What Turing Did after He Invented the Universal Turing Machine

Alan Turing anticipated many areas of current research incomputer and cognitive science. This article outlines his contributionsto Artificial Intelligence, connectionism, hypercomputation, andArtificial Life, and also describes Turing's pioneering role in thedevelopment of electronic stored-program digital computers. It locatesthe origins of Artificial Intelligence in postwar Britain. It examinesthe intellectual connections between the work of Turing and ofWittgenstein in respect of their views on cognition, on machineintelligence, and on the relation between provability and truth. Wecriticise widespread and influential misunderstandings of theChurch–Turing thesis and of the halting theorem. We also explore theidea of hypercomputation, outlining a number of notional machines thatcompute the uncomputable.     

The effect of changing excitation frequency on parallel conductance in different sized hearts

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.     

Ultrastructural features of diffuse malignant mesotheliomas

The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.     

Characterization of the native and recombinant catalytic subunit of human DNA polymerase gamma: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity

The human DNA polymerase gamma catalytic subunit was overexpressed in recombinant baculovirus-infected insect cells, and the 136 000 Da protein was purified to homogeneity. Application of the same purification protocol to HeLa mitochondrial lysates permitted isolation of native DNA polymerase gamma as a single subunit, allowing direct comparison of the native and recombinant enzymes without interference of other polypeptides. Both forms exhibited identical properties, and the DNA polymerase and 3' --> 5' exonuclease activities were shown unambiguously to reside in the catalytic polypeptide. The salt sensitivity and moderate processivity of the isolated catalytic subunit suggest other factors could be required to restore the salt tolerance and highly processive DNA synthesis typical of gamma polymerases. To facilitate our understanding of mitochondrial DNA replication and mutagenesis as well as cytotoxicity mediated by antiviral nucleotide analogues, we also constructed two site-directed mutant proteins of the human DNA polymerase gamma. Substituting alanine for two essential acidic residues in the exonuclease motif selectively eliminated the 3' --> 5' exonucleolytic function of the purified mutant polymerase gamma. Replacement of a tyrosine residue critical for sugar recognition with phenylalanine in polymerase motif B reduced dideoxynucleotide inhibition by a factor of 5000 with only minor effects on overall polymerase function.     

Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway

The NMDA receptor antagonistic effects of budipine were assessed using concentration- and patch-clamp techniques on cultured striatal, hippocampal, cortical and superior colliculus neurones. Inward current responses of striatal neurones to NMDA (200 microM) at -70 mV were antagonized by budipine in a concentration-dependent manner (50% inhibitory concentration (IC50) 59.4 +/- 10.7 microM, n = 17) with 24 times lower potency than memantine but similar potency to amantadine. In striatal neurones, budipine blocked outward currents at +70 mV with an IC50 of 827 microM, suggesting that the binding site is less deep in the channel (delta = 0.45) than for memantine. However, more detailed analysis of the fractional block by budipine 300 microM in hippocampal neurones gave a delta-value of 0.90, but revealed that 28% block is mediated at a voltage-independent site. This voltage-insensitive site was accessible in the absence of agonist. Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)). Calculation of the ratio kappa(off)/kappa(on) revealed an apparent Kd value of 88.7 microM. Budipine, memantine and amantadine had similar effects against NMDA-induced currents in cultured hippocampal, cortical and superior colliculus neurones, although amantadine was somewhat more potent in cultured striatal neurones. The relevance of NMDA receptor antagonism to the anti-Parkinsonian effects of budipine remains to be established.     

Synthesis and biological activity of novel thiazolidinediones

Novel compounds having a dual pharmacophore were synthesised and evaluated for their insulin sensitiser and anti-inflammatory properties in different animal models.     

Plasma osmolality and brain water content in a rat glioma model

Little is known about how intravenous fluids influence peritumoral edema formation. This experiment was designed to determine, in a rat glioma model, whether changes in plasma osmolality alter water content, as assessed by specific gravity (SpGr), in normal and neoplastic cerebral tissue. Cells cultured from an ethylnitrosourea-induced rat glioma were stereotactically implanted into the right striatum of Fischer 344 rats. A tumor growth interval of 21 days was allowed. In a second experiment, rats underwent a 60-second cortical freeze injury followed by 24 hours' recovery. In both experiments, rats were assigned to one of three groups: hypotonic (100 ml/kg of 0.2 mol/L NaCl in H2O, intraperitoneally; resultant plasma osmolality approximately 268 mOsm/kg); isotonic (no treatment; plasma osmolality approximately 298 mOsm/kg); or hypertonic (10 ml/kg of 1.0 mol/L NaCl in H2O, intraperitoneally; plasma osmolality approximately 342 mOsm/kg). Thirty minutes after fluid injection, regional SpGr was determined using a kerosene-bromobenzene gradient. In subsets of rats, the tissue morphology and blood-brain barrier permeability of Evans blue dye were assessed. Tissue within the freeze lesion was stained by Evans blue dye with sharp demarcation. Evans blue dye did not stain gliomatous tissue, and central necrosis was not histologically evident. In isotonic rats, glioma SpGr was reduced (1.0411 +/- 0.0012 g/ml) relative to the contralateral striatum (1.0437 +/- 0.0008 g/ml; P < 0.001). Despite this, a strong linear relation was observed for SpGr and plasma osmolality in both neoplastic and normal tissue. Within the freeze lesion in isotonic rats, SpGr was severely reduced (1.0335 +/- 0.0008 g/ml; P < 0.0001) compared with contralateral frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)