Temperature dependence of positron trapping at voids in metals

We report positron-lifetime measurements in void-containing aluminum samples, which show strong temperature dependence for the positron trapping probability. A theory is presented for the positron motion and trapping in a three-dimensional array of large voids, which compares favorably with the experimental data. It is shown that at low temperatures the trapping is transition limited and strongly temperature dependent with a crossover to diffusion-limited and weakly-temperature-dependent behavior at high temperatures.Peer reviewe

Student participatory role profiles in collaborative science learning: Relation of within-group configurations of role profiles and achievement

During collaborative learning, students tend to spontaneously enact different participatory roles that may significantly affect collaborative learning processes. Only few empirical studies to date have investigated groups as systems based on emerging roles and role profiles of the participating students, and how emerging role profile configurations affect achievement. This exploration of students' self-adopted roles investigated the relationship between role profile configurations and achievement. The statistically driven identification of role profiles was based on fine-grained observations of student groups' interactions in two distinct collaborative science-learning settings. While higher achieving groups typically exhibited versatile science-oriented role profile configurations, opinion-based configurations prevailed in lower achieving groups. Although role profiles with a social orientation were rare, a student with a distracting profile can have a significant influence on group work. Consolidated by in-depth case examples, the findings highlight the importance of understanding how collaborating groups' emergent role profiles dynamically interact during collaborative learning and how different role profile configurations relate to achievement

KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies

Author summaryKaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). The main proliferative component of KS, spindle cells, express markers of lymphatic and blood endothelium. Endothelial precursor cells, which are circulating endothelial colony forming cells (ECFCs), have been proposed as the source of spindle cells. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are readily infected by KSHV, maintain the viral episomes and show modest transformation of the cells, which the infected blood ECFCs and all uninfected ECFCs failed to show. The lymphatic ECFCs express SOX18, which supported the maintenance of high copy numbers of KSHV genomes. The KSHV-infected lymphatic ECFCs persisted in vivo and recapitulated the phenotype of KS tumor cells such as high number of viral genome copies and spindling morphology. These KS tumor cell hallmarks were significantly reduced by SOX18 chemical inhibition using a small molecule SM4 treatment. These data suggest that KSHV-infected lymphatic ECFCs could be the progenitors of KS spindle cells and are a promising model for the translational studies to develop new therapies for KS.Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells. We previously identified two types of circulating endothelial colony forming cells (ECFCs), ones that expressed markers of blood endothelium and ones that expressed markers of lymphatic endothelium. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are significantly more susceptible to KSHV infection than the blood ECFCs and maintain the viral episomes during passage in culture while the blood ECFCs lose the viral episome. Only the KSHV-infected lymphatic ECFCs (K-ECFCLY) grew to small multicellular colonies in soft agar whereas the infected blood ECFCs and all uninfected ECFCs failed to proliferate. The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. These data suggest that KSHV-infected lymphatic ECFCs can be utilized as a KSHV infection model for in vivo translational studies to test novel inhibitors representing potential treatment modalities for KS.Peer reviewe

Non-axisymmetric accretion on the classical TTS RW Aur A

(Abridged) High-resolution spectroscopic monitoring of RW Aur A was carried out in 1996, 1998 and 1999 with simultaneous B, V photometry. A multicomponent spectrum is revealed with a veiled photospheric spectrum, broad emissions, narrow emission lines of helium, and accretion, wind and shell features. Periodic modulations in many spectral features were found. The photospheric absorption lines show sinusoidal variations in radial velocity with an amplitude of +-6 km/s and a period of about 2.77 days. The radial velocities of the narrow emission lines of He vary with the same period but in anti-phase to the photospheric lines. The equivalent widths of the narrow emissions vary with a phase-shift with respect to the velocity curve. The strength of the red-shifted accretion components of Na D and other lines is also modulated with the same period. The broad emission lines of metals vary mostly with the double period of about 5.5 days. One unexpected result is that no correlation was found between the veiling and the brightness, although both varied in wide ranges. This is partly due to a contribution of the shell absorption to the photospheric line profiles, which make them vary in width and depth thus simulating lower veiling. Most of the observed features can be interpreted in the framework of non-axisymmetric magnetospheric accretion. We consider two possible models. In the first the asymmetry is induced by orbital motion of an invisible, low mass secondary, which also influences the gasflows around the star, the second considers rotational modulation of a single star with an inclined or asymmetric magnetosphere

Polarization conversion by dielectric subwavelength gratings in conical mounting

Subwavelength dielectric gratings are examined in total-internal-reflection configuration. It is demonstrated experimentally that such elements, fabricated in TiO2, can perform full polarization conversion from incident TE to TM with nearly 100% efficiency. The dependence of the polarization conversion on the angle of incidence is analyzed. Rigorous diffraction theory is used to cross check the experimental results

Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

Magnetic resonance imaging examinations are frequently carried out using contrast agents to improve the image quality. Practically all clinically used contrast agents are based on paramagnetic metals and lack in selectivity and specificity. A group of stable organic radicals, nitroxides, has raised interest as new metal-free contrast agents for MRI. Their structures can easily be modified to incorporate different functionalities. In the present study, a stable nitroxide TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl) was linked to a glucose moiety (Glc) to construct a water-soluble, potentially tumor-targeting compound with contrast-enhancing ability. The ability was assessed with in vivo MRI experiments. The constructed TEEPO-Glc agent proved to shorten the T-1 relaxation time in tumor, while the T-1 time in healthy brain tissue remained the same. The results indicate the potential of TEEPO-Glc as a valuable addition to the growing field of metal-free contrast enhancement in MRI-based diagnostics.Peer reviewe

Heparin-Derived Theranostic Nanoprobes Overcome the Blood-Brain Barrier and Target Glioma in Murine Model

The poor permeability of theranostic agents across the blood-brain barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. A new biomimetic nanocarrier is discovered using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, HP-coated gold nanoparticles (HP-AuNPs) are designed that are labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope (68)Gallium (Ga-68-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displays excellent penetration and reveals uniform distribution of fluorescent particles in the brain parenchyma (69-86%) with some accumulation in neurons (8-18%) and microglia (4-10%). Tail-vein administration of radiolabeled Ga-68-HP-AuNPs in healthy rats also show Ga-68-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that displays approximate to threefold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrates enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1 and 3 h. It is believed, the finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.Peer reviewe

Monotherapy efficacy of blood-brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma

Glioblastoma is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumour suppressors has not been thoroughly studied as yet as a glioblastoma therapeutic strategy. Tumour suppressor protein phosphatase 2A is inhibited by non-genetic mechanisms in glioblastoma, and thus, it would be potentially amendable for therapeutic reactivation. Here, we demonstrate that small molecule activators of protein phosphatase 2A, NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood-brain barrier, and in vivo partition to mouse brain tissue after oral dosing. In vitro, small molecule activators of protein phosphatase 2A exhibit robust cell-killing activity against five established glioblastoma cell lines, and nine patient-derived primary glioma cell lines. Collectively, these cell lines have heterogeneous genetic background, kinase inhibitor resistance profile and stemness properties; and they represent different clinical glioblastoma subtypes. Moreover, small molecule activators of protein phosphatase 2A were found to be superior to a range of kinase inhibitors in their capacity to kill patient-derived primary glioma cells. Oral dosing of either of the small molecule activators of protein phosphatase 2A significantly reduced growth of infiltrative intracranial glioblastoma tumours. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested glioblastoma cell lines, also significantly increased survival of mice bearing orthotopic glioblastoma xenografts. In summary, this report presents a proof-of-principle data for blood-brain barrier-permeable tumour suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background. These results also provide the first indications that protein phosphatase 2A reactivation might be able to challenge the current paradigm in glioblastoma therapies which has been strongly focused on targeting specific genetically altered cancer drivers with highly specific inhibitors. Based on demonstrated role for protein phosphatase 2A inhibition in glioblastoma cell drug resistance, small molecule activators of protein phosphatase 2A may prove to be beneficial in future glioblastoma combination therapies.Peer reviewe