Repression of MUC1 Promotes Expansion and Suppressive Function of Myeloid-Derived Suppressor Cells in Pancreatic and Breast Cancer Murine Models

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing syngeneic pancreatic (KCKO) or breast (C57MG) tumors. We observed enhanced tumor growth of pancreatic and breast tumors in the MUC1KO mice compared to the WT mice. Enhanced tumor growth in the MUC1KO mice was associated with increased numbers of suppressive MDSCs and T regulatory (Tregs) cells in the tumor microenvironment. Compared to the WT host, MUC1KO host showed higher levels of iNOS, ARG1, and TGF-β, thus promoting proliferation of MDSCs with an immature and immune suppressive phenotype. When co-cultured with effector T cells, MDSCs from MUC1KO mice led to higher repression of IL-2 and IFN-γ production by T cells as compared to MDSCs from WT mice. Lastly, MDSCs from MUC1KO mice showed higher levels of c-Myc and activated pSTAT3 as compared to MDSCs from WT mice, suggesting increased survival, proliferation, and prevention of maturation of MDSCs in the MUC1KO host. We report diminished T cell function in the KO versus WT mice. In summary, the data suggest that MUC1 may regulate signaling pathways that are critical to maintain the immunosuppressive properties of MDSCs.     

A study of ageing effect at elevated temperature of flexible silicon diodes integrated using conductive adhesives

A simple fabrication scheme of using silver-filled conductive tape to form flexible single crystalline Si–Pd Schottky diodes on a polymer substrate has been studied and reported previously. In this investigation, we studied the long term thermal stability of these flexible diodes on polymer annealed at 80 °C in open air for 1 year. The I–V characteristics of the diodes were measured periodically. We found that the barrier height of the Si–Pd diodes remained relatively unchanged at 0.795 eV ± 0.003 with an n-factor of 1.03 ± 0.03, and a series resistance of ∼110 Ω for diodes with a 950 μm diameter, which are almost identical to the values before annealing. The integrated structure stayed flexible to a similar curvature after 1 year. The stability of silver-filled conductive tape was investigated separately over the same period of time and under the same conditions. The resistance of two conductive tapes was found to quickly decrease from high initial values to significantly lower values, and remained constant over the course of the investigation. Based on these results, we conclude that this simple bonding technique of using conductive tape to fabricate flexible devices can be of useful value in practical applications.     

From categorization to classification: A comparison among individuals with autism, mental retardation, and normal development.

Free-sorting, matrix, and class-inclusion tasks were administered to 16 participants with autism, 16 participants with mental retardation (MR), and 16 normal children, matched for mental age. On perceptual matrices, participants with MR performed less well than those with autism, who performed less well than normal children. On functional matrices, participants with autism and those with MR performed less well than normal children. Participants with autism performed less well than participants with MR and normal children in free-sorting representational objects and in the class-inclusion tasks, which require higher operational thought. These results suggest that individuals with autism have difficulties with tasks that necessitate internal manipulation of information. This impairment is discussed in relation to the cognitive deficit characterizing autism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Shimming a high-resolution MAS probe

The gene expression and interrelation of the constitutive type nitric oxide (NO) synthase-III as a NO-forming enzyme and heme oxygenase-2 as a carbon monoxide-forming enzyme were studied in cultured rat aortic endothelial cells. Both NO synthase-III and heme oxygenase-2 mRNAs were demonstrated in the endothelial cells by RNAase protection analysis. NO synthase-III mRNA was upregulated in the presence of the heme oxygenase inhibitor, zinc protoporphyrin IX, but not in the presence of the NO synthase inhibitor, N(G)-nitro-L-arginine. Although heme oxygenase-2 mRNA was significantly upregulated in the presence of both NO synthase inhibitor and heme oxygenase inhibitor, the increase was greater with the NO synthase inhibitor. These results provide the first evidence for the concomitant gene expression of NO synthase-III and heme oxygenase-2, and their compensatory interrelation in endothelial cells.     

RF CHOS蓝牙收发器的设计(连载二)

该文介绍了一种设计方法，它是通过使用晶片厂模型、论证测试模板以及与测试仪器的链接，实现RFIC设计并很快获得原型芯片。描述了蓝牙收发器的设计，其中包括，在统一EDA环境下的仿真结果和硬件验证。     

Expert systems for power applications

The author briefly discusses expert systems and the incentives for producing them. He then goes on to discuss applications in the power industry including an energy management system for control of power generation, power transmission, and distribution networks. They are also used for power system security, voltage and transient stability, decisionmaking in design, and for planning scenarios. They are also used for process plant control     

A probabilistic method for the evaluation of coupling betweentransmission lines

The authors point out that the random positioning of wires, as described here, frequently occurs in practice since the relative positions of the wires are often unknown. Consequently, the problem of crosstalk has a probabilistic nature and needs to be analyzed accordingly. The problem of two wires whose heights above ground and whose distance of separation are known only probabilistically is considered. A model enabling the computation of the coupling distribution and other statistical parameters of interest, such as the coupling distribution's expectation and standard deviation, is developed. A simulation was performed, and its results compare well with computations based on the analytical model     

Lack of immunosuppressive effect of low-dose oral methotrexate on lymphocytes in rheumatoid arthritis

Whether methotrexate (MTX) is effective in rheumatoid arthritis (RA) because of immunosuppressive and/or anti-inflammatory mechanisms of action is controversial. Many lines of investigation point to the latter. We evaluated DNA synthesis in peripheral blood lymphocytes (PBL) from 33 RA patients on oral MTX (7.5-15 mg/wk) and in 30 healthy controls by flow cytometric cell cycle analysis (CCA). DNA synthesis was also evaluated with a thymidilate synthetase activity assay (TSA) (3H-deoxyuridine incorporation) in 12 patients and 21 controls (12 on MTX and NSAID, and 9 healthy subjects). The patients had taken MTX for at least 3 months and were in different stages of clinical activity. There were no significant differences in TSA or in the cell cycle phase distributions (especially the S phase) between treated RA patients and controls. These data suggest that low-dose oral MTX does not inhibit DNA synthesis and therefore does not have an immunosuppressive effect on lymphocytes from patients with RA.     

Compound CVT-E002 attenuates allergen-induced airway inflammation and airway hyperresponsiveness, in vivo

Immune modulation has been a sought after means of therapy for atopic diseases. CVT-E002 is an extract derived from North American Ginseng shown to promote T-helper-1-like responses. We determined what effect CVT-E002 could have in a mouse model of atopic asthma. We report that oral CVT-E002 inhibited the development of allergic airway inflammation and airway hyperresponsiveness. This correlated with an increased presence of interferon-γ in the lung, and also increased regulatory T cells and IL-10. The ability of CVT-E002 to induce regulatory T-cell development was also seen in human in vitro co-cultures.     

Food Mycotoxins: An Update

The Institute of Food Technologists has issued this Scientific Status Summary to update readers on the science of fungal toxins.