Glass-Like Phonon Dynamics and Thermal Transport in a GeTe Nano-Composite at Low Temperature.

In this work, the experimental evidence of glass-like phonon dynamics and thermal conductivity in a nanocomposite made of GeTe and amorphous carbon is reported, which is of interest for microelectronics, and specifically phase change memories. It is shown that, the total thermal conductivity is reduced by a factor of three at room temperature with respect to pure GeTe, due to the reduction of both electronic and phononic contributions. This latter, similarly to glasses, is small and weakly increasing with temperature between 100 and 300 K, indicating a mostly diffusive thermal transport and reaching a value of 0.86(7) Wm-1K-1 at room temperature. A thorough investigation of the nanocomposite's phonon dynamics reveals the appearance of an excess intensity in the low energy vibrational density of states, reminiscent of the Boson peak in glasses. These features can be understood in terms of an enhanced phonon scattering at the interfaces, due to the presence of elastic heterogeneities, at wavelengths in the 2-20 nm range. The findings confirm recent simulation results on crystalline/amorphous nanocomposites and open new perspectives in phonon and thermal engineering through the direct manipulation of elastic heterogeneities.

Role of vacancies in metal-insulator transitions of crystalline phase-change materials.

The study of metal-insulator transitions (MITs) in crystalline solids is a subject of paramount importance, both from the fundamental point of view and for its relevance to the transport properties of materials. Recently, a MIT governed by disorder was observed in crystalline phase-change materials. Here we report on calculations employing density functional theory, which identify the microscopic mechanism that localizes the wavefunctions and is driving this transition. We show that, in the insulating phase, the electronic states responsible for charge transport are localized inside regions having large vacancy concentrations. The transition to the metallic state is driven by the dissolution of these vacancy clusters and the formation of ordered vacancy layers. These results provide important insights on controlling the wavefunction localization, which should help to develop conceptually new devices based on multiple resistance states.

Measurement of the refractive index of highly turbid media: comment.

We comment on the recent Letter by Calhoun et al. [Opt. Lett. 35, 1224 (2010)]. We wish to correct their statement about the order of the magnitude of the absorption coefficient of inks that we have we studied. In addition, we consider the inconsistency of their theoretical model with the experimental data obtained for milk and milk-cream samples.

(Strept)avidin-displaying lentiviruses as versatile tools for targeting and dual imaging of gene delivery.

Lentiviruses have shown great promise for human gene therapy. However, no optimal strategies are yet available for noninvasive imaging of virus biodistribution and subsequent transduction in vivo. We have developed a dual-imaging strategy based on avidin-biotin system allowing easy exchange of the surface ligand on HIV-derived lentivirus envelope. This was achieved by displaying avidin or streptavidin fused to the transmembrane anchor of vesicular stomatitis virus G protein on gp64-pseudotyped envelopes. Avidin and streptavidin were efficiently incorporated on virus particles, which consequently showed binding to biotin in ELISA. These vectors, conjugated to biotinylated radionuclides and engineered to express a ferritin transgene, enabled for the first-time dual imaging of virus biodistribution and transduction pattern by single-photon emission computed tomography and magnetic resonance imaging after stereotactic injection into rat brain. In addition, vector retargeting to cancer cells overexpressing CD46, epidermal growth factor and transferrin receptors using biotinylated ligands and antibodies was demonstrated in vitro. In conclusion, we have generated novel lentivirus vectors for noninvasive imaging and targeting of lentivirus-mediated gene delivery. This study suggests that these novel vectors could be applicable for the treatment of central nervous system disorders and cancer.

Polarization vortices in germanium telluride nanoplatelets: a theoretical study.

Using first-principles calculations based on density functional theory, we study the properties of germanium telluride crystalline nanoplatelets and nanoparticles. Above a diameter of 2.7 nm, we predict the appearance of polarization vortices giving rise to an unusual ferrotoroidic ground state with a spontaneous and reversible toroidal moment of polarization. We highlight the crucial role of inhomogeneous strain in stabilizing polarization vortices. Combined with the phase-change properties of germanium telluride, the ferrotoroidic properties could be of practical interest for ternary logic applications.

Revealing the role of molecular rigidity on the fragility evolution of glass-forming liquids.

If quenched fast enough, a liquid is able to avoid crystallization and will remain in a metastable supercooled state down to the glass transition, with an important increase in viscosity upon further cooling. There are important differences in the way liquids relax as they approach the glass transition, rapid or slow variation in dynamic quantities under moderate temperature changes, and a simple means to quantify such variations is provided by the concept of fragility. Here, we report molecular dynamics simulations of a typical network-forming glass, Ge-Se, and find that the relaxation behaviour of the supercooled liquid is strongly correlated to the variation of rigidity with temperature and the spatial distribution of the corresponding topological constraints, which ultimately connect to the fragility minima. This permits extending the fragility concept to aspects of topology/rigidity, and to the degree of homogeneity of the atomic-scale interactions for a variety of structural glasses.

Compression forces of haptics of selected posterior chamber lenses.

PURPOSE: To compare the compressive forces of the haptics of different intraocular lens (IOL) models and analyze the observed differences. SETTING: Central Hospital of Central Finland and University of Jyväskylä, Jyväskylä, Finland. METHODS: The haptics of 28 IOL models were compressed to a diameter of 9.0 mm. The compression forces were measured at 0.5 mm intervals. The conclusions were verified by numerical simulations of mechanical models of the lenses. RESULTS: The measured forces varied between 100 and 601 mg at a diameter of 11.0 mm, 206 and 1057 mg at a diameter of 10.0 mm, and 315 and 2094 mg at a diameter of 9.0 mm. The slopes of the force curves of the three-piece lenses were fairly linear. In general, the three-piece models were less rigid than one-piece models and underwent plastic deformations after repeated compressions. For most one-piece models, compression force increased progressively with increasing compression. The overall IOL diameter and differences in haptic thickness and length and the angle between optic at the point of haptic insertion were the main causes of the observed differences in the compression forces. The variation in forces between individual specimens of the same model, which occurred with almost all models, were mainly the result of variations in haptic thickness. CONCLUSION: Great variations in the compression forces of the IOL haptics were found. Compression behaviors should be taken into account when selecting a lens to implant.

Compression forces of haptics of freely rotating posterior chamber intraocular lenses.

PURPOSE: To measure the compressive forces of the haptics of 28 intraocular lens (IOL) models for different modes of compression and compare the results of two types of measurements. SETTING: Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä, Finland. METHODS: The haptics of 28 types of IOLs were compressed to a diameter of 9.0 mm between curved anvils. The compression forces in the plane of compression (i.e., in the plane of the optics) were measured at 0.5 mm intervals. During compression, the optics and the haptics were free to rotate with respect to the anvils. The results were compared with those of earlier measurements in which the optics were held fixed during compression. Perpendicular forces were measured at 0.4 mm intervals. RESULTS: The measured forces in the plane of the optics varied between 114 and 659 mg at a diameter of 10.0 mm and 192 and 1047 mg at a diameter of 9.0 mm. When compressed to 10.0 mm in diameter, the forces were 1 to 75% lower than when lens rotation was not possible. The forces perpendicular to the optic varied between 0 and 96 mg at a 10.0 mm diameter and correlated with the forces in the plane of the optic. CONCLUSION: The compression forces of the lens haptics were generally lower when the lenses were allowed to rotate during compression. The orders of stiffness of the haptics in these two measurements were similar. The perpendicular forces were generally small and correlated significantly with the forces measured in the plane of the optic.

Determination of the refractive index of microparticles by utilizing light dispersion properties of the particle and an immersion liquid.

The knowledge of the refractive index of a particle is important in sensing and imaging applications, e.g., in biology, medicine and process industry. The refractive index of tiny solid particles such as microsize particles can be determined by the so-called liquid immersion technique. This study deals with three different types of interrogation methods to get the refractive index of a particle in a liquid matrix. These methods utilize thermo-optical properties and wavelength-dependent refractive index of the particle and the immersion liquids, as well as, the classical method using a set of in advance prepared set of immersion liquids with different refractive indices. The emphasis is on a method to get especially the wavelength-dependent refractive index of microparticles and exploiting different wavelength-dependences of immersion liquid and a solid particle because identification of a particle is more reliable if the refractive index of the particle is known at several wavelengths. In this study glycerol-water mixtures served as immersion liquids to obtain the refractive index of CaF2 at several discrete wavelengths in the spectral range 200-500 nm. The idea is to find the maximum value of light transmission of suspension by scanning the wavelength of a commercial spectrophotometer. The light dispersion-based method is suggested as a relatively easy, economic and fast method to determine the refractive index of a particle by a spectrophotometer at several wavelengths of light. The accuracy of the detection of the refractive index is suggested to be better than ± 0.005 refractive index units.

Gene therapy: the first approved gene-based medicines, molecular mechanisms and clinical indications.

As gene therapy has matured from clinical trials to the first commercial products, understanding of the mechanisms of gene delivery has increased tremendously. This has also been reflected in viral vector development, creating a number of new approaches to tackle issues in transduction efficiency, biodistribution and viral safety. This review will highlight the most important issues and advancements in vector development, administration, surface modification, integration to host genome and safety. The gene therapy products currently available or near market approval, based on p53 expression (Gendicine and Advexin), conditionally replicative adenoviruses (Oncorine) and thymidine kinase + ganciclovir therapy (Cerepro), are introduced with emphasis on the molecular mechanisms of action.

SPECT/CT imaging of baculovirus biodistribution in rat.

Non-invasive imaging provides essential information regarding the biodistribution of gene therapy vectors and it can also be used for the development of targeted vectors. In this study, we have utilized micro Single-photon emission computed tomography to visualize biodistribution of a (99m)Tc-polylys-ser-DTPA-biotin-labelled avidin-displaying baculovirus, Baavi, after intrafemoral (i.f.), intraperitoneal (i.p.), intramuscular (i.m.) and intracerebroventricular (i.c.v.) administration. The imaging results suggest that the virus can spread via the lymphatic network after different administration routes, also showing accumulation in the nasal area after systemic administration. Extensive expression in the kidneys and spleen was seen after i.p. administration, which was confirmed by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Additionally, transduction of kidneys was seen with i.m. and i.f. administrations. We conclude that baculovirus may be beneficial for the treatment of kidney diseases after i.p. administration route.

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo.

Pseudotyping of viral vectors has been widely used to enhance viral transduction efficiency. One of the most popular pseudotyping proteins has been the G-protein of the vesicular stomatitis virus, VSV-G. In the present study, we show that the 21-amino-acid ectodomain with transmembrane and cytoplasmic tail domains of VSV-G (VSV-GED) augments baculovirus-mediated gene delivery in vertebrate cells by aiding viral entry. The VSV-GED pseudotyped virus replicated efficiently in insect cells yielding high titers. Five out of six studied cell lines showed improved transduction, as measured by a number of transduced cells or transgene expression level. Nearly 15-fold increase in the transduction efficiency was detected in rat malignant glioma cells as compared to the control virus. In the rat brain, transgene expression could be detected in the walls of lateral ventricles and in subarachnoid membranes. Increased transduction efficiency was also observed in the rabbit muscle. Our results suggest that VSV-GED enhances baculoviral gene transfer by augmenting gp64-mediated endosomal release. Moreover, no cytotoxicity was associated with improved gene transfer efficiency. Thus, VSV-GED pseudotyping provides a simple means to enhance baculovirus-mediated gene transfer in vitro and in vivo.

Magnetic resonance imaging of viral particle biodistribution in vivo.

We describe here a technique for the visualization of viral vector delivery by magnetic resonance imaging (MRI) in vivo. By conjugating avidin-coated baculoviral vectors (Baavi) with biotinylated ultra-small superparamagnetic iron oxide particles (USPIO), we are able to produce vector-related MRI contrast in the choroid plexus cells of rat brain in vivo over a period of 14 days. Ten microlitres of 2.5 x 10(10) PFU/ml nuclear-targeted LacZ-encoding Baavi with bUSPIO coating was injected into rat brain ventricles and visualized by MRI at 4.7 T. As baculoviruses exhibit restricted cell-type specificity in the rat brain, altered MRI contrast was detected in the choroid plexus of the injected ventricles. No specific signal loss was detected when wild-type baculoviruses or intact biotinylated USPIO particles were injected into the lateral ventricles. Cryosectioned brains were stained for nuclear-targeted beta-galactosidase gene expression, which was found to colocalize with MRI contrast. This study provides the first proof of principle for robust and non-invasive viral vector MRI by using avidin-displaying viruses in vivo. Considering the widespread use of MRI in current medical imaging, the approach is likely to provide numerous future applications in imaging of therapeutic gene transfer.

On reflectometric measurement of a refractive index of milk.

The refractive index of milk samples was measured with a reflectometer. Fresnel's formula for intensity reflectance and the concept of critical angle were applied to measured data. Milk samples were also measured with surface plasmon resonance sensor for refractive index assessment. The experiments were carried with commercial milk that had fat volume concentrations of 0.004, 1.53, and 3.55%. We observed that simultaneously quantitative information about the refractive index and absorption of milk, as a function of fat concentration, could be obtained with both devices.

Renography in the foetal and newborn lamb.

Hippuran renography indicates kidney function as reflected in a substance handled mainly by the tubules. The working conditions of the kidneys undergo a fundamental change at birth with the cessation of placenta circulation, and these organs become responsible for waste elimination. 131I-hippuran renography was performed on foetal and newborn lambs using a gamma camera and a computer. The intervals of the maximum- and half-time renal activity were determined. These decreased by a half from mean foetal value of Tm=7 mi and T12=19 min in 1 to 1.5 days and reached the full-grown level in 2 to 5 weeks. No sudden change occurred as a result of the first breath.

Postirradiation sarcoma. Analysis of a nationwide cancer registry material.

Thirty-three cases of postirradiation sarcoma (PIS) from the files of the Finnish Cancer Registry were analyzed. The most frequent first primary tumors were cancers of the breast (seven cases) and female reproductive organs (13 cases). Five patients had a childhood cancer. The median total radiation dose at the site of the PIS was 3600 cGy (1600 cGy to 11200 cGy). The median interval from start of radiation therapy to detection of PIS was 13.2 years (3.4 to 22.8 years). The PIS was of soft tissue origin in 25 of 33 cases. The most frequent histologic types were osteosarcoma (ten cases, including four extraskeletal tumors), malignant fibrous histiocytoma (ten cases), and fibrosarcoma (six cases). The overall crude 5-year survival rate was 29% (calculated from the start of treatment for PIS), and for patients initially treated with either radical surgery or combined marginal surgery and postoperative irradiation it was 67%. The authors conclude that there is a chance for cure for radically treated patients with postirradiation sarcoma that emphasizes the importance of regular long-term follow-up of cancer patients.

The effect of fractionated irradiation on cell kinetics.

The effects of single and split-dose irradiation were compared by in vitro experiments on HeLa cells. Changes in rate of cell proliferation were detected by flow cytometry, simultaneously determining the DNA content and the bromodeoxyuridine incorporation of individual cells. Cell cultures were irradiated with either a single dose of 1-6 Gy or with a corresponding dose divided into multiple fractions given at 1-6-h intervals. A dose-dependent accumulation of cells in G2/M phase was observed. The method was sensitive enough for the detection of G2/M block even after 1 Gy. The block disappeared completely within a 24-h follow-up time at dose levels up to 3 Gy. Interestingly, no differences in cell kinetics were observed between the single and split-dose regiments. This approach proves to be valuable in evaluating novel fractionation models and the effects of radiation on the cell kinetics of human tumor cells.

Estimation of the wavelength-dependent effective refractive index of spherical plastic pigments in a liquid matrix.

Refractive-index data are important for the prediction of light scattering from spherical pigments. Reflectance from a slurry that contains plastic pigments was studied with the aid of a reflectometer. The effective refractive index of spherical plastic pigments in a slurry was determined by use of reflectance data and a phase-retrieval procedure based on the maximum-entropy method. This method provides a simple way to estimate the effective refractive index of pigments in a liquid matrix.