The Most Severe Test for Hydrophobicity Scales: Two Proteins with 88% Sequence Identity but Different Structure and Function

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. In their classic paper Kyte and Doolittle (KD) concluded that the "simplicity and graphic nature of hydrophobicity scales make them very useful tools for the evaluation of protein structures". In practice, however, attempts to develop hydrophobicity scales (for example, compatible with classical force fields (CFF) in calculating the energetics of protein folding) have encountered many difficulties. Here we suggest an entirely different approach, based on the idea that proteins are self-organized networks, subject to finite-scale criticality (like some network glasses). We test this proposal against two small proteins that are delicately balanced between alpha and alpha/beta structures, with different functions encoded with only 12% of their amino acids. This example explains why protein structure prediction is so challenging, and it provides a severe test for the accuracy and content of hydrophobicity scales. The new method confirms KD's evaluation, and at the same time suggests that protein structure, dynamics and function can be best discussed without using CFF

Effectors of hemoglobin. Separation of allosteric and affinity factors

The relative contributions of the allosteric and affinity factors toward the change in p50 have been calculated for a series of effectors of hemoglobin (Hb). Shifts in the ligand affinity of deoxy Hb and the values for 50% ligand saturation (p50) were obtained from oxygen equilibrium data. Because the high-affinity parameters (liganded conformation) are poorly determined from the equilibrium curves, they were determined from kinetic measurements of the association and dissociation rates with CO as ligand. The CO on-rates were obtained by flash photolysis measurements. The off-rates were determined from the rate of oxidation of HbCO by ferricyanide, or by replacement of CO with NO. The partition function of fully liganded hemoglobin for oxygen and CO is only slightly changed by the effectors. Measurements were made in the presence of the effectors 2,3-diphosphoglycerate (DPG), inositol hexakisphosphate (IHP), bezafibrate (Bzf), and two recently synthesized derivatives of Bzf (LR16 and L35). Values of p50 change by over a factor of 60; the on-rates decrease by nearly a factor of 8, with little change in the off-rates for the liganded conformation. The data indicate that both allosteric and affinity parameters are changed by the effectors; the changes in ligand affinity represent the larger contribution toward shifts in p50

Counting topological manifolds

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32762/1/0000133.pd

Suicide Attacks or "Martyrdom Operations" in Contemporary Jihad Literature

Martyrdom operations are a factor in contemporary radical Islam. These operations have their roots in classical jihad literature, but fundamentally are a by-product of widespread frustration and perceived humiliations on the part of Muslims. The attacks of 11 September 2001 are rooted within this tradition

Syzygies in equivariant cohomology for non-abelian Lie groups

We extend the work of Allday-Franz-Puppe on syzygies in equivariant cohomology from tori to arbitrary compact connected Lie groups G. In particular, we show that for a compact orientable G-manifold X the analogue of the Chang-Skjelbred sequence is exact if and only if the equivariant cohomology of X is reflexive, if and only if the equivariant Poincare pairing for X is perfect. Along the way we establish that the equivariant cohomology modules arising from the orbit filtration of X are Cohen-Macaulay. We allow singular spaces and introduce a Cartan model for their equivariant cohomology. We also develop a criterion for the finiteness of the number of infinitesimal orbit types of a G-manifold.Comment: 28 pages; minor change

Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

Objective: To quantify the periventricular venous density in neuromyelitis optica spectrum disease (NMOSD) in comparison to that in patients with multiple sclerosis (MS) and healthy control subjects. Materials and methods: Sixteen patients with NMOSD, 16 patients with MS and 16 healthy control subjects underwent 7.0-Tesla (7T) MRI. The imaging protocol included T2*-weighted (T2*w) fast low angle-shot (FLASH) and fluid-attenuated inversion recovery (FLAIR) sequences. The periventricular venous area (PVA) was manually determined by a blinded investigator in order to estimate the periventricular venous density in a region of interest-based approach. Results: No significant differences in periventricular venous density indicated by PVA were detectable in NMOSD versus healthy controls (p = 0.226). In contrast, PVA was significantly reduced in MS patients compared to healthy controls (p = 0.013). Conclusion: Unlike patients with MS, those suffering from NMOSD did not show reduced venous visibility. This finding may underscore primary and secondary pathophysiological differences between these two distinct diseases of the central nervous system

Determination and optimisation of Resonant Acoustic Mixing (RAM) efficiency in Polymer Bonded eXplosive (PBX) processing

An investigation into how the efficiency (time and energy required for homogeneity) of Resonant Acoustic Mixing (RAM) can be determined and optimised was undertaken. An idealised Polymer Bonded eXplosive (PBX) simulant based on glass microbeads (28.3 um D50, 62% v/v in binder and plasticiser) was used for mixing. Mixing evolution was monitored using machine output data, whereby the mixer ‘intensity’ (related to power draw) was plotted against time. Experiments were undertaken with three acceleration settings, three mixer units, and three vessel materials of low, medium, and high surface free energy. Different stages of the mixer ‘intensity’ profiles were found to correspond to discrete stages of mixing, as well as further rheological changes due to continued frictional heating, thus viscosity reduction, beyond homogeneity being achieved. Time to mixing completion was found to be repeatable within a standard deviation of +/- 10%, strongly dependent on acceleration setting, and additionally dependent on vessel material, though additional data is required to confirm this. A significant difference in mixing time was observed between different LabRAM units. Partial vacuum application without degassing was beneficial for mixing. Finally, a paradigm linking the ‘movement modes’ of mixing was constructed, based on literature observations and the experimental results

MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T

OBJECTIVE: To characterize paramagnetic MRI phase signal abnormalities in neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions in a cross-sectional study. METHODS: Ten patients with NMOSD and 10 patients with relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*-weighted imaging and supratentorial susceptibility weighted imaging. Next, we analyzed intra- and perilesional paramagnetic phase changes on susceptibility weighted imaging filtered magnetic resonance phase images. RESULTS: We frequently observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232 lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim-like phase changes: 2 of 112 lesions, 2%, p < 0.001; nodular phase changes: 2 of 112 lesions, 2%, p < 0.001). CONCLUSIONS: Rim-like or nodular paramagnetic MRI phase changes are characteristic for MS lesions and not frequently detectable in NMOSD. Future prospective studies should ask whether these imaging findings can be used as a biomarker to distinguish between NMOSD- and MS-related brain lesions