Consciousness science : real progress and lingering misconceptions.

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Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.

Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes

Excitonic effects on coherent phonon dynamics in single wall carbon nanotubes

We discuss how excitons can affect the generation of coherent radial breathing modes in ultrafast spectroscopy of single wall carbon nanotubes. Photoexcited excitons can be localized spatially and give rise to a spatially distributed driving force in real space which involves many phonon wavevectors of the exciton-phonon interaction. The equation of motion for the coherent phonons is modeled phenomenologically by the Klein-Gordon equation, which we solve for the oscillation amplitudes as a function of space and time. By averaging the calculated amplitudes per nanotube length, we obtain time-dependent coherent phonon amplitudes that resemble the homogeneous oscillations that are observed in some pump-probe experiments. We interpret this result to mean that the experiments are only able to see a spatial average of coherent phonon oscillations over the wavelength of light in carbon nanotubes and the microscopic details are averaged out. Our interpretation is justified by calculating the time-dependent absorption spectra resulting from the macroscopic atomic displacements induced by the coherent phonon oscillations. The calculated coherent phonon spectra including excitonic effects show the experimentally observed symmetric peaks at the nanotube transition energies in contrast to the asymmetric peaks that would be obtained if excitonic effects were not included.Comment: submitted to Phys. Rev. B on 7 May 2013, revised on 17 July and 13 August 2013, published 30 August 201

The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

Mars rover sample return: An exobiology science scenario

A mission designed to collect and return samples from Mars will provide information regarding its composition, history, and evolution. At the same time, a sample return mission generates a technical challenge. Sophisticated, semi-autonomous, robotic spacecraft systems must be developed in order to carry out complex operations at the surface of a very distant planet. An interdisciplinary effort was conducted to consider how much a Mars mission can be realistically structured to maximize the planetary science return. The focus was to concentrate on a particular set of scientific objectives (exobiology), to determine the instrumentation and analyses required to search for biological signatures, and to evaluate what analyses and decision making can be effectively performed by the rover in order to minimize the overhead of constant communication between Mars and the Earth. Investigations were also begun in the area of machine vision to determine whether layered sedimentary structures can be recognized autonomously, and preliminary results are encouraging

Effect of different warm-up strategies on simulated laparoscopy performance: a randomized controlled trial.

OBJECTIVE: The objective of this trial was to assess which type of warm-up has the highest effect on virtual reality (VR) laparoscopy performance. The following warm-up strategies were applied: a hands-on exercise (group 1), a cognitive exercise (group 2), and no warm-up (control, group 3). DESIGN: This is a 3-arm randomized controlled trial. SETTING: The trial was conducted at the department of surgery of the University Hospital Basel in Switzerland. PARTICIPANTS: A total of 94 participants, all laypersons without any surgical or VR experience, completed the study. RESULTS: A total of 96 participants were randomized, 31 to group 1, 31 to group 2, and 32 to group 3. There were 2 postrandomization exclusions. In the multivariate analysis, we found no evidence that the intervention had an effect on VR performance as represented by 6 calculated subscores of accuracy, time, and path length for (1) camera manipulation and (2) hand-eye coordination combined with 2-handed maneuvers (p = 0.795). Neither the comparison of the average of the intervention groups (groups 1 and 2) vs control (group 3) nor the pairwise comparisons revealed any significant differences in VR performance, neither multivariate nor univariate. VR performance improved with increasing performance score in the cognitive exercise warm-up (iPad 3D puzzle) for accuracy, time, and path length in the camera navigation task. CONCLUSIONS: We were unable to show an effect of the 2 tested warm-up strategies on VR performance in laypersons. We are currently designing a follow-up study including surgeons rather than laypersons with a longer warm-up exercise, which is more closely related to the final task

Interstellar Extinction Law in the J, H, and Ks Bands toward the Galactic Center

We have determined the ratios of total to selective extinction in the near-infrared bands (J, H, Ks) toward the Galactic center from the observations of the region |l| < 2.0deg and 0.5deg < |b| < 1.0deg with the IRSF telescope and the SIRIUS camera. Using the positions of red clump stars in color-magnitude diagrams as a tracer of the extinction and reddening, we determine the average of the ratios of total to selective extinction to be A(Ks)/E(H-Ks) = 1.44+-0.01, A(Ks)/E(J-Ks) = 0.494+-0.006, and A(H)/E(J-H) = 1.42+-0.02, which are significantly smaller than those obtained in previous studies. From these ratios, we estimate that A(J) : A(H) : A(Ks) = 1 : 0.573+-0.009 : 0.331+-0.004 and E(J-H)/E(H-Ks) = 1.72+-0.04, and we find that the power law A(lambda) \propto lambda^{-1.99+-0.02} is a good approximation over these wavelengths. Moreover, we find a small variation in A(Ks)/E(H-Ks) across our survey. This suggests that the infrared extinction law changes from one line of sight to another, and the so-called ``universality'' does not necessarily hold in the infrared wavelengths.Comment: 18 pages, 9 figures, Accepted for publication in the Ap