Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo

Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a “proof of concept” vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage

Dual threshold diode based on the superconductor-to-insulator transition in ultrathin TiN filmss

We investigate transport properties of superconducting TiN films in the vicinity of the superconductor-insulator transition (SIT). We show that the current-voltage (I-V) characteristics are mirror-symmetric with respect to the SIT and can be switched to each other by the applied magnetic field. In both superconducting and insulating states, the low-temperature I-V characteristics have pronounced diode-like threshold character, demonstrating voltage/current jumps over several orders of magnitude at the corresponding critical current or threshold voltage. We have found that for both states, the theory developed for Josephson junction arrays offers a quantitative description of the experimental results

A novel IgE antibody targeting the prostate-specific antigen as a potential prostate cancer therapy

Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 andCD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa.Fil: Daniels-Wells, Tracy R. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Leuchter, Richard K. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Quintero, Rafael. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Kozman, Maggie. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Rodríguez, José A.. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; University of California. The Molecular Biology Institute; Estados Unidos de América;Fil: Ortiz-Sánchez, E. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; Biomedical Research in Cancer. Basic Research Division. National Institute of Cancerology; Mexico.;Fil: Martínez-Maza, Otonel. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Schultes, Brigit C.. Advanced Immune Therapeutics; Estados Unidos de América;Fil: Nicodemus Christopher. Advanced Immune Therapeutics; Estados Unidos de América;Fil: Penichet, Manuel. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; University of California. The Molecular Biology Institute; Estados Unidos de América

Plasmapheresis in the Treatment of Hypertriglyceridemia-Induced Pancreatitis: A Community Hospital's Experience

Background: Hyperlipidemic pancreatitis is a potentially fatal complication of hypertriglyceridemia (HTG). The current mainstay of treatment for the hypertriglyceridemia associated with pancreatitis includes heparin, insulin and lipid lowering agents. Experiences with plasmapheresis are limited. Here, we report our experience using plasmapheresis in the treatment of four patients with acute severe HTG-induced pancreatitis. Methods: Four patients with acute severe HTG-induced pancreatitis due to severe primary hyperlipidemia exacerbated by secondary factors were studied. In addition to the standard treatment (insulin or heparin infusion), antibiotics and lipid lowering agents, two were treated within the first 48 hours, and two with early (<24 hours) plasmapheresis with 5% albumin. Results: All four patients had a significant improvement in their triglyceride levels using plasmapheresis with an average reduction in TG levels of 70.4c/o per treatment and 89.3% with the first treatment. However, there was no clear relation between the use of plasmapheresis and either improvement in APACHE II scores, length of stay in either the ICU or overall hospital length of stay or in the prevention of complications secondary to severe pancreatitis, including in the two patients who received plasmapheresis in the first 24 hours. Conclusion: Our report showed that plasmapheresis was successful in lowering TG levels. However, in the absence of a comparison with standard treatment (heparin or insulin infusion and lipid lowering. agents) the effect of plasmapheresis on lowering the morbidity and length of stay of patients with HTG-induced acute severe pancreatitis is uncertain and warrants further investigation into its efficacy. J. Clin. Apheresis 25:229-234, 2010. (C) 2010 Wiley-Liss, Inc

Magnetic, electrical, thermal transport, and thermoelectric proberties of the ... and ... complex metallic alloy phases in the Al-Pd-Mn system

The Al-Pd-Mn system of intermetallics contains complex metallic alloy (CMA) phases, whose crystal structures are based on giant unit cells comprising up to more than a thousand atoms per cell. We performed investigation of the magnetic, electrical, and thermal transport and thermoelectric properties of the xi(') phase and the related Psi phase on single-crystalline samples grown by the Bridgman technique. The samples are diamagnets with a tiny paramagnetic Curie-like magnetization and an estimated fraction of magnetic Mn atoms about 100 ppm. The electrical resistivity between 300 and 4 K exhibits a temperature variation of less than 2%. The origin of this temperature-compensated resistivity is analyzed in terms of the spectral conductivity model. The thermal conductivity of the samples is small and can be described by the sum of the electronic and lattice contributions, which are of comparable size at room temperature. The lattice contribution can be reproduced by the sum of the Debye term (long-wavelength phonons) and the term due to hopping of localized vibrations. The thermoelectric power is small and negative, compatible with a low concentration of electrons as the majority charge carriers. The studied physical properties of the giant-unit-cell CMA phases in the Al-Pd-Mn system are in many respects intermediate between those of metals or simple intermetallics and quasicrystals, suggesting that both the polytetrahedral local atomic order and the large-scale periodicity influence the physical properties of the material

Cancer vaccines: Enhanced immunogenic modulation through therapeutic combinations

Therapeutic cancer vaccines have gained significant popularity in recent years as new approaches for specific oncologic indications emerge. Three therapeutic cancer vaccines are FDA approved and one is currently approved by the EMA as monotherapy with modest treatment effects. Combining therapeutic cancer vaccines with other treatment modalities like radiotherapy (RT), hormone therapy, immunotherapy, and/or chemotherapy have been investigated as a means to enhance immune response and treatment efficacy. There is growing preclinical and clinical data that combination of checkpoint inhibitors and vaccines can induce immunogenic intensification with favorable outcomes. Additionally, novel methods for identifying targetable neoantigens hold promise for personalized vaccine development. In this article, we review the rationale for various therapeutic combinations, clinical trial experiences, and future directions. We also highlight the most promising developments that could lead to approval of novel therapeutic cancer vaccines

Loss of e-cadherin and retinoblastoma genes in a case of urothelial carcinoma with scrotal metastasis

Cutaneous metastases from urologic cancers are very uncommon, usually represent widespread metastatic disease and are associated with a very poor prognosis. They may occur in 1% of patients with urologic malignancies, most commonly from kidney, followed by bladder and prostate tumors. In this report, we describe a case of urothelial carcinoma with metastases to the scrotum treated with platinum based chemotherapy with a durable complete response lasting more than 14 months. Molecular profiling revealed deleterious mutations in e-cadherin and retinoblastoma genes, suggesting their possible role in the pathogenesis of cutaneous metastases. Further studies are needed to validate this observation

Electrical, magnetic, thermal and thermoelectric properties of the "Bergman phase" Mg32(Al,Zn)49 complex metallic alloy

The Mg-Al-Zn system of intermetallics contains an exceptional crystalline phase Mg-32(Al,Zn)(49), named the Bergman phase, whose crystal structure is based on a periodic arrangement of icosahedral Bergman clusters within the giant-unit-cell, so that periodic and quasiperiodic atomic orders compete in determining the physical properties of the material. We have investigated electrical, magnetic, thermal and thermoelectric properties of a monocrystalline Bergman phase sample of composition Mg-29.4(Al,Zn)(51.6), grown by the Bridgman technique. Electrical resistivity is in the range rho approximate to 40 mu Omega cm and exhibits positive-temperature-coefficient with V dependence at low temperatures and T at higher temperatures, resembling non-magnetic amorphous alloys. Magnetic susceptibility x measurements revealed that the sample is a Pauli paramagnet with a significant Landau diamagnetic orbital contribution. The susceptibility exhibits a weak increase towards higher temperature. Combined analysis of the rho(T) and chi(T), together with the independent determination of the Pauli susceptibility via the NMR Knight shift suggests that the observed temperature dependence originates from the mean-free-path effect on the orbital susceptibility. The electronic density of states (DOS) at the Fermi energy E-F was estimated by NMR and was found to amount 72% of the DOS of the fee Al metal, with no evidence on the existence of a pseudogap. Thermal conductivity contains electronic, Debye and hopping of localized vibrations terms, whereas thermopower is small and negative. High structural complexity of the Bergman phase does not result in high complexity of its electronic structure. (c) 2006 Elsevier B.V. All rights reserved

Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis

Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis. The rationale for a combined molecule is to block the PD-1/PD-L1 interaction between tumor cells and immune cell infiltrate and simultaneously reduce or eliminate TGFβ from the tumor microenvironment. In this study, we explored the effect of M7824 on invasive urothelial carcinoma cell lines