The Active Bayesian Brain and the Rorschach Task

The Rorschach offers a unique and interesting paradigm from the perspective of the (Bayesian) brain. This contribution to the cross-disciplinary special issue considers the Rorschach from the perspective of perceptual inference in the brain and how it might inform subject-specific differences in perceptual synthesis. Before doing so, we provide a broad overview of active inference in its various manifestations. In brief, active inference supposes that our perceptions are the best hypothesis to explain sensory impressions. On a Bayesian account, the requisite belief updating rests sensitively upon the precision or confidence ascribed to sensory input, relative to prior beliefs about the causes of sensations. This focus - on the balance between sensory and prior precision - has been a useful construct in both cognitive science (e.g., as a formal explanation for attention) and neuropsychology (e.g., as a formal explanation for aberrant or false inference in hallucinations). In this setting, false inference is generally understood as abnormally high precision afforded to high-level hypotheses or explanations for visual input, which may compensate for a failure to attenuate sensory precision. On this view, the Rorschach offers an interesting paradigm because the amount of precise information about the causes of visual input is deliberately minimized - and rendered ambiguous - thereby placing greater emphasis on prior beliefs entertained by the respondent. We close by exploring this issue and several other areas of intersection between Rorschach responding and active inference

Genome-wide methylome analysis using MethylCap-seq uncovers 4 hypermethylated markers with high sensitivity for both adeno- and squamous-cell cervical carcinoma

Background: Cytology-based screening methods for cervical adenocarcinoma (ADC) and to a lesser extent squamous-cell carcinoma (SCC) suffer from low sensitivity. DNA hypermethylation analysis in cervical scrapings may improve detection of SCC, but few methylation markers have been described for ADC. We aimed to identify novel methylation markers for the early detection of both ADC and SCC. Results: Genome-wide methylation profiling for 20 normal cervices, 6 ADC and 6 SCC using MethylCap-seq yielded 53 candidate regions hypermethylated in both ADC and SCC. Verification and independent validation of the 15 most significant regions revealed 5 markers with differential methylation between 17 normals and 13 cancers. Quantitative methylation-specific PCR on cervical cancer scrapings resulted in detection rates ranging between 80% and 92% while between 94% and 99% of control scrapings tested negative. Four markers (SLC6A5, SOX1, SOX14 and TBX20) detected ADC and SCC with similar sensitivity. In scrapings from women referred with an abnormal smear (n = 229), CIN3+ sensitivity was between 36% and 71%, while between 71% and 93% of adenocarcinoma in situ (AdCIS) were detected; and CIN0/1 specificity was between 88% and 98%. Compared to hrHPV, the combination SOX1/SOX14 showed a similar CIN3+ sensitivity (80% vs. 75%, respectively, P>0.2), while specificity improved (42% vs. 84%, respectively, P < 10(-5)). Conclusion: SOX1 and SOX14 are methylation biomarkers applicable for screening of all cervical cancer types

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Variations in 24-mu m morphologies among galaxies in the Spitzer Infrared Nearby Galaxies Survey: new insights into the Hubble sequence

To study the distribution of star formation and dust emission within nearby galaxies, we measured five morphological parameters in the 3.6- and 24-μm wavebands for 65 galaxies in the Spitzer Infrared Nearby Galaxies Survey (SINGS) and eight galaxies that were serendipitously observed by SINGS. The morphological parameters demonstrate strong variations along the Hubble sequence, including statistically significant differences between S0/a-Sab and Sc-Sd galaxies. Early-type galaxies are generally found to be compact, centralized, symmetric sources in the 24-μm band, while late-type galaxies are generally found to be extended, asymmetric sources. These results suggest that the processes that increase the real or apparent sizes of galaxies\u27 bulges also lead to more centralized 24-μm dust emission. Several phenomena, such as strong nuclear star formation, Seyfert activity, or outer ring structures, may cause galaxies to deviate from the general morphological trends observed at 24 μm. We also note that the 24-μm morphologies of Sdm-Im galaxies are quite varied, with some objects appearing very compact and symmetric but others appearing diffuse and asymmetric. These variations reflect the wide variation in star formation in irregular galaxies as observed at other wavelengths. The variations in the 24-μm morphological parameters across the Hubble sequence mirror many of the morphological trends seen in other tracers of the ISM and in stellar emission. However, the 24-μm morphological parameters for the galaxies in this sample do not match the morphological parameters measured in the stellar wavebands. This implies that the distribution of dust emission is related to but not equivalent to the distribution of stellar emission

Inter- and intra-observer agreement of BI-RADS-based subjective visual estimation of amount of fibroglandular breast tissue with magnetic resonance imaging: comparison to automated quantitative assessment.

PURPOSE: To evaluate the inter-/intra-observer agreement of BI-RADS-based subjective visual estimation of the amount of fibroglandular tissue (FGT) with magnetic resonance imaging (MRI), and to investigate whether FGT assessment benefits from an automated, observer-independent, quantitative MRI measurement by comparing both approaches. MATERIALS AND METHODS: Eighty women with no imaging abnormalities (BI-RADS 1 and 2) were included in this institutional review board (IRB)-approved prospective study. All women underwent un-enhanced breast MRI. Four radiologists independently assessed FGT with MRI by subjective visual estimation according to BI-RADS. Automated observer-independent quantitative measurement of FGT with MRI was performed using a previously described measurement system. Inter-/intra-observer agreements of qualitative and quantitative FGT measurements were assessed using Cohen's kappa (k). RESULTS: Inexperienced readers achieved moderate inter-/intra-observer agreement and experienced readers a substantial inter- and perfect intra-observer agreement for subjective visual estimation of FGT. Practice and experience reduced observer-dependency. Automated observer-independent quantitative measurement of FGT was successfully performed and revealed only fair to moderate agreement (k = 0.209-0.497) with subjective visual estimations of FGT. CONCLUSION: Subjective visual estimation of FGT with MRI shows moderate intra-/inter-observer agreement, which can be improved by practice and experience. Automated observer-independent quantitative measurements of FGT are necessary to allow a standardized risk evaluation. KEY POINTS: • Subjective FGT estimation with MRI shows moderate intra-/inter-observer agreement in inexperienced readers. • Inter-observer agreement can be improved by practice and experience. • Automated observer-independent quantitative measurements can provide reliable and standardized assessment of FGT with MRI

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

Super-resolving phase measurements with a multi-photon entangled state

Using a linear optical elements and post-selection, we construct an entangled polarization state of three photons in the same spatial mode. This state is analogous to a ``photon-number path entangled state'' and can be used for super-resolving interferometry. Measuring a birefringent phase shift, we demonstrate two- and three-fold improvements in phase resolution.Comment: 4 pages, 3 figure

Skeletal muscle ATP synthesis and cellular H+ handling measured by localized 31P-MRS during exercise and recovery

31P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H+) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60–75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP-model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism