Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses.

Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-γ secretion in HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity toward target cancer cells expressing the antigen. Immunization with a MAGE-A3 epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in specific IFN-γ secretion and cell lysis by 6-fold and 9-fold, respectively. Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2 nanoparticles yielded an additive effect that increased lytic activity towards cells bearing NY-ESO-1+ and MAGE-A3+. Our investigations demonstrate that formulation of CT antigens within a nanoparticle can significantly enhance antigen-specific cell-mediated responses, and the combination of the two antigens in a vaccine can preserve the increased individual responses that are observed for each antigen alone

The Mediating and Moderating Effects of Teacher Preference on the Relations between Students’ Social Behaviors and Peer Acceptance

Tested on a sample of 1,365 Hong Kong primary school students from five grades, teacher preference or the extent to which the classroom teacher likes a child in the class was found to both mediate and, to a lesser extent, moderate the relations between children’s social behaviors and peer acceptance across age groups. The mediating effect suggests that peer acceptance responds not only to the behavior of a student but also to how much the classroom teacher likes or dislikes the student. The moderating effect suggests that the associations between student social behaviors and peer acceptance differ as functions of teacher preference. The mediating teacher preference was stronger with younger children, whereas a stronger moderating teacher preference was found for the older children. These findings confirm the supposition that three social processes involving the teacher, children, and peers contribute to children’s social status and relations in the classroom

In situ phase transformation synthesis of unique Janus Ag2O/Ag2CO3 heterojunction photocatalyst with improved photocatalytic properties

Herein, Ag2O/Ag2CO3 nanocomposite with unique Janus morphology was synthesized by a facile ion-exchange followed by an in situ phase transformation method with precise control of its nucleation and growth processes. Contrary to conventional synthetic procedures of Janus architectures, the present Janus system was constructed without the need for surfactants or toxic chemicals. Most importantly, the visible-light-absorbing Janus Ag2O/Ag2CO3 nanocomposite exhibits a remarkable performance toward the degradation of Rhodamine B and 4-chlorophenol, far superior to that observed for bare Ag2CO3. The obvious enhancement of the photocatalytic performance of this nanocomposite is mainly attributed to the intimate Ag2O/Ag2CO3 interface created by its exceptional Janus architecture, which in turn allows for rapid charge transfer processes. Additionally, the Janus system exhibited a high photostability during recycling experiments with no significant change in the degradation activity

Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1 alpha PARylation in db/db mice

Objective Human TNKS, encoding tankyrase 1 (TNKS1), localizes to a susceptibility locus for obesity and type 2 diabetes mellitus (T2DM). Here, we addressed the therapeutic potential of G007-LK, a TNKS-specific inhibitor, for obesity and T2DM. Methods We administered G007-LK to diabetic db/db mice and measured the impact on body weight, abdominal adiposity, and serum metabolites. Muscle, liver, and white adipose tissues were analyzed by quantitative RT-PCR and western blotting to determine TNKS inhibition, lipolysis, beiging, adiponectin level, mitochondrial oxidative metabolism and mass, and gluconeogenesis. Protein interaction and PARylation analyses were carried out by immunoprecipitation, pull-down and in situ proximity ligation assays. Results TNKS inhibition reduced body weight gain, abdominal fat content, serum cholesterol levels, steatosis, and proteins associated with lipolysis in diabetic db/db mice. We discovered that TNKS associates with PGC-1 alpha and that TNKS inhibition attenuates PARylation of PGC-1 alpha, contributing to increased PGC-1 alpha level in WAT and muscle in db/db mice. PGC-1 alpha upregulation apparently modulated transcriptional reprogramming to increase mitochondrial mass and fatty acid oxidative metabolism in muscle, beiging of WAT, and raised circulating adiponectin level in db/db mice. This was in sharp contrast to the liver, where TNKS inhibition in db/db mice had no effect on PGC-1 alpha expression, lipid metabolism, or gluconeogenesis. Conclusion Our study unravels a novel molecular mechanism whereby pharmacological inhibition of TNKS in obesity and diabetes enhances oxidative metabolism and ameliorates lipid disorder. This happens via tissue-specific PGC-1 alpha-driven transcriptional reprogramming in muscle and WAT, without affecting liver. This highlights inhibition of TNKS as a potential pharmacotherapy for obesity and T2DM.Peer reviewe

The LEGUE Input Catalogue for Dark Night Observing in the LAMOST Pilot Survey

We outline the design of the dark nights portion of the LAMOST Pilot Survey, which began observations in October 2011. In particular, we focus on Milky Way stellar candidates that are targeted for the LEGUE (LAMOST Experiment for Galactic Understanding and Exploration) survey. We discuss the regions of sky in which spectroscopic candidates were selected, and the motivations for selecting each of these sky areas. Some limitations due to the unique design of the telescope are discussed, including the requirement that a bright (V < 8) star be placed at the center of each plate for wavefront sensing and active optics corrections. The target selection categories and scientific goals motivating them are briefly discussed, followed by a detailed overview of how these selection functions were realized. We illustrate the difference between the overall input catalog - Sloan Digital Sky Survey (SDSS) photometry - and the final targets selected for LAMOST observation.Comment: 11 pages, 7 figures, accepted for publication in RA

Synchrotron-radiation-stimulated etching of polydimethylsiloxane using XeF2 as a reaction gas

Synchrotron-radiation-stimulated etching of silicon elastomer polydimethylsiloxane using XeF2 as an etching gas is demonstrated

Spin Relaxation in Single Layer Graphene with Tunable Mobility

Graphene is an attractive material for spintronics due to theoretical predictions of long spin lifetimes arising from low spin-orbit and hyperfine couplings. In experiments, however, spin lifetimes in single layer graphene (SLG) measured via Hanle effects are much shorter than expected theoretically. Thus, the origin of spin relaxation in SLG is a major issue for graphene spintronics. Despite extensive theoretical and experimental work addressing this question, there is still little clarity on the microscopic origin of spin relaxation. By using organic ligand-bound nanoparticles as charge reservoirs to tune mobility between 2700 and 12000 cm2/Vs, we successfully isolate the effect of charged impurity scattering on spin relaxation in SLG. Our results demonstrate that while charged impurities can greatly affect mobility, the spin lifetimes are not affected by charged impurity scattering.Comment: 13 pages, 5 figure

The biomechanical role of periodontal ligament in bonded and replanted vertically fractured teeth under cyclic biting forces

After teeth are replanted, there are two possible healing responses: periodontal ligament healing or ankylosis with subsequent replacement resorption. The purpose of this study was to compare the fatigue resistance of vertically fractured teeth after bonding the fragments under conditions simulating both healing modes. Thirty-two human premolars were vertically fractured and the fragments were bonded together with Super-Bond C&B. They were then randomly distributed into four groups (BP, CP, CA, BA). The BP and CP groups were used to investigate the periodontal ligament healing mode whilst the BA and CA groups simulated ankylosis. All teeth had root canal treatment performed. Metal crowns were constructed for the CP and CA groups. The BP and BA groups only had composite resin restorations in the access cavities. All specimens were subjected to a 260 N load at 4 Hz until failure of the bond or until 2×106 cycles had been reached if no fracture occurred. Cracks were detected by stereomicroscope imaging and also assessed via dye penetration tests. Finally, interfaces of the resin luting agent were examined by scanning electron microscope. The results confirmed that the fatigue resistance was higher in the groups with simulated periodontal ligament healing. Periodontal reattachment showed important biomechanical role in bonded and replanted vertically fractured teeth

An Algorithm for Preferential Selection of Spectroscopic Targets in LEGUE

We describe a general target selection algorithm that is applicable to any survey in which the number of available candidates is much larger than the number of objects to be observed. This routine aims to achieve a balance between a smoothly-varying, well-understood selection function and the desire to preferentially select certain types of targets. Some target-selection examples are shown that illustrate different possibilities of emphasis functions. Although it is generally applicable, the algorithm was developed specifically for the LAMOST Experiment for Galactic Understanding and Exploration (LEGUE) survey that will be carried out using the Chinese Guo Shou Jing Telescope. In particular, this algorithm was designed for the portion of LEGUE targeting the Galactic halo, in which we attempt to balance a variety of science goals that require stars at fainter magnitudes than can be completely sampled by LAMOST. This algorithm has been implemented for the halo portion of the LAMOST pilot survey, which began in October 2011.Comment: 17 pages, 7 figures, accepted for publication in RA