Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability.     

Progressive ratio schedules of reinforcement.

[Correction Notice: An erratum for this article was reported in Vol 35(2) of Journal of Experimental Psychology: Animal Behavior Processes (see record 2009-05154-003). The URL provided for the supplemental material was incomplete. The complete URL is http://dx.doi.org/10.1037/a0012497.supp] Pigeons' pecks produced grain under progressive ratio (PR) schedules, whose response requirements increased systematically within sessions. Experiment 1 compared arithmetic (AP) and geometric (GP) progressions. Response rates increased as a function of the component ratio requirement, then decreased linearly (AP) or asymptotically (GP). Experiment 2 found the linear decrease in AP rates to be relatively independent of step size. Experiment 3 showed pausing to be controlled by the prior component length, which predicted the differences between PR and regressive ratio schedules found in Experiment 4. When the longest component ratios were signaled by different key colors, rates at moderate ratios increased, demonstrating control by forthcoming context. Models for response rate and pause duration based on Bizo and Killeen (1997) described performance on AP schedules; GP schedules required an additional parameter representing the contextual reinforcement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Torrefied biomass‐polypropylene composites

Torrefied almond shells and wood chips were incorporated into polypropylene as fillers to produce torrefied biomass‐polymer composites. The composites were prepared by extrusion and injection molding. Response surface methodology was used to examine the effects of filler concentration, filler size, and lignin factor (relative lignin to cellulose concentration) on the material properties of the composites. The heat distortion temperatures, thermal properties, and tensile properties of the composites were characterized by thermomechanical analysis, differential scanning calorimetry, and tensile tests, respectively. The torrefied biomass composites had heat distortion temperatures of 8–24°C higher than that of neat polypropylene. This was due to the torrefied biomass restricting mobility of polypropylene chains, leading to higher temperatures for deformation. The incorporation of torrefied biomass generally resulted in an increase in glass transition temperature, but did not affect melting temperature. Also, the composites had lower tensile strength and elongation at break values than those of neat polypropylene, indicating weak adhesion between torrefied biomass and polypropylene. However, scanning electron microscopy results did indicate some adhesion between torrefied biomass and polypropylene. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41582.     

Duality in fuzzy linear programming: a survey

The concepts of both duality and fuzzy uncertainty in linear programming have been theoretically analyzed and comprehensively and practically applied in an abundance of cases. Consequently, their joint application is highly appealing for both scholars and practitioners. However, the literature contributions on duality in fuzzy linear programming (FLP) are neither complete nor consistent. For example, there are no consistent concepts of weak duality and strong duality. The contributions of this survey are (1) to provide the first comprehensive overview of literature results on duality in FLP, (2) to analyze these results in terms of research gaps in FLP duality theory, and (3) to show avenues for further research. We systematically analyze duality in fuzzy linear programming along potential fuzzifications of linear programs (fuzzy classes) and along fuzzy order operators. Our results show that research on FLP duality is fragmented along both dimensions; more specifically, duality approaches and related results vary in terms of homogeneity, completeness, consistency with crisp duality, and complexity. Fuzzy linear programming is still far away from a unifying theory as we know it from crisp linear programming. We suggest further research directions, including the suggestion of comprehensive duality theories for specific fuzzy classes while dispensing with restrictive mathematical assumptions, the development of consistent duality theories for specific fuzzy order operators, and the proposition of a unifying fuzzy duality theory.     

Chemical Composition and Physical Properties of High Oleic Safflower Oils (Carthamus tinctorius,Var. CW88-OL and CW99-OL)

Chemical composition and physical properties of CW88‐OL and CW99‐OL cultivars of high oleic safflower seeds and their hexane‐extracted oils were determined. Dry‐based seed composition of CW88‐OL and CW99‐OL was: moisture = 4.29 and 4.23 %, oil = 42.29 and 46.44 %, Crude protein = 20.94 and 16.41 %, neutral detergent fiber = 28.11 and 28.49 %, ash = 1.55 and 2.01 %, phosphorus content = 2033 and 3995 mg/kg, respectively. Major fatty acids in oils were ~78 % oleic (O), ~13 % linoleic (L), ~5 % palmitic (P) and ~2 % stearic (St) acids, for both cultivars. The main triacylglycerols were OOO (~50 %), OOL (~20 %), SOL + OPO (~10 %), and LLP (~5 %). The oil composition of CW88‐OL and CW99‐OL in main minor components was: α‐tocopherol = 582 and 551 mg/kg, total sterols = 3996 and 3362 mg/kg, phospholipids = 22 and 21 mg/kg and wax content = 70 and 74 mg/kg. For both cultivars, density and viscosity of the oils between 25 and 55 °C varied from 903.4 to 912.6 kg/m³ and 63 to 23 mPa.s showing linear and exponential behaviors, respectively. The refractive index was 1.4694. The CIELab color parameters were: 89.69 and 89.53 (L*), ?3.72 and ?3.07 (a*), and 47.28 and 47.78 (b*) (CW88‐OL and CW99‐OL, respectively). Thus, the high oil content of the seeds and nutritional quality of the oil accompanied by low levels of waxes and phospholipids makes the cultivars studied promising for producers and consumers.     

Proximate Composition and Seed Lipid Components of Sorghum Cultivars from Argentina

Seeds of 11 sorghum cultivars ( Sorghum bicolor ) from Argentina were analysed for proximate composition, fatty acids and sterols. Oil, protein, carbohydrate and ash contents varied between 41 and 66 g kg⁻¹, 111 and 156 g kg⁻¹, 670 and 730 g kg⁻¹ and 13·8 and 20·6 g kg⁻¹ of dry matter, respectively. Fatty acid profiles revealed that the major acids were palmitic (15·1–24·8%), oleic (29·9–41·8%) and linoleic (35·9–51·3%). Unsaponifiable matter was examined for sterols. Sitosterol was the prominent component in all cultivars (43·8–57·9%), followed by campesterol (18·7–29·1%) and stigmasterol (12·4–20·5%).     

Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells

Melanoma is the deadliest form of skin cancer, and its incidence has alarmingly increased in the last few decades, creating a need for novel treatment approaches. Thus, we evaluated the combinatorial effect of doxorubicin (DOX) and hyperthermia on A375 and MNT-1 human melanoma cell lines. Cells were treated with DOX for 24, 48, and 72 h and their viabilities were assessed. The effect of DOX IC10 and IC20 (combined at 43 °C for 30, 60, and 120 min) on cell viability was further analyzed. Interference on cell cycle dynamics, reactive oxygen species (ROS) production, and apoptosis upon treatment (with 30 min at 43 °C and DOX at the IC20 for 48 h) were analyzed by flow cytometry. Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration. Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels. Additionally, it induced early apoptosis in MNT-1 cells, while in A375 cells this effect was similar to the one caused by hyperthermia alone. These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.     

Evaluation of Oxidative Stress Biomarkers,Pro-Inflammatory Cytokines,and Histological Changes in Experimental Hypertension,Dyslipidemia, and Type 1 Diabetes Mellitus

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.     

How the Influence of Different Salts on Interfacial Properties of Surfactant–Oil–Water Systems at Optimum Formulation Matches the Hofmeister Series Ranking

In this work, we present the effects of salts on sodium dodecyl benzene sulfonate micellization and on the interfacial performance of a sodium dodecyl benzene sulfonate–heptane–brine system at optimum formulation, i.e., hydrophilic–lipophilic deviation (HLD) = 0. In order to do that, interfacial tension and dilational interfacial rheology properties of surfactant–heptane–water systems at optimum formulation are measured using an interfacial spinning drop tensiometer with an oscillating velocity, which can accurately measure interfacial rheology properties at both low and ultralow interfacial tensions. The brines used contain one of the following salts: MgCl₂, CaCl₂, NaCl, NH₄Cl, NaNO₃, CH₃COONa, or Na₂SO₄. We performed a one-dimensional salinity scan with each of these salts to achieve an optimum formulation. In relation to the Hofmeister series, we found that, at optimum formulation, systems with chaotropic ions (NH₄⁺, NO₃⁻) present interfaces with ultralow interfacial tensions, very low dilational modulus, and a low phase angle, whereas kosmotropic ions (Mg²⁺, Ca²⁺, SO₄⁻²) generate high interfacial tension and high rigidity monolayers. Intermediate ions in the Hofmeister series (Na⁺, CH₃COO⁻, Cl⁻) present interfaces with intermediate properties. Furthermore, according to the Hofmeister series, interfaces can be respectively ordered from higher to lower rigidity for surfactant counterions Mg²⁺ > Ca²⁺ > Na⁺ > NH₄⁺ and coions SO₄²⁻ > CH₃COO^– > Cl⁻ > NO₃⁻, which correspond to a salting-out (highest rigidity) and salting-in (lowest rigidity) effect. We observed that counterions have a more significant effect on surfactant–oil–water system properties than those that act as coions.     

Osteonecrosis of the Jaws in Patients with Hereditary Thrombophilia/Hypofibrinolysis—From Pathophysiology to Therapeutic Implications

Osteonecrosis of the jaws (ONJ) usually has a clear etiology. Local infection or trauma, radiotherapy and drugs that disrupt the vascular supply or bone turnover in the jaws are its major contributors. The thrombotic occlusion of the bone’s venous outflow that occurs in individuals with hereditary thrombophilia and/or hypofibrinolysis has a less known impact on jaw health and healing capability. Our research provides the most comprehensive, up-to-date and systematized information on the prevalence and significance of hereditary thrombophilia and/or hypofibrinolysis states in ONJ. We found that hereditary prothrombotic abnormalities are common in patients with ONJ refractory to conventional medical and dental treatments. Thrombophilia traits usually coexist with hypofibrinolysis traits. We also found that frequently acquired prothrombotic abnormalities coexist with hereditary ones and enhance their negative effect on the bone. Therefore, we recommend a personalized therapeutic approach that addresses, in particular, the modifiable risk factors of ONJ. Patients will have clear benefits, as they will be relieved of persistent pain and repeated dental procedures.