Extension of the Johnson-Mehl-Avrami-Kolmogorov theory incorporating anisotropic growth studied by Monte Carlo simulations

An analytical theory has been developed, based on Monte Carlo (MC) simulations, describing the kinetics of isothermal phase transformations proceeding by nucleation and subsequent growth for d-1 dimensional growth in d dimensional space (with d 2 or 3). This type of growth is of interest since it is generally anisotropic, leads to hard impingement, and obtains strong deviations from the traditional Johnson-Mehl-Avrami-Kolmogorov (JMAK) theory. Within the MC simulations 1D growth can occur with equal probability in two or three different nonparallel orientations in 2D space. In 3D space 2D growth can occur with equal probability in three (or two) different orthogonal orientations. The MC simulations show that initially always a regime is present where JMAK theory prevails, but that after a well-defined critical time a transition to a blocking regime occurs. Both regimes are characterized by clearly different, but nearly constant values of the Avrami exponent which depend on the dimensionality of growth and space and on the time dependence of nucleation. The dependence of the critical time and of the extended fraction within the blocking regime (based on the concept of the extended volume of the JMAK theory) on the nucleation and growth parameters has been extensively analyzed and all results of the MC simulations have been captured within the analytical theory

Aligned gold nanorods in silica made by ion irradiation of core-shell colloidal particles

Colloidal particles with a 14 nm diameter Au core surrounded by a 72 nm thick silica shell have been irradiated with 30 MeV heavy ions. The shell deforms into an oblate ellipsoid, while the core becomes rod-shaped (aspect ratio up to 9) with the major axis along the beam. Optical extinction measurements show evidence for split plasmon bands, characteristic for anisotropic metal nanoparticles

Ultrafast Ge-Te bond dynamics in a phase-change superlattice

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics mechanisms accompanying the out-of-equilibrium phases is still missing. Here, after overheating a phase-change chalcogenide superlattice by an ultrafast laser pulse, we indirectly track the lattice relaxation by time resolved x-ray absorption spectroscopy (tr-XAS) with a sub-ns time resolution. The approach to the tr-XAS experimental results reported in this work provides an atomistic insight of the mechanism that takes place during the cooling process; meanwhile a first-principles model mimicking the microscopic distortions accounts for a straightforward representation of the observed dynamics. Finally, we envisage that our approach can be applied in future studies addressing the role of dynamical structural strain in PCMs.M.M. acknowledges the support of the BACH beamline staff during the synchrotron experiments and Roberta Ciprian for insightful discussions. This work was supported by EU within FP7 project PASTRY [GA 317764]

Cone-rod dystrophy can be a manifestation of Danon disease

Background Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Methods Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Results Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fieldsdemonstrated central scotoma. The causal mutation was p. Gly384Arg in LAMP2; no mutations were found in RPGR. Conclusions This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

Infrared photovoltaic detector based on p-GeTe/n-Si heterojunction

GeTe is an important narrow bandgap semiconductor material and has found application in the fields of phase change storage as well as spintronics devices. However, it has not been studied for application in the field of infrared photovoltaic detectors working at room temperature. Herein, GeTe nanofilms were grown by magnetron sputtering technique and characterized to investigate its physical, electrical, and optical properties. A high-performance infrared photovoltaic detector based on GeTe/Si heterojunction with the detectivity of 8 × 1011 Jones at 850 nm light irradiation at room temperature was demonstrated

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents

S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio

Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry

Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus

Quantitative cardiovascular magnetic resonance for molecular imaging

Cardiovascular magnetic resonance (CMR) molecular imaging aims to identify and map the expression of important biomarkers on a cellular scale utilizing contrast agents that are specifically targeted to the biochemical signatures of disease and are capable of generating sufficient image contrast. In some cases, the contrast agents may be designed to carry a drug payload or to be sensitive to important physiological factors, such as pH, temperature or oxygenation. In this review, examples will be presented that utilize a number of different molecular imaging quantification techniques, including measuring signal changes, calculating the area of contrast enhancement, mapping relaxation time changes or direct detection of contrast agents through multi-nuclear imaging or spectroscopy. The clinical application of CMR molecular imaging could offer far reaching benefits to patient populations, including early detection of therapeutic response, localizing ruptured atherosclerotic plaques, stratifying patients based on biochemical disease markers, tissue-specific drug delivery, confirmation and quantification of end-organ drug uptake, and noninvasive monitoring of disease recurrence. Eventually, such agents may play a leading role in reducing the human burden of cardiovascular disease, by providing early diagnosis, noninvasive monitoring and effective therapy with reduced side effects