Cytotoxic T-lymphocyte Antigen-4 Binding to SHP2 Interacting Transmembrane Adapter Protein by Phosphorylation in T-Cell

Purpose: To investigate potential cytotoxic T-lymphocyte antigen-4 (CTLA-4) binding partners and assess whether potential binding partners affect the full function of CTLA-4. .Methods: The down-regulation effects of CTLA-4 and SIT were assessed by culturing CD3 stimulated T-cells. CTLA-4 and SIT proteins were measured by immunoblot analysis and production of interlukin-2 transcription activity evaluated by luciferase assay.Results: CTLA-4 inhibited the interlukin-2 production capacity of CD3-stimulated T cells. CTLA-4 interaction with SHP2 interacting transmembrane adapter protein (SIT) in the down-regulation of the transcription of Interulin-2 required CTLA-4 binding to SIT tyrosine motifs. The SIT tyrosine mutants were significantly lower (25 – 75 %) after phosphorylation compared with WT-SIT (transfected cells, p < 0.05) and untreated control. The remaining 90 % phosphorylation in the F188ANS mutant can be explained by phosphorylation of other tyrosines in the sequence of SIT (p < 0.05). For interukin-2 transcription, F188ANS single mutant and double F148SEV mutant, increased NF-AT activity by 35 % compared with the wild type (p < 0.05).Conclusion: The findings imply that SIT transmembrane adaptor (SIT) protein, binds to CTLA-4 and thus potentiates the inhibitory role of this co-receptor. This phenomenon may lead to the development of new treatment strategies for autoimmune diseases and graft rejection.Keywords: Cytotoxic T-lymphocyte antigen-4, Interleukin-2, Nuclear factor of activated T-cells/Activator protein-1, SHP2 interacting transmembrane adapter protein, Autoimmune diseases, Graft rejectio

Particulate counter electrode system for enhanced light harvesting in dye-sensitized solar cells

A particulate counter electrode with photo scattering and redox catalytic properties is applied to dye sensitized solar cells (DSSCs) in order to improve photo conversion efficiency and simplify the assembly process. Our particulate counter electrode acts as both a photo reflecting layer and a catalyst for reduction of electrolyte. The reflective and catalytic properties of the electrode are investigated through optical and electrochemical analysis, respectively. A short circuit current density enhancement is observed in the DSSCs without the need to add an additional reflecting layer to the electrode. This leads to a simplified assembly process. (C) 2013 Optical Society of Americ

Electrochemical Investigation of High-Performance Dye-Sensitized Solar Cells Based on Molybdenum for Preparation of Counter Electrode

In order to improve the photocurrent conversion efficiency of dye-sensitized solar cells (DSSCs), we studied an alternative conductor for the counter electrode and focused on molybdenum (Mo) instead of conventional fluorine-doped tin oxide (FTO). Because Mo has a similar work function to FTO for band alignment, better formability of platinum (Pt), and a low electric resistance, using a counter electrode made of Mo instead of FTO lead to the enhancement of the catalytic reaction of the redox couple, reduce the interior resistance of the DSSCs, and prevent energy-barrier formation. Using electrical measurements under a 1-sun condition (100 mW/cm(2), AM 1.5), we determined that the fill factor (FF) and photocurrent conversion efficiency (eta) of DSSCs with a Mo electrode were respectively improved by 7.75% and 5.59% with respect to those of DSSCs with an FTO electrode. Moreover, we have investigated the origin of the improved performance through surface morphology analyses such as scanning electron microscopy and electrochemical analyses including cyclic voltammetry and impedance spectroscopy

Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

AbstractBackgroundThe aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy.Materials and methodsWe analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration.ResultsAfter bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy.ConclusionsIn summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy

An Efficient Noninvasive Neuromodulation Modality for Overactive Bladder Using Time Interfering Current Method

Objective: The present study aimed to evaluate a new tibial nerve stimulation (TNS) modality, which uses interferential currents, in terms of the stimulation electric field penetration efficiency into the body and physiological effectiveness. Methods: In silico experiments were performed to analyze the penetration efficiency of proposed interferential current therapy (ICT). Based on this, we performed in vivo experiments to measure excitation threshold of ICT for the tibial nerve, which is related to stimulation field near the nerve. Regarding analysis of the physiological effectiveness, in vivo ICT-TNS was performed, and changes in bladder contraction frequency and voiding volume were measured. The penetration efficiency and physiological effectiveness of ICT were evaluated by comparison with those of conventional TNS using transcutaneous electrical nerve stimulation (TENS). Results: Simulation results showed that ICT has high penetration efficiency, thereby generating stronger field than TENS. These results are consistent with the in vivo results that nerve excitation threshold of ICT is lower than that of TENS. Moreover, ICT-TNS decreased contraction frequency and increased voiding volume, and its performance was profound compared with that of TENS-TNS. Conclusion: The proposed ICT is more efficient in inducing the stimulation field near the tibial nerve placed deep inside the body compared with conventional TENS and shows a good clinical effectiveness for TNS. Significance: The high efficiency of ICT increases the safety of noninvasive neurostimulation; therefore, it has clinical potential to become a promising modality for TNS to treat OAB and other peripheral neurostimulations.11Nsciescopu

Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT

BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed. MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method. RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001). CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell

Effect of Adenotonsillectomy on Attention in Korean Children With Sleep-Disordered Breathing

Objectives Pediatric sleep-disordered breathing (SDB) is a common debilitating disorder that can adversely affect the attention and academic performance of school-age children. Unfortunately, only a few studies have examined the effect of SDB treatment on attention in pediatric populations. Therefore, the aim of this study was to prospectively investigate the effect of SDB treatment on attention in children. Methods This study consecutively enrolled SDB children with adenotonsillar hypertrophy. All subjects underwent standard-of-care treatment (adenotonsillectomy or close observation) and were evaluated using a computerized comprehensive attention test at the initial visit. Comprehensive attention tests consisted of both sustained and divided attention tasks. Each completed task was assigned an attention score, which was based on the number of omission or commission errors. The comprehension attention test was repeated 1 year later. Results A total of 171 children who underwent adenotonsillectomy and 32 children who did not undergo adenotonsillectomy were included in this study. At baseline, there was no significant difference according to the score of all type comprehension attention tests between children in the adenotonsillectomy group and in the observation group. One year after treatment, children in the adenotonsillectomy group had significantly improved scores in all attention tasks. Children in the observation group had only significant improvement in omission errors on sustained attention tasks. Meanwhile, the attention score based on commission errors of divided attention tasks was significantly worse than at baseline for those. Conclusion Our study showed that adenotonsillectomy may be helpful in improving attention in children with SDB

Nanopores of carbon nanotubes as practical hydrogen storage media

We report on hydrogen desorption mechanisms in the nanopores of multiwalled carbon nanotubes (MWCNTs). The as-grown MWCNTs show continuous walls that do not provide sites for hydrogen storage under ambient conditions. However, after treating the nanotubes with oxygen plasma to create nanopores in the MWCNTs, we observed the appearance of a new hydrogen desorption peak in the 300–350 K range. Furthermore, the calculations of density functional theory and molecular dynamics simulations confirmed that this peak could be attributed to the hydrogen that is physically adsorbed inside nanopores whose diameter is approximately 1 nm. Thus, we demonstrated that 1 nm nanopores in MWCNTs offer a promising route to hydrogen storage media for onboard practical applications