Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous T_helper peptide, and a TLR2 (Pam₃CysSK₄) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam₃CysSK₄‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam₃CysSK₄, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 .     

Influence of silver nanoparticle addition,porosity, and processing technique on the mechanical properties of Ba0.3Co4Sb12 skutterudites

The thermoelectric skutterudite Ba_0.3Co₄Sb₁₂ is a promising candidate for waste heat recovery applications. Recently, it was demonstrated that the addition of silver nanoparticles (Ag_NP) to Ba_0.3Co₄Sb₁₂ increases both the thermoelectric figure of merit and electrical conductivity. This study is the first to examine the effect of Ag_NP addition on the material’s mechanical properties. This study also found that the Young’s modulus, E, shear modulus, G, and bulk modulus, B, decreased linearly with increasing volume fraction porosity, P. Resonant ultrasound spectroscopy was employed to measure the elastic moduli, and Vickers indentation was used to determine the hardness, H, and fracture toughness, K _C. Trends in the mechanical properties as a function of grain size, porosity, and the Ag_NP are discussed in terms of the pertinent literature. While K _C was independent of Ag_NP addition, porosity, and grain size, both E and H decreased linearly with increasing porosity. In addition, this study is the first to identify (i) the Ag₃Sb phase formed and (ii) the enhanced densification that occurs when the Ag_NP is sintered with Ba_0.3Co₄Sb₁₂ powders, where both effects are consistent with the eutectic and peritectic reactions observed in the binary phase diagram Ag–Sb. These eutectic/peritectic reactions may also be linked to the enhancement of electrical conductivity previously observed when Ag is added to Ba_0.3Co₄Sb₁₂. Also, similar beneficial eutectic/peritectic reactions may be available for other systems where conductive particles are added to other antimonides or other thermoelectric systems.     

Synthesis of Brightly PEGylated Luminescent Magnetic Upconversion Nanophosphors for Deep Tissue and Dual MRI Imaging

A method is developed to fabricate monodispersed biocompatible Yb/Er or Yb/Tm doped β‐NaGdF₄ upconversion phosphors using polyelectrolytes to prevent irreversible particle aggregation during conversion of the precursor, Gd₂O(CO₃)₂?H₂O:Yb/Er or Yb/Tm, to β‐NaGdF₄:Yb/Er or Yb/Tm. The polyelectrolyte on the outer surface of nanophosphors also provided an amine tag for PEGylation. This method is also employed to fabricate PEGylated magnetic upconversion phosphors with Fe₃O₄ as the core and β‐NaGdF₄ as a shell. These magnetic upconversion nanophosphors have relatively high saturation magnetization (7.0 emu g^?1) and magnetic susceptibility (1.7 × 10^?2 emu g^?1 Oe^?1), providing them with large magnetophoretic mobilities. The magnetic properties for separation and controlled release in flow, their optical properties for cell labeling, deep tissue imaging, and their T₁‐ and T₂‐weighted magnetic resonance imaging (MRI) relaxivities are studied. The magnetic upconversion phosphors display both strong magnetophoresis, dual MRI imaging (r₁ = 2.9 mM^?1 s^?1, r₂ = 204 mM^?1 s^?1), and bright luminescence under 1 cm chicken breast tissue.     

See-saw rocking: an in vitro model for mechanotransduction research

In vitro mechanotransduction studies, uncovering the basic science of the response of cells to mechanical forces, are essential for progress in tissue engineering and its clinical application. Many varying investigations have described a multitude of cell responses; however, as the precise nature and magnitude of the stresses applied are infrequently reported and rarely validated, the experiments are often not comparable, limiting research progress. This paper provides physical and biological validation of a widely available fluid stimulation device, a see-saw rocker, as an in vitro model for cyclic fluid shear stress mechanotransduction. This allows linkage between precisely characterized stimuli and cell monolayer response in a convenient six-well plate format. Models of one well were discretized and analysed extensively using computational fluid dynamics to generate convergent, stable and consistent predictions of the cyclic fluid velocity vectors at a rocking frequency of 0.5 Hz, accounting for the free surface. Validation was provided by comparison with flow velocities measured experimentally using particle image velocimetry. Qualitative flow behaviour was matched and quantitative analysis showed agreement at representative locations and time points. Maximum shear stress of 0.22 Pa was estimated near the well edge, and time-average shear stress ranged between 0.029 and 0.068 Pa. Human tenocytes stimulated using the system showed significant increases in collagen and GAG secretion at 2 and 7 day time points. This in vitro model for mechanotransduction provides a versatile, flexible and inexpensive method for the fluid shear stress impact on biological cells to be studied.     

Residential fuelwood consumption in the Southeastern U.S.

A telephone survey of households in 13 states in the southeastern U.S. determined residential fuelwood acquisition and use for heating during the 1991 heating season. Although wood burning accounted for only 10% of the total household heat requirement of the region, it accounted for 51% of the total heat requirements of wood-burning households. One-quarter (25%) of the households burned wood, consuming almost 9 million standard cords. Three-quarters (77%) of wood-burning households reported that wood burning contributed to household heating requirements. Wood as a source of home heating was particularly important to low income households, both rural and urban. Wood is the sole source of home heating for 17% of the wood-burning households in the region.     

The origin of the Cerro Prieto geothermal brine

The Cerro Prieto geothermal brine may have originated from mixing of Colorado River water with seawater evaporated to about six times its normal salinity. This mixture circulated deeply and was heated by magmatic processes. During deep circulation, Li, K, Ca, B, SiO₂ and rare alkalis were transferred from rock minerals to the water, and Mg, SO₄, and a minor quantity of Na were transferred to the rock. Similar alteration of seawater salt chemistry has been observed in coastal geothermal systems and produced in laboratory experiments. After heating and alteration the brine was further diluted to its present range of composition. Oxygen isotopes in the fluid are in equilibrium with reservoir calcite and have been affected by exploitation-induced boiling and dilution.     

A research note on factors affecting the determination of myofibrillar fragmentation

The myofibrillar fragmentation index (MFI) was determined for a section of ovine Longissimus muscle, aged for either 1 or 3 days and processed from either the fresh or frozen state. Additionally samples were homogenized at one of three speeds (5000, 10,000 or 15,000 rpm). Speed of homogenisation and 'state' of the sample both had a significant effect (P < 0.001) on MFI values as did the interaction between speed and state (P < 0.001), with other interactions terms not being significant. Age of the sample had no significant (P > 0.05) effect on MFI values with least square means (s.e.) for Day 1 and Day 3 being 92 and 93 (1.16), respectively. As homogenisation speed increased, the difference between values for fresh and frozen samples was diminished, such that at 15,000 rpm there was no effect of 'state' on values. Overall the 'state' and the speed of homogenisation have a large impact on values and there was more variation between samples at the slowest speed (5000 rpm). At the slowest speed myofibrils consist of more sarcomeres and can be observed to still exhibit intermyofibril linkages. The results suggest a homogenisation speed of 15,000 rpm was preferable when determining MFI values.