AVE0118, UCL1684, and vernakalant when compared with hiPSC‐vCMs. These results established that a model system incorporating hiPSC‐aCMs combined with optical mapping is well‐suited for preclinical drug screening of novel and targeted atrial selective compounds
Abnormal cardiovascular sympathetic and parasympathetic responses to physical and emotional stimuli in depersonalization disorder
BACKGROUND: Depersonalization disorder (DPD) is characterized by a subjective sense of unreality, disembodiment, emotional numbing and reduced psychogenic (sudomotor) sympathoexcitation. AIMS: Three related experiments utilized escalating physical and emotional challenges in 14 DPD participants and 16 controls aimed to elucidate (i) whether the cardiovascular sympathetic (SNS) and parasympathetic (PNS) nervous systems are implicated in DPD pathophysiology and (ii) if possible, to determine whether the blunted sympathoexcitation in DPD is peripherally or centrally mediated. METHOD: Participants completed the Beck Anxiety Inventory (BAI), Dissociative Experience Scale (DES), and Cambridge Depersonalization Scale (CDS). Study I recorded heart rate (HR) and blood pressure (BP) during 5 min supine baseline, 3 min sustained handgrip (HG), 3 min cold pressor (CP) and 5 min 60° head-up tilt (HUT). In study II, HR, BP, and heart rate variability (HRV) were recorded during 5 min simultaneous 60° HUT and continuous presentation of unpleasant images (5 s per image). Study III examined HR and BP orienting responses (ORs) to simultaneous 60° HUT and pseudorandom presentation of unpleasant, neutral and pleasant images (5 s per image 3 min 25 s). OR data was grouped by image valence post hoc. RESULTS: DPD BAI (p = 0.0004), DES (p = 0.0002), and CDS (p ≤ 0.0001) scores were higher than controls. The DPD group produced diminished diastolic BP (DBP) (p = 0.045) increases to HG. Other indices were comparable between groups. DPD participants produced diminished systolic BP (SBP) (p = 0.003) and DBP (p = 0.002) increases, but greater (p = 0.004) HR increases to CP. In study II, DPD high frequency HRV (HF-HRV)-indicating parasympathetic vagal activity-was reduced (p = 0.029). In study III, DPD DBP was higher throughout the 5 s duration of HUT/pseudorandom unpleasant image presentation (1 s, p = 0.002, 2 s p = 0.033, 3 s p = 0.001, 4 s p = 0.009, 5 s p = 0.029). CONCLUSIONS: Study I's BP pressor data supports previous findings of suppressed sympathoexcitation in DPD. The greater HR increases to CP, decreased HF-HRV in study II, and increased DBP during unpleasant ORs in study III implicates the SNS and PNS in DPD pathophysiology. These studies suggest the cardiovascular autonomic dysregulation in DPD is likely to be centrally-mediated
Steering the future. The emergence of “Western” futures research and its production of expertise, 1950s to early 1970s
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