Tailored design of NKT-stimulatory glycolipids for polarization of immune responses.

Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids. Many analogues have been generated by modification of the galactosyl moiety, the acyl chain or the phytosphingosine chain of α-GalCer. Some of the analogues showed greater abilities than α-GalCer in polarizing immune responses toward Th1 or Th2 dominance. Among them, several analogues containing phenyl groups in the lipid tails were more potent in inducing Th1-skewed cytokines and exhibited greater anticancer efficacy than α-GalCer. Analyses of the correlation between structure and activity of various α-GalCer analogues on the activation of iNKT cell revealed that CD1d-glycolipid complexes interacted with the same population of iNKT cell expressing similar T-cell receptor Vβ as α-GalCer. On the other hand, those phenyl glycolipids with propensity for Th1 dominant responses showed greater binding avidity and stability than α-GalCer for iNKT T-cell receptor when complexed with CD1d. Thus, it is the avidity and stability of the ternary complexes of CD1d-glycolipid-iNKT TCR that dictate the polarity and potency of immune responses. These findings provide a key to the rationale design of immune modulating glycolipids with desirable Th1/Th2 polarity for clinical application. In addition, elucidation of α-GalCer-induced anergy, liver damage and accumulation of myeloid derived suppressor cells has offered explanation for its lacklustre anti-cancer activities in clinical trials. On other hand, the lack of such drawbacks in glycolipid analogues containing phenyl groups in the lipid tails of α-GalCer coupled with the greater binding avidity and stability of CD1d-glycolipid complex for iNKT T-cell receptor, account for their superior anti-cancer efficacy in tumor bearing mice. Further clinical development of these phenyl glycolipids is warranted

Characterizations of alphaalpha-well-posedness for parametric quasivariational inequalities defined by bifunctions

The purpose of this paper is to investigate the well-posedness issue of parametric quasivariational inequalities defined by bifunctions. We generalize the concept of $alpha$-well-posedness to parametric quasivariational inequalities having a unique solution and derive some characterizations of $alpha$-well-posedness. The corresponding concepts of $alpha$-well-posedness in the generalized sense are also introduced and investigated for the problems having more than one solution. Finally, we give some sufficient conditions for $alpha$-well-posedness of parametric quasivariational inequalities

Hybrid PolyLingual Object Model: An Efficient and Seamless Integration of Java and Native Components on the Dalvik Virtual Machine

Copyright © 2014 Yukun Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. JNI in the Android platform is often observed with low efficiency and high coding complexity. Although many researchers have investigated the JNI mechanism, few of them solve the efficiency and the complexity problems of JNI in the Android platform simultaneously. In this paper, a hybrid polylingual object (HPO) model is proposed to allow a CAR object being accessed as a Java object and as vice in the Dalvik virtual machine. It is an acceptable substitute for JNI to reuse the CAR-compliant components in Android applications in a seamless and efficient way. The metadata injection mechanism is designed to support the automatic mapping and reflection between CAR objects and Java objects. A prototype virtual machine, called HPO-Dalvik, is implemented by extending the Dalvik virtual machine to support the HPO model. Lifespan management, garbage collection, and data type transformation of HPO objects are also handled in the HPO-Dalvik virtual machine automatically. The experimental result shows that the HPO model outweighs the standard JNI in lower overhead on native side, better executing performance with no JNI bridging code being demanded. 1

Scale response of summer urban heat island to building plot ratio and its warning parameter

Omjer građevne čestice je značajan pokazatelj arhitektonskog rasporeda koji utječe na urbani toplinski otok (UHI - urban heat island). Prethodna su istraživanja usredotočena na omjer visina/težina, gustoću zgrada i ostale pokazatelje povezane s omjerom građevne čestice, ali ne uspijevaju uspješno opisati odnos vrijeme-prostor između omjera građevne čestice i UHI te točno voditi planiranje i projekt kako bi se smanjila učinkovitost UHI-a. Metoda stupnja osjetljivosti predložena je za analiziranje reakcije vrijeme-prostor UHI-a na omjer građevne čestice u svrhu reguliranja intenziteta UHI (UHII) do kojeg je došlo prihvatljivim omjerom građevne čestice tijekom planiranja i projektiranja. Osjetljivost omjera građevnih čestica u različitim prostornim omjerima prema UHI tijekom dana izračunata je redom pomoću 3S tehnologije, MATLABa, SPSS-a i drugih platformi zasnovanih na teoriji razmjere ekologije pejzaža i metodi geo-statističke analize. Razmatrana je krivulja promjene reakcije omjera građevne čestice na UHI u najosjetljivijoj prostornoj ljestvici. Tada je izrađen standard prevencije i kontrole UHI-a ljeti prema temperaturi tijekom najtoplijih ljetnih dana i ljudskoj fiziološkoj reakciji kod visokih temperatura, i odgovarajućim nacionalnim pravilima. Dano je upozorenje na parametre omjera građevne čestice na temelju porasta temperature UHI-a zbog omjera građevne čestice. Rezultati pokazuju da postoji skala osjetljivosti između omjera građevne čestice i UHI. Po danu se odnos između osnovnog omjera građevne čestice i ljetnog UHI-a pomiče od negativne ka pozitivnoj korelaciji. Učinak porasta temperature poslije podne veći je od jutarnjeg rashlađenja. Osnovni omjer građevne čestice je u linearnom odnosu s ljetnim UHII. Povećanje prosječnog omjera čestice dovodi do smanjenja UHI za 0,76 °C ujutro i porasta za 0,97 °C poslije podne. Optimalni radijus osjetljivosti omjera građevne čestice na ljetni UHI iznosi 230 m. Mehanizam reakcije omjera građevne čestice na UHI nastaje uglavnom zbog obujma pohranjene topline i zaustavljanja topline zračenja. Zaključak ove analize može pružiti podršku znanstveno teoretskom parametru u arhitektonskom dizajnu i urbanom planiranju i dizajnu.Plot ratio is an important indicator of architectural layout that affects urban heat island (UHI). Previous studies focus on street height/weight ratio, building density, and other indicators related to plot ratio but fail to effectively describe the time-space relationship between plot ratio and UHI and accurately guide the planning and design to reduce the UHI in the effective scale. The scale sensitivity method was proposed to study the time-space response of UHI to plot ratio to control the UHI intensity (UHII) caused by plot ratio during planning and design in a reasonable scale. The sensitivity of plot ratios in different space scales to UHI in the daytime was repeatedly calculated on 3S technology, MATLAB, SPSS, and other data analysis platforms based on the scale theory of landscape ecology and the method of geo-statistics analysis. The change curve of the response of plot ratio on UHI in the most sensitive space scale was discussed. The prevention and control standard of summer UHI was then constructed in accordance with the temperature in dog days of summer, human physiological reaction under high temperature, and relevant national regulations. The warning control was taken on the parameters of plot ratio on the basis of the temperature rise of UHI caused by plot ratio. Results show that scale sensitivity exists between plot ratio and UHI. In the daytime, the relationship between core plot ratio and summer UHI shifts from negative correlation to positive correlation. The temperature-rising effect in the afternoon is greater than the cooling effect in the morning. Core plot ratio has a linear relationship with summer UHII. The increase in the average core plot ratio reduces the UHII by 0,76 °C in the morning and increases it by 0,97 °C in the afternoon. The optimal sensitive radius of the core plot ratio on summer UHI is 230 m. The response mechanism of plot ratio on UHI is mainly due to heat storage volume and block to radiation heat. The study conclusion can provide scientific theoretical parameter support for architectural design and urban planning and design

Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n−6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n−6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n−6 AA and increased D6D activity can lead to enhanced n−6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention

Single Walled Carbon Nanotubes Exhibit Dual-Phase Regulation to Exposed Arabidopsis Mesophyll Cells

Herein we are the first to report that single-walled carbon nanotubes (SWCNTs) exhibit dual-phase regulation to Arabidopsis mesophyll cells exposed to different concentration of SWCNTs. The mesophyll protoplasts were prepared by enzyme digestion, and incubated with 15, 25, 50, 100 μg/ml SWCNTs for 48 h, and then were observed by optical microscopy and transmission electron microscopy, the reactive oxygen species (ROS) generation was measured. Partial protoplasts were stained with propidium iodide and 4'-6- diamidino-2-phenylindole, partial protoplasts were incubated with fluorescein isothiocyanate-labeled SWCNTs, and observed by fluorescence microscopy. Results showed that SWCNTs could traverse both the plant cell wall and cell membrane, with less than or equal to 50 μg/ml in the culture medium, SWCNTs stimulated plant cells to grow out trichome clusters on their surface, with more than 50 μg/ml SWCNTs in the culture medium, SWCNTs exhibited obvious toxic effects to the protoplasts such as increasing generation of ROS, inducing changes of protoplast morphology, changing green leaves into yellow, and inducing protoplast cells' necrosis and apoptosis. In conclusion, single walled carbon nanotubes can get through Arabidopsis mesophyll cell wall and membrane, and exhibit dose-dependent dual-phase regulation to Arabidopsis mesophyll protoplasts such as low dose stimulating cell growth, and high dose inducing cells' ROS generation, necrosis or apoptosis