Numerical and Theoretical Study of a Monodisperse Hard-Sphere Glass Former

There exists a variety of theories of the glass transition and many more numerical models. But because the models need built-in complexity to prevent crystallization, comparisons with theory can be difficult. We study the dynamics of a deeply supersaturated \emph{monodisperse} four-dimensional (4D) hard-sphere fluid, which has no such complexity, but whose strong intrinsic geometrical frustration inhibits crystallization, even when deeply supersaturated. As an application, we compare its behavior to the mode-coupling theory (MCT) of glass formation. We find MCT to describe this system better than any other structural glass formers in lower dimensions. The reduction in dynamical heterogeneity in 4D suggested by a milder violation of the Stokes-Einstein relation could explain the agreement. These results are consistent with a mean-field scenario of the glass transition.Comment: 5 pages, 3 figure

The influence of knee rigidity on balance corrections: a comparison with responses of cerebellar ataxia patients

Knee rigidity due to aging or disease is associated with falls. A causal relationship between instability and knee rigidity has not been established. Here, we examined whether insufficient knee movement due to knee rigidity could underlie poor balance control in patients. We addressed this by examining the effect of artificially "locking” the knees on balance control in 18 healthy subjects, tested with and without individually fitted knee casts on both legs. Subjects were exposed to sudden rotations of a support surface in six different directions. The primary outcome measure was body centre of mass (COM) movement, and secondary outcome measures included biomechanical responses of the legs, pelvis and trunk. Knee casts caused increased backward COM movement for backward perturbations and decreased vertical COM movement for forward perturbations, and caused little change in lateral COM movement. At the ankles, dorsiflexion was reduced for backward perturbations. With knee casts, there was less uphill hip flexion and more downhill hip flexion. A major difference with knee casts was a reversed pelvis pitch movement and an increased forward trunk motion. These alterations in pitch movement strategies and COM displacements were similar to those we have observed previously in patients with knee rigidity, specifically those with spinocerebellar ataxia (SCA). Pelvis roll and uphill arm abduction were also increased with the casts. This roll movement strategy and minor changes in lateral COM movement were not similar to observations in patients. We conclude that artificial knee rigidity increases instability, as reflected by greater posterior COM displacement following support surface tilts. Healthy controls with knee casts used a pitch movement strategy similar to that of SCA patients to offset their lack of knee movement in regaining balance following multidirectional perturbations. This similarity suggests that reduced knee movements due to knee rigidity may contribute to sagittal plane postural instability in SCA patients and possibly in other patient groups. However in the roll plane, healthy controls rapidly compensate by adjusting arm movements and hip flexion to offset the effects of knee rigidit

Geometrical Frustration: A Study of 4d Hard Spheres

The smallest maximum kissing-number Voronoi polyhedron of 3d spheres is the icosahedron and the tetrahedron is the smallest volume that can show up in Delaunay tessalation. No periodic lattice is consistent with either and hence these dense packings are geometrically frustrated. Because icosahedra can be assembled from almost perfect tetrahedra, the terms "icosahedral" and "polytetrahedral" packing are often used interchangeably, which leaves the true origin of geometric frustration unclear. Here we report a computational study of freezing of 4d hard spheres, where the densest Voronoi cluster is compatible with the symmetry of the densest crystal, while polytetrahedral order is not. We observe that, under otherwise comparable conditions, crystal nucleation in 4d is less facile than in 3d. This suggest that it is the geometrical frustration of polytetrahedral structures that inhibits crystallization.Comment: 4 pages, 3 figures; revised interpretatio

Foveal Densifometry in Retinitis Pigmentosa

Cone density and psychophysical thresholds were investigated in patients with retinitis pigmentosa. Our aim was to assess possible disturbances of foveal cones, especially in patients with good visual acuity. Using the continuously recording densitometer described by van Norren and van der Kraats, we examined ten patients (19 eyes). With the same apparatus it was possible to determine cone final threshold. In all patients double density values were lower than in an age-matched and sex-matched control group of an equal number, and the half time of regeneration was increased in eight eyes. In 12 eyes of eight patients the foveal final threshold was raised above normal. Pseudoprotanomaly was found in seven eyes in four males. Possible explanations for these findings are discussed. Since reduced double density was found in all patients with retinitis pigmentosa, we conclude that disturbed foveal cones are probably a common and rather early feature in this disease. Invest Ophthalmol Vis Sci 24: [1123][1124][1125][1126][1127][1128][1129][1130] 1983 Retinitis pigmentosa is a progressive form of tapetoretinal dystrophy. Typical observations in the disease are the characteristic fundus picture of bone-spicule pigmentation, a lowered or undetectable scotopic b-wave on electrophysiologic examination, an annular scotoma on perimetric examination, and a raised final threshold on examination with the Goldmann-Weekers adaptometer. The disease affects primarily the receptor layer, particularly the cells of the midperipheral retina; in a later stage the cones in the fovea may also become involved. It is well known that the central field of vision may be retained for a long time and that the visual acuity can remain relativily unimpaired, even in the far advanced stages of the disease. When the technique of retinal densitometry came into use, it was to be expected that attention would be especially focused on measuring the properties of the rods, and several investigators demonstrated that a reduction in the density of rhodopsin correlated well with the loss of visual sensitivity. 1 -2 Perlman and Auerbach 3 distinguished two groups of patients: one group with a recessive inheritance, in which the relation between the log threshold elevation and the fraction of rhodopsin was probably linear, and another group with principally dominant inheritance in which absolute threshold elevation was linearly related to the fraction of rhodopsin present. It was our aim to investigate more thoroughly whether densitometric examination could demonstrate an impaired function in foveal cones in patients with retinitis pigmentosa. For this purpose we used the retinal densitometer described by van Norren and van der Kraats, 4 an instrument that enables reliable and relatively easy measurements in patients. To assess the functional state of the fovea, we measured psychophysical cone dark adaptation to all patients with the same apparatus. Our findings show that in all patients tested by densitometry, the double density values were significantly less than normal, and that in several of these subjects the half-time of pigment regeneration was slower than in the normal. Materials and Methods Subjects For the patient group only those patients were selected who had a confirmed retinitis pigmentosa, established by the following criteria. Except for patients 1 and 2, all patients had a family history of retinitis pigmentosa. Patient 5 is a sister of patient 6, patient 4 and 8 are brothers, and patient 9 and 10 are brother

Hard sphere crystallization gets rarer with increasing dimension

We recently found that crystallization of monodisperse hard spheres from the bulk fluid faces a much higher free energy barrier in four than in three dimensions at equivalent supersaturation, due to the increased geometrical frustration between the simplex-based fluid order and the crystal [J.A. van Meel, D. Frenkel, and P. Charbonneau, Phys. Rev. E 79, 030201(R) (2009)]. Here, we analyze the microscopic contributions to the fluid-crystal interfacial free energy to understand how the barrier to crystallization changes with dimension. We find the barrier to grow with dimension and we identify the role of polydispersity in preventing crystal formation. The increased fluid stability allows us to study the jamming behavior in four, five, and six dimensions and compare our observations with two recent theories [C. Song, P. Wang, and H. A. Makse, Nature 453, 629 (2008); G. Parisi and F. Zamponi, Rev. Mod. Phys, in press (2009)].Comment: 15 pages, 5 figure

Harvesting graphics power for MD simulations

We discuss an implementation of molecular dynamics (MD) simulations on a graphic processing unit (GPU) in the NVIDIA CUDA language. We tested our code on a modern GPU, the NVIDIA GeForce 8800 GTX. Results for two MD algorithms suitable for short-ranged and long-ranged interactions, and a congruential shift random number generator are presented. The performance of the GPU's is compared to their main processor counterpart. We achieve speedups of up to 80, 40 and 150 fold, respectively. With newest generation of GPU's one can run standard MD simulations at 10^7 flops/$.Comment: 12 pages, 5 figures. Submitted to Mol. Si

Maternal hemoglobin and iron status in early pregnancy and risk of respiratory tract infections in childhood:A population-based prospective cohort study

Background: Maternal hemoglobin and iron status measures during pregnancy might affect the developing fetal respiratory system leading to adverse respiratory conditions. Our aim was to assess the associations of maternal hemoglobin and iron status measures during pregnancy with the risk of respiratory tract infections in children until 10 years of age. Methods:In a population-based cohort study among 5134 mother–child pairs, maternal hemoglobin and iron status including ferritin, transferrin, and transferrin saturation were measured during early pregnancy. In children, physician-attended respiratory tract infections from age 6 months until 10 years were assessed by questionnaires. Confounder-adjusted generalized estimating equation modeling was applied. Results: After taking multiple testing into account, high maternal ferritin concentrations and low maternal transferrin saturation during pregnancy were associated with an overall increased risk of upper, not lower, respiratory tract infections until age 10 years of the child [OR (95% CI: 1.23 (1.10, 1.38) and 1.28 (1.12, 1.47), respectively)]. High maternal transferrin saturation during pregnancy was associated with a decreased and increased risk of upper respiratory tract infections at 1 and 6 years, respectively, [OR (95% CI: 0.60 (0.44, 0.83) and 1.54 (1.17, 2.02))]. Observed associations were suggested to be U-shaped (p-values for non-linearity ≤.001). Maternal hemoglobin and iron status measures during pregnancy were not consistently associated with child's gastroenteritis and urinary tract infections, as proxies for general infection effects. Conclusion: High maternal ferritin and low transferrin saturation concentrations during early pregnancy were most consistently associated with an overall increased risk of child's upper, not lower, respiratory tract infections.</p

Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype

BACKGROUND: Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to its cognate transfer RNA and therefore plays an essential role in protein biosynthesis. METHODS: We used exome sequencing, aminoacylation assays, homology modeling, and immuno-isolation of transfected MARS to identify and characterize mutations in the methionyl-tRNA synthetase gene (MARS) in an infant with an unexplained multi-organ phenotype. RESULTS: We identified compound heterozygous mutations (F370L and I523T) in highly conserved regions of MARS. The parents were each heterozygous for one of the mutations. Aminoacylation assays documented that the F370L and I523T MARS mutants had 18 ± 6% and 16 ± 6%, respectively, of wild-type activity. Homology modeling of the human MARS sequence with the structure of E. coli MARS showed that the F370L and I523T mutations are in close proximity to each other, with residue I523 located in the methionine binding pocket. We found that the F370L and I523T mutations did not affect the association of MARS with the multisynthetase complex. CONCLUSION: This infant expands the catalogue of inherited human diseases caused by mutations in aminoacyl-tRNA synthetase genes

Detection of Active Mammalian GH31 α-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes

The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. α-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the lysosomal acid α-glucosidase (GAA) causes the lysosomal glycogen storage disorder, Pompe disease. Here, we design a synthetic route for fluorescent and biotin-modified ABPs for in vitro and in situ monitoring of α-glucosidases. We show, through mass spectrometry, gel electrophoresis, and X-ray crystallography, that α-glucopyranose configured cyclophellitol aziridines label distinct retaining α-glucosidases including GAA and ER α-glucosidase II, and that this labeling can be tuned by pH. We illustrate a direct diagnostic application in Pompe disease patient cells, and discuss how the probes may be further exploited for diverse applications