Tuberous Sclerosis Complex: mutations, functions and phenotypes

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in multiple organs and tissues. TSC is caused by mutations in either the TSC1 or TSC2 gene. We searched for mutations in both genes in a cohort of 490 patients diagnosed with or suspected of having TSC using a combination of denaturing gradient gel electrophoresis, single-strand conformational polymorphism, direct sequencing, fluorescent in situ hybridisation and Southern blotting. We identified pathogenic mutations in 362 patients, a mutation detection rate of 74%. Of these 362 patients, 276 had a definite clinical diagnosis of TSC and in these patients 235 mutations were identified, a mutation detection rate of 85%. The ratio of TSC2:TSC1 mutations was 3.4:1. In our cohort, both TSC1 mutations and mutations in familial TSC2 cases were associated with phenotypes less severe than de novo TSC2 mutations. Interestingly, consistent with other studies, the phenotypes of the patients in which no mutation was identified were, overall, less severe than those of patients with either a known TSC1 or TSC2 mutation

Stimulated emission and ultrafast carrier relaxation in InGaN multiple quantum wells

Stimulated emission (SE) was measured from two InGaN multiple quantum well (MQW) laser structures with different In compositions. SE threshold power densities (I_th) increased with increasing QW depth (x). Time-resolved differential transmission measurements mapped the carrier relaxation mechanisms and explained the dependence of I_th on x. Carriers are captured from the barriers to the QWs in < 1 ps, while carrier recombination rates increased with increasing x. For excitation above I_th an additional, fast relaxation mechanism appears due to the loss of carriers in the barriers through a cascaded refilling of the QW state undergoing SE. The increased material inhomogeneity with increasing x provides additional relaxation channels outside the cascaded refilling process, removing carriers from the SE process and increasing I_th.Comment: submitted to Appl. Phys. Let

The impact of alkali-ion intercalation on redox chemistry and mechanical deformations: Case study on intercalation of Li, Na, and K ions into FePO4 cathode

Batteries made of charge carriers from Earth-crust abundant materials (e.g., Na, K, and Mg) have received extensive attention as an alternative to Li-ion batteries for grid storage. However, a lack of understanding of the behavior of these larger ions in the electrode materials hinders the development of electrode structures suitable for these large ions. In this study, we investigate the impact of alkali ions (Li, Na, and K) on the redox chemistry and mechanical deformations of iron phosphate composite cathodes by using electrochemical techniques and in situ digital image correlation. Na-ion and Li-ion intercalation demonstrate a nearly linear correlation between electrochemical strains and the state of charge and discharge. The strain development shows nonlinear dependance on the state of charge and discharge for K ions. Strain rate calculations show that K ion intercalation results in a progressive increase in the strain rate for all cycles. Li and Na intercalation induce nearly constant strain rates with the exception of the first discharge cycle of Na intercalation. When the same amount of ions are inserted into the electrode, the electrode shows the lowest strain generation upon Li intercalation compared to larger alkali ions. Na and K ions induce similar volumetric changes in the electrode when the state of charge and discharge is around 30%. Although the electrode experiences larger absolute strain generation at the end of the discharge cycles upon Na intercalation, strain rates were found to be greater for K ions. Potential-dependent behaviors also demonstrate more sluggish redox reactions during K intercalation, compared to Li and Na. Our quantitative analysis suggests that the strain rate, rather than the absolute value of strain, is the critical factor in amorphization of the crystalline electrode

Label-Free Biosensing with High Selectivity in Complex Media using Microtoroidal Optical Resonators

Although label-free biosensors comprised of optical microcavities inherently possess the capability of resolving molecular interactions at individual level, this extreme sensitivity restricts their convenience for large scale applications by inducing vulnerability towards non-specific interactions that readily occur within complex media. Therefore, the use of optical microresonators for biosensing is mostly limited within strictly defined laboratory conditions, instead of field applications as early detection of cancer markers in blood, or identification of contamination in food. Here, we propose a novel surface modification strategy suitable for but not limited to optical microresonator based biosensors, enabling highly selective biosensing with considerable sensitivity as well. Using a robust, silane-based surface coating which is simultaneously protein resistant and bioconjugable, we demonstrate that it becomes possible to perform biosensing within complex media, without compromising the sensitivity or reliability of the measurement. Functionalized microtoroids are successfully shown to resist nonspecific interactions, while simultaneously being used as sensitive biological sensors. This strategy could pave the way for important applications in terms of extending the use of state-of-the-art biosensors for solving problems similar to the aforementioned

Inevitable manifestation of wiggles in the expansion of the late Universe

Using the fact that the comoving angular diameter distance to the last scattering surface is strictly constrained almost model independently, we show that, for any model agreeing with the standard $\Lambda$CDM model on its background dynamics at $z\sim0$ and size of the comoving sound horizon at last scattering, the deviations of the Hubble radius from the one of the standard $\Lambda$CDM model must be a member of the set of admissible wavelets. The family of models characterized by this framework also offers nontrivial oscillatory behaviours in various functions that define the kinematics of the Universe, even when the wavelets themselves are very simple. We also discuss the consequences of attributing these kinematics to, first, dark energy, and second, varying gravitational coupling strength. Utilizing some simplest wavelets, we demonstrate the competence of this framework in describing the baryon acoustic oscillation (BAO) data without any modifications to the agreement with cosmic microwave background measurements. This framework also provides a natural explanation for the bumps found in nonparametric observational reconstructions of the Hubble parameter and dark energy density as compensations of the dips suggested by some BAO data, and questions the physical reality of their existence. We note that utilizing this framework on top of the models that agree with both the cosmic microwave background and local $H_0$ measurements but are held back by BAO data, one may resurrect these models through the wiggly nature of wavelets that can naturally accommodate the BAO data. Finally, we also suggest narrowing the plausible set of admissible wavelets to further improve our framework by imposing conditions from expected kinematics of a viable cosmological model or first principle fundamental physics such as energy conditions.Comment: 16 pages, 4 figures; matches the version published in Physical Review

Epitaxial lateral overgrowth of a-plane GaN by metalorganic chemical vapor deposition

We report on epitaxial lateral overgrowth (ELO) of (112¯0) a-plane GaN by metalorganic chemical vapor deposition. Different growth rates of Ga- and N-polar wings together with wing tilt create a major obstacle for achieving a smooth, fully coalesced surface in ELOa-plane GaN. To address this issue a two-step growth method was employed to provide a large aspect ratio of height to width in the first growth step followed by enhanced lateral growth in the second by controlling the growth temperature. By this method, the average ratio of Ga- to N-polar wing growth rate has been reduced from 4–6 to 1.5–2, which consequently reduced the wing-tilt induced height difference between the two approaching wings at the coalescence front, thereby making their coalescence much easier. Transmission electron microscopy showed that the threading dislocation density in the wing regions was 1.0×108 cm−2, more than two orders of magnitude lower than that in the window regions (4.2×1010 cm−2). However, a relatively high density of basal stacking faults of 1.2×104 cm−1 was still present in the wing regions as compared to c -plane GaN, where they are rarely observed away from the substrate. Atomic force microscopy(AFM) measurements showed two orders of magnitude higher density of surface pits in the window than in the wing regions, which were considered to be terminated by dislocations (partial ones related to stacking faults and full ones) on the surface. The existence of basal stacking faults was also revealed by AFM measurements on the a-plane ELO sample after wet chemical etching in hot H3PO4∕H2SO4 (1:1). The extensions of Ga-polar wings near the meeting fronts were almost free of stacking faults. The improvement of crystalline quality in the overgrown layer by ELO was also verified by near field scanning optical microscopy and time-resolved photoluminescence measurements; the former showing strongly enhanced luminescence from the wing regions, and the latter indicating longer decay times (0.25 ns) compared to a standard a-plane GaN template (40 ps)

Ultrasensitive label-free microcavity biosensors with high selectivity

High quality factor whispering gallery mode microresonators have been recently shown to exhibit detection sensitivity of single molecule; however, the selectivity of these sensors among different types of analytes remains as an important issue, obscuring the broad applicability of optical microcavities. We demonstrate a surface modification strategy for fabrication of high selectivity and sensitivity microcavity biosensors in this study. © 2011 IEEE