ALBERT

Description: Here, we present x-ray resonant magnetic dichroism and x-ray resonant magnetic scattering measurements of the temperature dependence of magnetism in Pr-doped La-Ca-Mn-O films grown on (110) NdGaO 3 substrates. We observed thermal hysteresis of the ferromagnetism in one film that also showed large thermal hysteresis of ∼18 K in transport measurements. While in a second film of a different nominal chemistry, which showed very small thermal hysteresis ∼3 K in transport measurements, no thermal hysteresis of the ferromagnetism was observed. These macroscopic properties are correlated with evolution of surface magnetization across metal insulator transition for these films as observed by soft x-ray resonant magnetic scattering measurements.

Description: Aims In recent years, coastal mangroves have been frequently affected by large disturbances (cyclones, hurricanes, flooding and tsunamis) and post-disturbance vegetation is often dominated by small stature mangrove, mangrove-associate and non-mangrove species potentially affecting ecosystem functioning. Knowledge on the processes of mangrove vegetation development and recovery (succession) following normal and large disturbances will benefit practitioners in designing robust ecosystem management/restoration plans. Here we propose a conceptual model of disturbance-mediated succession in mangroves. Methods Based on field observations and species’ life history traits, we develop conceptual models of mangrove succession under normal disturbance regime and recently experienced increased frequency of large disturbances. We evaluate our conceptual models by conducting a scenario testing experiment. Important Findings We suggest two predominant processes affecting mangrove succession after disturbance: propagule limitation due to damage of seed producing mature trees and dispersal barrier resulting from biological invasion associated with large disturbance. We argue that large disturbances affect mature trees more than the small-stature non-tree (shrubs, herbs and climbers) species creating a larger propagule shortage for mangrove tree species than non-tree species. Secondly, large disturbances facilitate invasion of free-floating aquatics, which may interfere with the flow-facilitated propagule dispersal and seedling establishment of mangrove species. In a scenario testing experiment, we have shown that similar levels of disturbance impact vegetation development and recovery differently depending on the presence or absence of invasive species. We conclude that since biological invasion is one of the major drivers of post-disturbance mangrove succession, the dimension of biological invasion should be included in prediction, management and restoration of mangrove forests.

Description: Single-nucleotide substitutions and small in-frame insertions or deletions identified in human breast cancer susceptibility genes BRCA1 and BRCA2 are frequently classified as variants of unknown clinical significance (VUS) due to the availability of very limited information about their functional consequences. Such variants can most reliably be classified as pathogenic or non-pathogenic based on the data of their co-segregation with breast cancer in affected families and/or their co-occurrence with a pathogenic mutation. Biological assays that examine the effect of variants on protein function can provide important information that can be used in conjunction with available familial data to determine the pathogenicity of VUS. In this report, we have used a previously described mouse embryonic stem (mES) cell-based functional assay to characterize eight BRCA2 VUS that affect highly conserved amino acid residues and map to the N-terminal PALB2-binding or the C-terminal DNA-binding domains. For several of these variants, very limited co-segregation information is available, making it difficult to determine their pathogenicity. Based on their ability to rescue the lethality of Brca2- deficient mES cells and their effect on sensitivity to DNA-damaging agents, homologous recombination and genomic integrity, we have classified these variants as pathogenic or non-pathogenic. In addition, we have used homology-based modeling as a predictive tool to assess the effect of some of these variants on the structural integrity of the C-terminal DNA-binding domain and also generated a knock-in mouse model to analyze the physiological significance of a residue reported to be essential for the interaction of BRCA2 with meiosis-specific recombinase, DMC1.

Description: Neuronal ceroid lipofuscinosis (NCL) comprises ~13 genetically distinct lysosomal disorders primarily affecting the central nervous system. Here we report successful reprograming of patient fibroblasts into induced pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation. CLN2/TPP1- and CLN3-iPSCs displayed overlapping but distinct biochemical and morphological abnormalities within the endosomal–lysosomal system. In neuronal derivatives, further abnormalities were observed in mitochondria, Golgi and endoplasmic reticulum. While lysosomal storage was undetectable in iPSCs, progressive disease subtype-specific storage material was evident upon neural differentiation and was rescued by reintroducing the non-mutated NCL proteins. In proof-of-concept studies, we further documented differential effects of potential small molecule TPP1 activity inducers. Fenofibrate and gemfibrozil, previously reported to induce TPP1 activity in control cells, failed to increase TPP1 activity in patient iPSC-derived neural progenitor cells. Conversely, nonsense suppression by PTC124 resulted in both an increase of TPP1 activity and attenuation of neuropathology in patient iPSC-derived neural progenitor cells. This study therefore documents the high value of this powerful new set of tools for improved drug screening and for investigating early mechanisms driving NCL pathogenesis.

Description: In this study, we have investigated the ion concentration dependent collective dynamics in two series of deep eutectic solvent (DES) systems by femtosecond Raman-induced Kerr effect spectroscopy, as well as some physical properties, e.g., shear viscosity ( η ), density ( ρ ), and surface tension ( γ ). The DES systems studied here are [0.75CH 3 CONH 2 + 0.25{ f  KSCN + (1 – f  )NaSCN}] and [0.78CH 3 CONH 2 + 0.22{ f  LiBr + (1 – f  )LiNO 3 }] with f = 0, 0.2, 0.4, 0.6, 0.8, and 1.0. γ of these DES systems shows near insensitivity to f , while ρ shows a moderate dependence on f . Interestingly, η exhibits a strong dependence on f . In the low-frequency Kerr spectra, obtained via the Fourier transform of the collected Kerr transients, a characteristic band at ∼70 cm −1 is clear in [0.78CH 3 CONH 2 + 0.22{ f  LiBr + (1 – f  )LiNO 3 }] DES especially at the larger f . The band is attributed to the intermolecular hydrogen bond of acetamide. Because of less depolarized Raman activities of intermolecular/interionic vibrational motions, which are mostly translational (collision-induced or interaction-induced) motions, of spherical ions, the intermolecular hydrogen-bonding band is clearly observed. In contrast, the intermolecular hydrogen-bonding band is buried in the other intermolecular/interionic vibrational motions, which includes translational and reorientational (librational) motions and their cross-terms, in [0.75CH 3 CONH 2 + 0.25{ f  KSCN + (1 – f  )NaSCN}] system. The first moment ( M 1 ) of the intermolecular/interionic vibrational band in these DES systems is much higher than that in typical neutral molecular liquids and shows a weak but contrasting dependence on the bulk parameter γ / ρ . The time constants for picosecond overdamped Kerr transients in both the DES systems, which are obtained on the basis of the analysis fitted by a triexponential function, are rather insensitive to f for both the DES systems, but all the three time constants (fast: ∼1–3 ps; intermediate: ∼7–20 ps; and slow: ∼100 ps) are different between the [0.78CH 3 CONH 2 + 0.22{ f  LiBr + (1 – f  )LiNO 3 }] and [0.75CH 3 CONH 2 + 0.25{ f  KSCN + (1 – f  )NaSCN}] systems. These results indicate that the intermolecular/interionic interactions in DES systems is strongly influenced by the ionic species present in these DES systems.

Description: Rugged energy landscapes find wide applications in diverse fields ranging from astrophysics to protein folding. We study the dependence of diffusion coefficient ( D ) of a Brownian particle on the distribution width (ɛ) of randomness in a Gaussian random landscape by simulations and theoretical analysis. We first show that the elegant expression of Zwanzig [Proc. Natl. Acad. Sci. U.S.A.85, 2029 (1988)] for D (ɛ) can be reproduced exactly by using the Rosenfeld diffusion-entropy scaling relation. Our simulations show that Zwanzig's expression overestimates D in an uncorrelated Gaussian random lattice – differing by almost an order of magnitude at moderately high ruggedness. The disparity originates from the presence of “three-site traps” (TST) on the landscape – which are formed by the presence of deep minima flanked by high barriers on either side. Using mean first passage time formalism, we derive a general expression for the effective diffusion coefficient in the presence of TST, that quantitatively reproduces the simulation results and which reduces to Zwanzig's form only in the limit of infinite spatial correlation. We construct a continuous Gaussian field with inherent correlation to establish the effect of spatial correlation on random walk. The presence of TSTs at large ruggedness (ɛ ≫ k B T ) gives rise to an apparent breakdown of ergodicity of the type often encountered in glassy liquids.

Description: A time dependent thermal model for a superconducting constriction based weak-link (WL) is discussed for investigating the deterministic dynamics of its temperature and phase. A new dynamic regime is found where a non-zero voltage exists across the WL, and its temperature stabilizes between the bath temperature and superconductor's critical temperature. This regime exists over a limited bias current range and gives rise to a new hysteretic regime in current-voltage characteristics. We also discuss the effect of fluctuations on the current-voltage characteristics and experimental implications of this dynamic regime.

Description: A semi-molecular theory for studying composition dependent Stokes shift dynamics of a dipolar solute in binary mixtures of (non-dipolar ionic liquid + common dipolar solvent) is developed here. The theory provides microscopic expressions for solvation response functions in terms of static and dynamic structure factors of the mixture components and solute-solvent static correlations. In addition, the theory provides a framework for examining the interrelationship between the time dependent solvation response in and frequency dependent dielectric relaxation of a binary mixture containing electrolyte. Subsequently, the theory has been applied to predict ionic liquid (IL) mole fraction dependent dynamic Stokes shift magnitude and solvation energy relaxation for a dipolar solute, C153, in binary mixtures of an ionic liquid, trihexyltetradecylphosphonium chloride ([P 14,666 ][Cl]) with a common dipolar solvent, methanol (MeOH). In the absence of suitable experimental data, necessary input parameters have been obtained from approximate methods. Dynamic shifts calculated for these mixtures exhibit a linear increase with IL mole fraction for the most part of the mixture composition, stressing the importance of solute-IL dipole-ion interaction. Average solvation rates, on the other hand, show a nonlinear IL mole fraction dependence which is qualitatively similar to what has been observed for such binary mixtures with imidazolium (dipolar) ILs. These predictions should be re-examined in suitable experiments.

Description: We propose a multivariate generalization of the univariate two-sample run test based on the shortest Hamiltonian path. The proposed test is distribution-free in finite samples. While most existing two-sample tests perform poorly or are even inapplicable to high-dimensional data, our test can be conveniently used in high-dimension, low-sample-size situations. We investigate its power when the sample size remains fixed and the dimension of the data grows to infinity. Simulated and real datasets demonstrate our method’s superiority over existing nonparametric two-sample tests.

Description: Understanding of metal insulator transitions in a strongly correlated system, driven by Anderson localization (disorder) and/or Mott localization (correlation), is a long standing problem in condensed matter physics. The prevailing fundamental question would be how these two mechanisms contrive to accomplish emergent anomalous behaviors. Here, we have grown high quality perovskite SrIrO 3 thin films, containing a strong spin orbit coupled 5 d element Ir, on various substrates such as GdScO 3 (110), DyScO 3 (110), SrTiO 3 (001), and NdGaO 3 (110) with increasing lattice mismatch, in order to carry out a systematic study on the transport properties. We found that metal insulator transitions can be induced in this system; by either reducing thickness (on best lattice matched substrate) or changing degree of lattice strain (by lattice mismatch between film and substrates) of films. Surprisingly these two pathways seek two distinct types of metal insulator transitions; the former falls into disorder driven Anderson type whereas the latter turns out to be of unconventional Mott-Anderson type with the interplay of disorder and correlation. More interestingly, in the metallic phases of SrIrO 3 , unusual non-Fermi liquid characteristics emerge in resistivity as Δ ρ ∝ T ε with ε evolving from 4/5 to 1 to 3/2 with increasing lattice strain. We discuss theoretical implications of these phenomena to shed light on the metal insulator transitions.