Mechanism Of Poly Research Articles

Fabrication and mechanism of poly(butylene succinate) urethane ionomer microcellular foams with high thermal insulation and compressive feature

To fabricate biodegradable microcellular foams with high thermal insulation and compressive feature, poly(butylene succinate) urethane ionomer (PBSUIs) were synthesized and foamed by supercritical CO2 via batch foaming method. The intrinsic viscosities, rheological and crystallization properties of PBSUI were characterized by Ubbelohde viscometer, rotational rheometer and X-ray diffraction test, respectively. The results revealed that the complex viscosity of PBSUIs vastly increased with the rise of urethane ionic groups (UIG) content, while its intrinsic viscosity and crystallinity slightly decreased due to the physical network upon UIG aggregation. The morphology, mechanical and thermal insulation properties of PBSUIs foams were evaluated. The results demonstrated that foams morphologies were sensitive to UIG content and dominated their mechanical and thermal insulation properties. PBSUI-3 (3 wt% UIG content) and PBSUI-5 (5 wt% UIG content) microcellular foams exhibited elliptical shape and stretched in the foam-mold height direction, their cells size and opening ratio are smaller than 7.0 μm and 13%, while their cell densities are higher than 4.7 × 109 cells/cm3. Meanwhile, PBSUI-3 microcellular foam achieved 1.6 MPa compressive strength and 76 mW/m·k thermal conduction. Meanwhile, the foamed, mechanical and thermal insulation properties of PBSUIs microcellular foams were proposed. The study promoted a promising solution for biodegradable thermal insulation material applications.

Exploiting poly(I:C) to induce cancer cell apoptosis

ABSTRACTTLR3 belong to the Toll-like receptors family, it is mainly expressed on immune cells where it senses pathogen-associated molecular patterns and initiates innate immune response. TLR3 agonist poly(I:C) was developed to mimic pathogens infection and boost immune system activation to promote anti-cancer therapy. Accordingly, TLR agonists were included in the National Cancer Institute list of immunotherapeutic agents with the highest potential to cure cancer. Besides well known effects on immune cells, poly(I:C) was also shown, in experimental models, to directly induce apoptosis in cancer cells expressing TLR3.This review presents the current knowledge on the mechanism of poly(I:C)-induced apoptosis in cancer cells. Experimental evidences on positive or negative regulators of TLR3-mediated apoptosis induced by poly(I:C) are reported and strategies are proposed to successfully promote this event in cancer cells.Cancer cells apoptosis is an additional arm offered by poly(I:C), besides activation of immune system, for the treatment of various type of cancer. A further dissection of TLR3 signaling would contribute to greater resolution of the critical steps that impede full exploitation of the poly(I:C)-induced apoptosis. Experimental evidences about negative regulator of poly(I:C)-induced apoptotic program should be considered in combinations with TLR3 agonists in clinical trials.

Effect of CdS nanocrystals on charge transport mechanism in poly(3-hexylthiophene)

The present manuscript demonstrates the optical and electrical characteristics of poly(3-hexylthiophene) (P3HT) and cadmium sulphide (CdS) hybrid nanocomposites. Optical results suggest that there is a formation of charge transfer complex (CTC) between host P3HT and guest CdS nanocrystals (NCs). Electrical properties of P3HT and P3HT-CdS thin films have been studied in hole only device configurations at different temperatures (290 K–150 K), and results were analysed by the space charge limited conduction mechanism. Density of traps and characteristic trap energy increase on incorporation of inorganic NCs in the polymer matrix, which might be due to the additional favourable energy states created by CdS NCs in the band gap of P3HT. These additional trap states assist charge carriers to move quicker which results in enhancement of hole mobility from 7 × 10−6 to 5.5 × 10−5 cm2/V s in nanocomposites. These results suggest that the P3HT-CdS hybrid system has desirable optical and electrical properties for its applications to photovoltaics devices.

Superior lubrication mechanism in poly(vinyl alcohol) hybrid gel as artificial cartilage

With recent progress of material technologies, the wear resistance of ultra-high molecular weight polyethylene for total joint prostheses has been improved, but under severe conditions friction and wear problems have not yet been completely solved. Therefore, the application of artificial hydrogel cartilage with similar properties to natural articular cartilage is expected to solve the friction and wear problems by improvement of lubrication mechanism with superior tribological functions. In this study, reciprocating tests of four kinds of poly(vinyl alcohol) hydrogels were carried out and the biphasic finite element analysis was conducted. As artificial cartilage specimens, four kinds of poly(vinyl alcohol) hydrogels were prepared using the repeated freeze–thawing (FT) method, the cast-drying (CD) method and the hybrid method with different layered structure as FT on CD or CD on FT. In reciprocating test of ellipsoidal poly(vinyl alcohol) hydrogel specimen against flat glass plate in saline solution, four kinds of hydrogels exhibited very different frictional levels as hybrid (CD on FT) < CD < FT < hybrid (FT on CD). It is noticed that hybrid (CD on FT) gel maintained extremely low friction and showed minimal wear. The effectiveness of biphasic lubrication was evaluated by biphasic finite element analysis. The importance of the load support by fluid phase at early stage and the surface lubricity after lowering of interstitial fluid pressure in poly(vinyl alcohol) hybrid (CD on FT) gel are discussed by comparison of experiment and finite element analysis.

Mechanism of Poly(I: C)-induced apoptosis in lung adenocarcinoma A549 cells

Objective To study the effects of Poly(I: C) on lung adenocarcinoma A549 cells viability and illuminate the mechanism of Poly(I: C)-induced apoptosis in A549 cells. Methods A549 cells were transfected with the complex of Poly(I: C) and lipofectamine 3000. The viability of A549 cells was tested by methyl thiazolyl tetrazolium (MTT) method. The apoptotic cells were tested by flow cytometry. The caspase proteins were tested by Western blotting and the expressions of interferon-β (IFN-β) and CXCL-10 were assayed by real-time PCR. After employing the pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK, the variation of Poly(I: C) proapoptosis in A549 cells was observed. RNA interfering experiments were employed to knock down melanoma differentiation related antigen 5 (MDA5) or retinoic aci-dinduced gene Ⅰ (RIG-Ⅰ), and the above indexes were tested. Results The viability of A549 cells was significantly reduced to 74.92%±6.24% after 200 ng/ml Poly(I: C) transfection compared with that before transfection (95.32%±3.05%, t=2.883, P=0.041). The apoptotic rates induced by 100, 200, 400 ng/ml Poly(I: C) were 9.97%±0.88%, 23.63%±1.41%, 32.57%±2.39%, respectively. All of them were higher than that in the control group (0.74%±0.15%), with significant differences (t=4.489, P=0.002; t=11.616, P=0.000; t=16.932, P=0.000). Besides, the death receptor pathway proteins such as TNF-related apoptosis inducing ligand (TRAIL), cleaved-caspase-8 and cleaved-caspase-3 increased obviously. MDA5/RIG-Ⅰpathway was also activated dramatically and the expressions of IFN-β, CXCL-10 were significantly up-regulated. The apoptotic rates reduced to 3.17%±0.66%, 5.35%±0.64% with pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK pretreatment, compared with the control group (15.87%±0.93%), and the differences were statistically significant (t=8.643, P=0.001; t=6.824, P=0.002). Moreover, the expressions of TRAIL, IFN-β and CXCL-10 induced by Poly(I: C) were inhibited with MDA5 or RIG-Ⅰ depletion. Conclusion Poly(I: C) can reduce the survival rate of A549 cells and promote the apoptosis mainly by activating the death-receptor pathway mediated by MDA5/RIG-Ⅰprobably, which may involve in IFN-β, CXCL-10. Key words: Lung neoplasms; Apoptosis; Poly(I: C)

Further Insight into the Mechanism of Poly(styrene-co-methyl methacrylate) Microsphere Formation.

Polymeric microspheres have been utilized in a broad range of applications ranging from chromatographic separation techniques to analysis of air flow over aerodynamic surfaces. The preparation of microspheres from many different polymer families has consequently been extensively studied using a variety of synthetic approaches. Although there are a variety of methods of synthesis for polymeric microspheres, free-radical initiated emulsion polymerization is one of the most common techniques. In this work, poly(styrene-co-methyl methacrylate) microspheres were synthesized via surfactant-free emulsion polymerization. The effect of co-monomer composition and addition time on particle size distribution, particle formation, and particle morphology were investigated. Particles were characterized using dynamic light scattering (DLS) and scanning electron microscopy (SEM) to gain further insight into particle size and size distributions. Reaction kinetics were analyzed alongside of characterization results. A particle formation mechanism for poly(styrene-co-methyl methacrylate) microspheres was proposed based on characterization results and known reaction kinetics.

Abstract B132: Importance and mechanism of poly(A) tail length-mediated translational control in different immune cells

Abstract Translational control is an essential regulatory mechanism in immune cells. Although it has been suggested that poly(A) tail length-mediated translational control plays important roles in regulating select cytokine production in memory T cells and macrophages, whether this is a transcriptome-wide regulatory principle in all immune cells remains unknown. We set out to perform RNA-seq, ribosome-footprint profiling and poly(A) tail length profiling across major types of immune cells to examine the relationship between poly(A) tail length and translational efficiency in these systems. We also plan to delineate the transcriptome-wide landscape of poly(A) tail length before and after immune activation, and investigate if the coupling of poly(A) tail length and translational efficiency plays a regulatory role in this process. Meanwhile, to understand the general mechanistic details of how poly(A) tail length affects translational efficiency in a cell context-dependent manner, we carried out RNA pull-down experiments and isolated proteins from known coupled (Xenopus oocytes) and uncoupled (rabbit reticulocyte lysates) systems. By quantitative mass spectrometry analysis, we identified key factors that are responsible for coupling translational efficiency to poly(A) tail length. Among these candidates, poly(A) binding protein (PABPC1) plays an essential role. Overexpression of PABPC1 in Xenopus oocytes renders the translation of reporter RNAs with either a short poly(A) tail or a long poly(A) tail equally well, turning a coupled system into an uncoupled system. We have also generated an effective degron-induced PABPC1-knockdown cell line and are performing analysis to see if the coupling can be established in a normally uncoupled system. Our results suggest that cells can modify the expression of PABPC1 to help determine if poly(A) tail length regulates translational efficiency. Citation Format: Kehui Xiang, David Bartel. Importance and mechanism of poly(A) tail length-mediated translational control in different immune cells [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B132.

Superb adsorption capacity and mechanism of poly(1-amino-5-chloroanthraquinone) nanofibrils for lead and trivalent chromium ions

Poly(1-amino-5-chloroanthraquinone) (PACA) nanofibrils were applied as new nano-adsorbents for heavy metal removal from aqueous solutions. Adsorption properties including adsorption capacity, selectivity, kinetics, mechanism, and isotherm of PACA nanofibrils were studied in detail. The competitive adsorption of the nanofibrils for Pb(II) and Cr(III) in binary mixture systems was investigated. The results showed that Pb(II) and Cr(III) were adsorbed preferentially over the other metal ions including Hg(II), Cr(VI), Zn(II), Cd(II), Fe(III) and Cu(II), under competitive conditions. Kinetic data indicated that the adsorption process of PACA nanofibrils for Pb(II) and Cr(III) achieved equilibrium within 2h following a pseudo-second-order rate equation and exhibiting a three-stage intraparticle diffusion mode. The adsorption mechanism of PACA nanofibrils for Pb(II) and Cr(III) was investigated by Fourier transform infrared spectra (FT-IR) and X-ray photoelectron spectroscopy (XPS) analyses. The adsorption isotherms of Pb(II) and Cr(III) fitted well with the Langmuir model, exhibiting superb adsorption capacity of 4.27 and 4.22mmol of metal per gram of adsorbent, respectively. Furthermore, adsorption–desorption experiments demonstrated that the PACA nano-adsorbents could be easily recycled without considerable changes in the adsorption capacity.

Thermally Activated And Field Dependent Hole Transport In Poly(3-hexylthiophene)

Here, we investigate the hole transport mechanism in poly(3-hexylthiophene) (P3HT). First, ohmic contact has been established at indium tin oxide (ITO)/P3HT interface by molybdenum oxide (MoOx) hole injection layer. Thickness of MoOx layer is observed to play a crucial role with ohmic contact being observed even for 1 nm layer. However, device with less than 5 nm layer are found to be extremely unstable. A device with a 5 nm layer of MoOx is found to be stable and ohmic injection at ITO/P3HT layer enabled to observe ohmic conduction at low voltages ( 3 V. At higher voltages, effect of field on charge carrier mobility is also observed. Observation of SCLC enabled us to directly evaluate the hole mobility in P3HT which is calculated to be 5.4 × 10 -5 cm 2 /Vs. Conductivity is calculated from the low voltage region and found to be 6.85 × 10 -8 S/cm. Temperature dependent mobility is used to study the charge transport behavior and it has been observed that mobility is thermally activated with an extremely low activation energy of 39 meV. Copyright © 2016 VBRI Press.

Light‐Induced Degradation Mechanism in Poly(3‐hexylthiophene)/Fullerene Blend Solar Cells

The mechanism of light‐induced degradation in organic solar cells based on regioregular poly(3‐hexylthiophene) and indene‐C60 bisadduct is studied by transient absorption (TA) and electron spin resonance (ESR) measurements. After 45 h light exposure under simulated solar illumination at 100 mW cm−2, the short‐circuit current density, open‐circuit voltage, and fill factor are all degraded by about 20%–30% relative to the initial photovoltaic parameters. For the assignment of limiting conversion processes in the degraded solar cells, exciton diffusion into a donor/acceptor interface, charge transfer at the interface, charge dissociation into free charge carriers, and charge collection to each electrode are observed before and after the light exposure by the TA measurement. As a result, it is found that the charge collection deteriorates after the light exposure because of light‐induced charge trap formation in the bulk of the active layer. The origin of charge traps is further discussed on the basis of ESR measurements and density functional theory calculation.

Photodegradation behavior and mechanism of poly(ethylene glycol-co-1,4-cyclohexanedimethanol terephthalate) (PETG) random copolymers: correlation with copolymer composition

Norrish type I and II mechanisms occurred in PETG copolymers. The inherent photostability of PETG decreased with increasing CHDM content. The higher CHDM content resulted in the higher crosslinking degree.

Molecular separation by poly (N-vinyl imidazole) gel-filled membranes

Here we demonstrate the tunable molecular selectivities and corresponding mechanisms of poly(N-vinyl imidazole) (PVI) gel-filled membranes prepared by UV initiated graft polymerization of N-vinyl imidazole from ultraporous polysulfone (PSf) substrate. The separation performance was investigated in detail by extensive filtration tests with various organic molecules in water of varying pH and also in salt or ethanol aqueous solution. The variation of membrane water permeability and solute rejection with the feed pH was attributed to the sensitive pore size and charge characteristics of the membranes upon reversible protonation of the confined PVI gel. The separation results discerned three main mechanisms, i.e. size exclusion (sieving), electrostatic repulsion (Donnan exclusion) and adsorption. The rejection of the neutral molecules and the large dye molecules was mostly ascribed to size exclusion, while that of the small charged solutes was dominated by the electrostatic interactions including repulsion for cationic ones and attraction for anionic ones (causing specific adsorption). Typically, at pH 3 the protonated membranes rejected ~90% of the small cationic Vitamin B1 (VB1) and 100% of the anionic Sunset Yellow (SY) before adsorption saturation, in contrast to less than ~20% rejection of the neutral Vitamin B2 (VB2) having similar molecule size. In the high concentration salt or ethanol solution the membranes still maintained molecular sieving capability. Most notably, the separations of solute mixtures were indeed achieved, depending on the membrane parameters, the solute characteristics as well as the filtration conditions. The PVI gel-filled membranes developed in this work are promising in some specified or environment-sensitive molecular level separations.

Enhancing Interferon Regulatory Factor 7 Mediated Antiviral Responses and Decreasing Nuclear Factor Kappa B Expression Limit HIV-1 Replication in Cervical Tissues.

Establishment of a productive HIV-1 infection in the female reproductive tract likely depends on the balance between anti-viral and pro-inflammatory responses leading to activation and proliferation of HIV target cells. Immune modulators that boost anti-viral and depress pro-inflammatory immune responses may decrease HIV-1 infection or replication. Polyinosinic:polycytidylic [Poly (I:C)] has been reported to down-regulate HIV-1 replication in immune cell subsets and lymphoid tissues, yet the scope and mechanisms of poly (I:C) regulation of HIV-1 replication in the cervicovaginal mucosa, the main portal of viral entry in women remain unknown. Using a relevant, underexplored ex vivo cervical tissue model, we demonstrated that poly (I:C) enhanced Interferon Regulatory Factor (IRF)7 mediated antiviral responses and decreased tissue Nuclear Factor Kappa B (NFκB) RNA expression. This pattern of cellular transcription factor expression correlated with decreased HIV-1 transcription and viral release. Reducing IRF7 expression up-regulated HIV-1 and NFκB transcription, providing proof of concept for the critical involvement of IRF7 in cervical tissues. By combining poly (I:C) with a suboptimal concentration of tenofovir, the leading anti-HIV prophylactic microbicide candidate, we demonstrated an earlier and greater decrease in HIV replication in poly (I:C)/tenofovir treated tissues compared with tissues treated with tenofovir alone, indicating overall improved efficacy. Poly (I:C) decreases HIV-1 replication by stimulating IRF7 mediated antiviral responses while reducing NFκB expression. Early during the infection, poly (I:C) improved the anti-HIV-1 activity of suboptimal concentrations of tenofovir likely to be present during periods of poor adherence i.e. inconsistent or inadequate drug use. Understanding interactions between anti-viral and pro-inflammatory immune responses in the genital mucosa will provide crucial insights for the identification of targets that can be harnessed to develop preventative combination strategies to improve the efficacy of topical or systemic antiviral prophylactic agents and protect women from HIV-1 and other sexually transmitted infections.

Electrical conduction mechanism of poly(3,4-ethylenedioxythiophene) nanofiber bundles at low temperature

The nature of charge transport mechanism in poly(3,4-ethylenedioxythiophene) nanofiber bundles has been studied as a function of temperature, magnetic field and AC electric field. High-resolution transmission electron micrographs show the formation of nanofibers with an average diameter of 14 nm. X-ray diffraction analysis depicts the enhancement of polymer chains ordering with increasing dopant concentration. Analysis of the temperature dependence of resistivity reveals a three-dimensional variable range hopping electrical conduction mechanism in the synthesized nanofibers system. A large positive magnetoresistance has been observed at low temperature, which shows a decreasing trend with increasing temperature as well as dopant concentration. The high value of positive magnetoresistance at low temperature has been explained by the wave function shrinkage model. The decrease in frequency exponent s with increasing temperature suggests that the AC conduction takes place through correlated barrier hopping mechanism.

Effect and mechanism of poly (ADP-ribose) polymerase-1 in aldosterone-induced apoptosis

The present study aimed to investigate the effects of aldosterone on vascular endothelial cells and the viability of poly (ADP-ribose) polymerase 1 (PARP1) in cells, and to examine the molecular mechanisms underlying the effects of aldosterone on vascular endothelial cell injury. Cultured endothelial cells were treated either with different concentrations of aldosterone for the same duration or with the same concentrations of aldosterone for different durations, and the levels of apoptosis and activity of PARP1 in the cells were detected, respectively. Aldosterone receptor antagonists or PARP1 inhibitors were added to cells during treatment with aldosterone and the levels of apoptosis and activity of PARP1 were detected. As the concentration of aldosterone increased or the treatment time increased, the number of apoptotic cells and the activity of PARP1 increased. The aldosterone receptor antagonists and PARP1 inhibitors inhibited the increase of apoptosis and PARP1 activity caused by aldosterone treatment. Aldosterone activated the activity of PARP1 via the aldosterone receptor, inhibiting cell proliferation and inducing apoptosis. Treatment with PARP1 may be used as a target for vascular diseases caused by aldosterone at high concentrations.

Dehydrogenation mechanism of LiBH4 by Poly(methyl methacrylate)

We investigated the dehydrogenation properties and mechanism of Poly(methyl methacrylate) (PMMA) confined LiBH4. Thermal stability of LiBH4 was reduced by PMMA, with a decrease in dehydrogenation temperature by 120°C. At 360°C, the composite showed fast dehydrogenation kinetics with 10wt.% of hydrogen released within 1h. The improved dehydrogenation performance was mainly attributed to the reaction between LiBH4 and PMMA forming Li3BO3 as a final product. Furthermore, the presence of electrostatic interaction between B atom of LiBH4 and O atom in the carbonyl group of PMMA may weaken the BH bonding of [BH4]− and lower the hydrogen desorption temperature.

Determination of the mechanism behind the organic magnetoresistance (OMAR) effect by using impedance spectroscopy

We investigated the organic magnetoresistance (OMAR) mechanism in poly(3–hexylthiophene–2,5–diyl) (P3HT)–based diodes, by using impedance spectroscopy. We have prepared layered structures consisting of indium tin oxide, poly(3,4–ethylenedioxythiophene):poly(styrenesulphonate) (PEDOT:PSS), P3HT and aluminium and measured the bias voltage dependence of the OMAR and of the impedance spectra. The capacitance deduced from the impedance data indicated that the OMAR was explained by the single–carrier (bipolaron) model at lower bias voltages as well as double–carrier models at higher bias voltages. The impedance response also suggested that the OMAR from the single–carrier model was governed by the PEDOT:PSS/P3HT interface whereas the double–carrier OMAR was mainly related to the P3HT layer.

Separation of Fe(II) by the DEMI and TEMPO Oxidized Cellulose

The description of some adsorption properties and behaviour of oxycellulose with Fe2+ ions is presented. Filter media from oxycelluloses materials have enormous sorption activity. There is described a sorption mechanism of poly 1,4-β-D anhydroglucuronic acid (PAGA). Utilisation of UV-VIS spectroscopy is shown on the adsorption process of optimalisation of oxycelluloses application. Supporting influence is demonstrated on the adsorption isotherms of Fe2+ ions in the competitive environment of NaCl, MgCl2.

New Mechanism in Anti Tumor Activity of Poly (I:C): Modulation of Tumor-Associated Myeloid Derived Suppressor Cells in Murine Model of Breast Cancer

Background: Polyinosinic- polycytidilic acid {Poly (I:C)} a ligand for TLR-3, has potents effects on activating CD8+ T cells and NK cells and has been used as an immunotherapy adjuvant. Although it is thought TLR-3 signaling is crucial for enhancing cell-mediated immune responses, the effect of Poly (I:C) on immunosuppressive Myeloid derived suppressor cells (MDSC) in tumor-bearing animal is not known. MDSCs are one of the main immunosuppressive factors in cancer, and abnormal accumulation of MDSCs an important mechanism of tumor immune evasion. Here, we describe a novel mechanism for the immuno-stimulatory activity of Poly (I:C): a dramatic reduction of absolute numbers of tumor-infiltrating MDSCs and reduced immunosuppressive function of MDSCs.Methods: 4T1-luciferase tumor cells were implanted into mammary glands of female BALB/c mice (1´106 cells per mouse, n = 5/group). Poly (I:C) was administrated on day 7th (200 mg/mouse) and day 10th (100 mg/mouse) after tumor inoculation (D0), continued with one boost dose. Tumor growth was monitored by bioluminescent imaging (BLI) measuring total photon flux. Mice were euthanized when tumors had reached to 100-200 mm3. Flow cytometry measured CD11b+ Gr-1+ MDSC, and T-cells in the tumors of tumor-bearing mice.Results: Treatment with Poly I:C increased overall survival accompanied by a reduction in tumor burden as measured by total flux/s (p =0.0217) and numbers of MDSCs in ressected tumor samples (p=0.0286). 4T1 tumors grew more slowly in Poly (I:C) treated mice vs PBS-treated group with the lower numbers of CD11b+Gr-1+ cells in Poly (I:C)- treated animals (Figure1). Both granulocytic and monocytic subsets of tumor infiltrating MDSCs (CD11b+ Gr-1+, and Ly6G+/hi or Ly6C+/hi) and CD11b+ Gr-1+ F4/80+ macrophages were significantly reduced of multiple time points after Poly (I:C) treatment compared with control mice. The decrease in MDSC subsets was paralleled with a significant increase in tumor –infiltrating T cells (TIL)s and decreased numbers of CD4+ CD25+ Foxp3+ T regulatory in the tumor. Moreover, Poly (I:C) treatment significantly increased the percentage of CD4+ and CD8+ TNF-a+ T cells in spleen of tumor-bearing mice after reactivation with anti CD3/CD28 antibody. Intracellular staining of pro inflammatory cytokines in splenocyte- derived MDSCs showed higher amount of TNF-a and IL-1b, 5 days after Poly (I:C) treatment indicating MDSCs differentiation into M1 macrophage. Purified splenocyte-derived MDSCs co-cultured with Poly (I:C) (20 mg/ml) showed significant increase in mean fluorescence index (MFI) for MHC class II and co-stimulatory molecules CD80 and CD86 supporting increase d effectiveness as APC.Discussion: These data demonstrate a new mechanism of Poly (I:C) that can lead to alterations in numbers and differentiation of MDSCs resulting in increasing local response of the immune system to tumor with concomitant decrease in tumor volume in a murine model of breast cancer. Also our data support the hypothesis that Poly (I:C) has global effects on the immunosuppressive network in the tumor micro-environment. Considering the role of MDSCs in cancer promotion and backed by data showing alteration in MDSCs quantity and function in 4T1-tumor-bearing hosts, Poly (I:C) treatment can effectively augment the activity of cancer immunotherapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PH Alters PEG-Mediated Fusion of Phosphatidylethanolamine-Containing Vesicles

Here, we examine the different mechanisms of poly(ethylene glycol)-mediated fusion of small unilamellar vesicles composed of dioleoylphosphatidylcholine/dioleoylphosphatidylethanolamine (DOPE)/sphingomyelin/cholesterol in a molar ratio of 35:30:15:20 at pH 7.4 versus pH 5. In doing so, we test the hypothesis that fusion of this lipid mixture should be influenced by differences in hydration of DOPE at these two pH values. An examination of the literature reveals that DOPE should be less hydrated at pH 5 (where influenza virus particles fuse with endosome membranes) than at pH 7.4 (where synaptic vesicles or HIV virus particles fuse with plasma membrane). Ensemble kinetic experiments revealed substantial differences in fusion of this plasma membrane mimetic system at these two pH values. The most dramatic difference was the observation of two intermediates at pH 5 but loss of one of these fusion intermediates at pH 7.4. Analysis of data collected at several temperatures also revealed that formation of the initial fusion intermediate (stalk) was favored at pH 7.4 due to increased activation entropy. Our observations support the hypothesis that the different negative intrinsic curvature of DOPE can account for different fusion paths and activation thermodynamics in steps of the fusion process at these two pH values. Finally, the effects of 2 mol % hexadecane on fusion at both pH values seemed to have similar origins for step 1 (promotion of acyl chain or hydrocarbon excursion into interbilayer space) and step 3 (reduction of interstice energy leading to expansion to a critical stalk radius). Different hexadecane effects on activation thermodynamics at these two pH values can also be related to altered DOPE hydration. The results support our kinetic model for fusion and offer insight into the critical role of phosphatidylethanolamine in fusion.