1,401 research outputs found

    A green product design framework based on quality function deployment process.

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    Internet Self-Efficacy, Self-Regulation, and Student Performance: African-American Adult Students in Online Learning

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    The paper intended to investigate adult students’ Internet self-efficacy, self-regulation, and performance in online learning environments. The relationships between these variables and the effect of student characteristics on Internet self-efficacy and self-regulation were explored. The participants of this study were African American students from a university in the United States. They participated in two web-based research courses offered in summer. Data were collected through an online survey and were analyzed by a quantitative approach. The results showed Internet self-efficacy was positively related to self-regulation at a significant level. Internet selfefficacy and self-regulation differed in terms of student performance. The differences of gender and age did not have a significant impact on Internet self-efficacy and self-regulation. Discussions and implications were addressed according to the major findings of this study

    Immune modulating functions by soypeptide lunasin in cancer immunotherapy

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    Chemotherapy is currently the mainstay of treatment for most cancer patients. Despite its efficacy in eliminating cancer cells, a high percentage of chemotherapy patients eventually relapse or suffer progression of the disease. Immunosurveillance is capable of recognizing and eliminating continuously arising transformed mutant cells, and thus cancer immunotherapy is one of the emerging therapeutic strategies that harnesses the power of the immune system to eradicate chemotherapy-resistant cancerous cells. However, the adverse side effects of chemotherapy impede the therapeutic effects of immunotherapy. Our previous studies demonstrate that lymphoma patients are refractory to clinical immunotherapy because of chemotherapy-induced immune dysfunction. In addition, tumors can induce immune suppression, which allows them to escape immunosurveillance. Thus, it is prudent to develop an efficacious immunotherapy that would enhance anti-tumor immunity in cancer patients who are most often immunodeficient. Lunasin, a 43-amino acid peptide, was originally isolated from soybeans. The current study discovered a novel function of lunasin as a vaccine adjuvant, which enhanced the development of protective immune responses to soluble vaccine antigens. It was found that lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when compared with a medium-only control in the mixed leukocyte reaction (MLR). In addition, lunasin enhanced cross-presentation of soluble antigens by mouse CD11c+DCs and CD8α+DCs, resulting in effective priming of antigen-specific IFNγ producing CD8+ T cells. Immunization with etoposide-treated B-lymphoma cells and lunasin provided nearly 100% protection against tumor growth. Furthermore, inclusion of lunasin in the cancer vaccine model prevented tumor relapse after chemotherapy. The immunomodulatory function of lunasin has also been identified in the STAT4 deficiency model. Our previous studies demonstrated that lymphoma patients were refractory to IL-12-based immunotherapy because of chemotherapy-induced immune dysfunctions associated with acquired deficiency of STAT4. To directly determine the requirement for STAT4 in response to lunasin-based cancer vaccination, a syngeneic B-lymphoma in a prophylactic model was utilized to compare the inhibition of tumor growth in wild-type BALB/c (WT) mice versus STAT4 deficient (Stat4-/-) mice. B-lymphoma cells subcutaneously implanted into Stat4-/- mice have similar tumor growth and progression when compared to WT mice. Lunasin-based whole tumor vaccination induces the development of tumor-specific CD4+ and CD8+ T cells in WT and Stat4-/- mice. In conclusion, Stat4-/- mice do not exhibit accelerated subcutaneous tumor growth over WT mice following lunasin-based vaccination in a syngeneic B-lymphoma model. Collectively, these studies provide the evidence for lunasin as an immunomodulatory agent that enhances the cross-presentation activity of DCs and promotes antigen-specific antitumor immune responses in cancer immunotherapy

    Mechanisms of Gene Regulation by Soy Peptide Lunasin in Innate Immune Cells

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    poster abstractLunasin is a seed peptide containing 43 amino acids, originally isolated from soybeans. Recently, a novel function of lunasin was discovered, as it acts as an immune modulating agent regulating gene expression of various innate immune cells. Lunasin strongly activated the expression of genes encoding for type I interferon and inflammatory cytokines. Nonetheless, the molecular mechanisms of lunasin’s gene regulation are relatively unknown. Our current hypothesis states that lunasin is able to induce activation of various transcription factors, resulting in gene expression in immune cells. Human dendritic cells (DCs) or monocytes were purified from peripheral blood mononuclear cells (PBMCs) in order to determine the activation of transcription factors. Phosphorylation of STAT1 and NF-ĸB (p65) were evident in cells treated with lunasin using flow cytometry and Western blotting. The results will ultimately lead to the signaling pathways involved in gene expression regulated by lunasin in innate immune cells. By defining the signaling pathway of lunasin, we can have a better understanding of its application in immune modulation

    Activation of Dendritic Cells by Soypeptide Lunasin: Implication in Vaccine Adjuvant

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    poster abstractAdjuvants enhance the immunogenicity of vaccines and improve the immune responses. Although many adjuvants are currently used in research, FDA approved aluminum salt (Alum) remains the most often used in human vaccines. Alum is known to promote the Th2 immune response and enhance antibody production, but is less efficient on eliciting Th1 and CTL cellular responses. Thus, it is prudent to improve the effectiveness of current adjuvants or to develop a novel alternative adjuvant. We have recently identified lunasin, a seed peptide from soybeans, as a novel immune modulator. The objective is to define the effectiveness of lunasin peptide as an adjuvant that can enhance the protective immunity of vaccines. Our studies have revealed stimulatory effects of lunasin on dendritic cells (DCs) by regulating expression of a number of genes that are important for immune responses. Lunasin-treated human conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86) but also exhibited up-regulation of chemokines (CCL2, CCL3, CCL4) and cytokine (IL-1β). To determine the function of lunasin-treated cDCs, these cells were co-cultured with allogeneic human peripheral blood CD4+ T cells for 7 days in the mixed lymphocyte reaction. Lunasin-treated cDCs induced almost 2-fold higher proliferation of allogeneic CD4+ T cells when comparing with a sham treatment. To verify the in vivo effects, lunasin was administered into mice. Increased CD86 expression was found in cDCs from spleens of mice treated with lunasin. Furthermore, mice vaccinated with lunasin-adjuvanted ovalbumin (OVA) had reduced tumor growth following challenging with OVA-expressing A20 B-lymphoma cells. Taken together, our data suggest that lunasin may act as a vaccine adjuvant by targeting DCs to enhance and modulate the immune responses to antigens

    GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing

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    Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base

    Prevalence and Associated Metabolic Factors of Gallstone Disease in the Elderly Agricultural and Fishing Population of Taiwan

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    Purpose. To evaluate sex-related differences in the prevalence of and cardiovascular risk factors related to gallstone disease (GSD) in an elderly agricultural and fishing population of Taipei, Taiwan. Methods. The study sample consisted of 6511 healthy elderly participants (3971 men and 2540 women) who were voluntarily admitted to a teaching hospital for a physical checkup in 2010. The participants’ blood samples and real-time ultrasound fatty liver results were collected. Results. The prevalence of GSD in the study population was 13.2%, which increased significantly with population age (P<.0001). Women were associated with significantly higher GSD prevalence than men (14.8% versus 12.2%; for the chi-square test, P=.003). In a multiple logistic regression analysis, female sex, older age, and metabolic syndrome (MetS) were significantly associated with GSD. Multiple logistic regression analysis also revealed that obesity (odds ratio OR=1.26, 95% confidence interval (CI): 1.09–1.44) and metabolic factors (one or 2 versus none, OR=1.48, 95% CI: 1.08–1.76) were significantly associated with GSD in women but not in men. Conclusion. In the study population, female sex, older age, and MetS were associated with higher GSD prevalence. The population exhibited other sex-related differences

    Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

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    IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations
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