Electrosprayed nanoparticle delivery system for controlled release

This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 109 nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure

The effect of solvent and pressure on polycaprolactone solutions for particle and fibre formation

Polycaprolactone (PCL) is a widely used material in many applications to tackle health problems worldwide. Formed micro- or nanosized PCL particles and fibres benefit from a higher surface area to volume ratio and are valuable in those applications, thus there is always a push to achieve smaller diameters. Electrohydrodynamic (EHD) technologies have been at the forefront in the production of polymeric biomaterials, and pressurised gyration (PG) has also enhanced possibilities by its ability to spin comparable fibres at rapid speeds. In this work, PCL microparticles and fibres were separately produced by changing key operating parameters of EHD and PG systems and PCL solution properties. Initially, PCL microparticles were formed by electrospraying with different binary solvent systems, followed by pressurised gyration fibre production with various singular solvents and a pre-optimised binary solvent system. As anticipated, the use of binary systems altered particle morphologies and diameters, while increased pressure and the use of different solvents greatly affected the characteristics of resulting fibres. The morphology of PCL was found to be highly dependent on the solvents and operating parameters of the technology used

Bi2Te1.6S1.4 - a Topological Insulator in the Tetradymite Family

We describe the crystal growth, crystal structure, and basic electrical properties of Bi2Te1.6S1.4, which incorporates both S and Te in its Tetradymite quintuple layers in the motif -[Te0.8S0.2]-Bi-S-Bi-[Te0.8S0.2]-. This material differs from other Tetradymites studied as topological insulators due to the increased ionic character that arises from its significant S content. Bi2Te1.6S1.4 forms high quality crystals from the melt and is the S-rich limit of the ternary Bi-Te-S {\gamma}-Tetradymite phase at the melting point. The native material is n-type with a low resistivity; Sb substitution, with adjustment of the Te to S ratio, results in a crossover to p-type and resistive behavior at low temperatures. Angle resolved photoemission study shows that topological surface states are present, with the Dirac point more exposed than it is in Bi2Te3 and similar to that seen in Bi2Te2Se. Single crystal structure determination indicates that the S in the outer chalcogen layers is closer to the Bi than the Te, and therefore that the layers supporting the surface states are corrugated on the atomic scale.Comment: To be published in Physical Review B Rapid Communications 16 douuble spaced pages. 4 figures 1 tabl

IL-27R signalling mediates early viral containment and impacts innate and adaptive immunity after chronic lymphocytic choriomeningitis virus infection

Chronic viral infections represent a major challenge to host's immune response and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin 27 (IL-27), in the control of chronic infection. We found that IL-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells. In particular, plasmacytoid DCs (pDCs), the most potent type-1-interferon (IFN-I) producing cells, significantly increased il27p28 in a TLR7 dependent fashion. Notably, mice deficient in IL-27 specific receptor (R), WSX-1, exhibited a pleiotropy of innate and adaptive immune alterations after chronic LCMV infection, including compromised NK cell cytotoxicity and antibody responses. While, the majority of these immune alterations appeared cell-extrinsic, cell-intrinsic IL-27R was necessary to maintain early pDC numbers, which, alongside lower IFN-I transcription in CD11b+ DCs and myeloid cells, may explain the compromised IFN-I elevation that we observed early after LCMV Cl13 infection in IL-27R-deficient mice. Together these data highlight the critical role of IL-27 in enabling optimal anti-viral immunity early and late after infection with a systemic persistent virus and suggest that a previously unrecognized positive feedback-loop mediated by IL-27 in pDCs might be involved in this process

Foregrounds for observations of the cosmological 21 cm line: II. Westerbork observations of the fields around 3C196 and the North Celestial Pole

In the coming years a new insight into galaxy formation and the thermal history of the Universe is expected to come from the detection of the highly redshifted cosmological 21 cm line. The cosmological 21 cm line signal is buried under Galactic and extragalactic foregrounds which are likely to be a few orders of magnitude brighter. Strategies and techniques for effective subtraction of these foreground sources require a detailed knowledge of their structure in both intensity and polarization on the relevant angular scales of 1-30 arcmin. We present results from observations conducted with the Westerbork telescope in the 140-160 MHz range with 2 arcmin resolution in two fields located at intermediate Galactic latitude, centred around the bright quasar 3C196 and the North Celestial Pole. They were observed with the purpose of characterizing the foreground properties in sky areas where actual observations of the cosmological 21 cm line could be carried out. The polarization data were analysed through the rotation measure synthesis technique. We have computed total intensity and polarization angular power spectra. Total intensity maps were carefully calibrated, reaching a high dynamic range, 150000:1 in the case of the 3C196 field. [abridged]Comment: 20 pages, 22 figures, accepted for publication in A&A. A version with full resolution figures is available at http://www.astro.rug.nl/~bernardi/NCP_3C196/bernardi.pd

Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.

Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy.C.E.R. was supported by Wellcome Trust 092627/Z/10/Z, J.A.H. by an Irvington Institute Postdoctoral Fellowship from the Cancer Research Institute (New York), and E.I.Z. by a Leukemia and Lymphoma Society Scholar Award and a grant from the NIH AI081923. We thank Dr. Graham Lord (King’s College London) for the kind gift of the Ifng CNS-12 promoter.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.immuni.2016.01.01

Beta-delayed-neutron studies of 135,136^{135,136}Sb and 140^{140}I performed with trapped ions

Beta-delayed-neutron ($\beta$n) spectroscopy was performed using the Beta-decay Paul Trap and an array of radiation detectors. The $\beta$n branching ratios and energy spectra for $^{135,136}$Sb and $^{140}$I were obtained by measuring the time of flight of recoil ions emerging from the trapped ion cloud. These nuclei are located at the edge of an isotopic region identified as having $\beta$n branching ratios that impact the r-process abundance pattern around the A~130 peak. For $^{135,136}$Sb and $^{140}$I, $\beta$n branching ratios of 14.6(11)%, 17.6(28)%, and 7.6(28)% were determined, respectively. The $\beta$n energy spectra obtained for $^{135}$Sb and $^{140}$I are compared with results from direct neutron measurements, and the $\beta$n energy spectrum for $^{136}$Sb has been measured for the first time