Mechanics IUTAM USNC/TAM a history of people, events, and communities

CERN Document Server

Herakovich, Carl T

2016-01-01

This book provides a detailed history of the United States National Committee on Theoretical and Applied Mechanics (USNC/TAM) of the US National Academies, the relationship between the USNC/TAM and IUTAM, and a review of the many mechanicians who developed the field over time. It emphasizes the birth and growth of USNC/TAM, the birth and growth of the larger International Union of Theoretical and Applied Mechanics (IUTAM), and explores the work of mechanics from Aristotle to the present. Written by the former Secretary of USNC/TAM, Dr. Carl T. Herakovich of the University of Virginia, the book profiles luminaries of mechanics including Galileo, Newton, Bernoulli, Euler, Cauchy, Prandtl, Einstein, von Kármán, Timoshenko, and in so doing provides insight into centuries of scientific and technologic advance. Profiles the applied mathematicians and engineers who developed the field of mechanics in the context of the establishment of the USNC/TAM and the IUTAM Details the relationship between USNC/TAM and IUTAM ...

The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

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Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

2012-10-18

Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome.

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Roy, Anindita; Roberts, Irene; Vyas, Paresh

2012-08-01

Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically 'silent'. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS. Copyright © 2012 Elsevier Ltd. All rights reserved.

GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.

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Law, Luke A; Graham, Douglas K; Di Paola, Jorge; Branchford, Brian R

2018-01-01

The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.

Thioredoxin 80-Activated-Monocytes (TAMs) Inhibit the Replication of Intracellular Pathogens

DEFF Research Database (Denmark)

Cortes-Bratti, Ximena; Brasseres, Eugenie; Herrera-Rodriquez, Fabiola

2011-01-01

Background: Thioredoxin 80 (Trx80) is an 80 amino acid natural cleavage product of Trx, produced primarily by monocytes. Trx80 induces differentiation of human monocytes into a novel cell type, named Trx80-activated-monocytes (TAMs). Principal Findings: In this investigation we present evidence...... for a role of TAMs in the control of intracellular bacterial infections. As model pathogens we have chosen Listeria monocytogenes and Brucella abortus which replicate in the cytosol and the endoplasmic reticulum respectively. Our data indicate that TAMs efficiently inhibit intracellular growth of both L...... in TAMs compared to that observed in control cells 24 h post-infection, indicating that TAMs kill bacteria by preventing their escape from the endosomal compartments, which progress into a highly degradative phagolysosome. Significance: Our results show that Trx80 potentiates the bactericidal activities...

The Structure of a Conserved Domain of TamB Reveals a Hydrophobic β Taco Fold.

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Josts, Inokentijs; Stubenrauch, Christopher James; Vadlamani, Grishma; Mosbahi, Khedidja; Walker, Daniel; Lithgow, Trevor; Grinter, Rhys

2017-12-05

The translocation and assembly module (TAM) plays a role in the transport and insertion of proteins into the bacterial outer membrane. TamB, a component of this system spans the periplasmic space to engage with its partner protein TamA. Despite efforts to characterize the TAM, the structure and mechanism of action of TamB remained enigmatic. Here we present the crystal structure of TamB amino acids 963-1,138. This region represents half of the conserved DUF490 domain, the defining feature of TamB. TamB 963-1138 consists of a concave, taco-shaped β sheet with a hydrophobic interior. This β taco structure is of dimensions capable of accommodating and shielding the hydrophobic side of an amphipathic β strand, potentially allowing TamB to chaperone nascent membrane proteins from the aqueous environment. In addition, sequence analysis suggests that the structure of TamB 963-1138 is shared by a large portion of TamB. This architecture could allow TamB to act as a conduit for membrane proteins. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Gas6/TAM System and Multiple Sclerosis.

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Bellan, Mattia; Pirisi, Mario; Sainaghi, Pier Paolo

2016-10-28

Growth arrest specific 6 (Gas6) is a multimodular circulating protein, the biological actions of which are mediated by the interaction with three transmembrane tyrosine kinase receptors: Tyro3, Axl, and MerTK, collectively named TAM. Over the last few decades, many progresses have been done in the understanding of the biological activities of this highly pleiotropic system, which plays a role in the regulation of immune response, inflammation, coagulation, cell growth, and clearance of apoptotic bodies. Recent findings have further related Gas6 and TAM receptors to neuroinflammation in general and, specifically, to multiple sclerosis (MS). In this paper, we review the biology of the Gas6/TAM system and the current evidence supporting its potential role in the pathogenesis of MS.

Clinical application and prognostic assessment of serum Tumor Associated Material (TAM) from esophageal cancer patients.

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Zhou, K; Yan, Y; Zhao, S; Li, B

2014-01-01

To explore the correlation between serum levels of Tumor Associated Materials (TAM) and clinicopathological parameters and prognosis in patients with esophageal cancer (EC). The levels of TAM were determined by chemical colorimetry in 100 EC patients and 100 healthy controls. Serum TAM levels were significantly higher in patients with esophageal carcinoma than in the control group (p TAM were associated with tumor size (p = 0.004), tumor depth (p TAM (p = 0.001). Kaplan-Meier analysis showed patients with increased levels of TAM after operation had an lower overall survival (p TAM may be an independent factor affecting the overall survival and disease-free survival (p TAM could be used to screen for tumor and assess unfavorable prognosis in patients with EC.

Estudio de la dinámica poblacional del lepidóptero Thaumetopoea pityocampa (Denis & Schiffermüller, 1775) en la provincia de Valencia.

OpenAIRE

López Sebastián, Emili

2014-01-01

Se estudió la dinámica poblacional de Thaumetopoea pityocampa (Denis & Schiffermüller, 1775) (Lepidoptera; Notodontidae) en cinco áreas de pinar ubicadas en el norte de la provincia de Valencia (España): Loma Valluenga (Rincón de Ademuz), Los Ances, La Jarilla y Las Umbrías (Los Serranos) y Pla de l’Albercoquer-Corral de Pija (Camp de Túria); la primera y última de estas masas forestales son de origen natural y regeneración espontánea, mientras que el resto son repoblaciones de origen artific...

Small molecule inhibitors block Gas6-inducible TAM activation and tumorigenicity.

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Kimani, Stanley G; Kumar, Sushil; Bansal, Nitu; Singh, Kamalendra; Kholodovych, Vladyslav; Comollo, Thomas; Peng, Youyi; Kotenko, Sergei V; Sarafianos, Stefan G; Bertino, Joseph R; Welsh, William J; Birge, Raymond B

2017-03-08

TAM receptors (Tyro-3, Axl, and Mertk) are a family of three homologous type I receptor tyrosine kinases that are implicated in several human malignancies. Overexpression of TAMs and their major ligand Growth arrest-specific factor 6 (Gas6) is associated with more aggressive staging of cancers, poorer predicted patient survival, acquired drug resistance and metastasis. Here we describe small molecule inhibitors (RU-301 and RU-302) that target the extracellular domain of Axl at the interface of the Ig-1 ectodomain of Axl and the Lg-1 of Gas6. These inhibitors effectively block Gas6-inducible Axl receptor activation with low micromolar IC 50s in cell-based reporter assays, inhibit Gas6-inducible motility in Axl-expressing cell lines, and suppress H1299 lung cancer tumor growth in a mouse xenograft NOD-SCIDγ model. Furthermore, using homology models and biochemical verifications, we show that RU301 and 302 also inhibit Gas6 inducible activation of Mertk and Tyro3 suggesting they can act as pan-TAM inhibitors that block the interface between the TAM Ig1 ectodomain and the Gas6 Lg domain. Together, these observations establish that small molecules that bind to the interface between TAM Ig1 domain and Gas6 Lg1 domain can inhibit TAM activation, and support the further development of small molecule Gas6-TAM interaction inhibitors as a novel class of cancer therapeutics.

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis.

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van der Meer, Jonathan H M; van der Poll, Tom; van 't Veer, Cornelis

2014-04-17

TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S(+/-), Gas6(-/-), TAM(-/-), and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy

NARCIS (Netherlands)

Ochodnicky, Peter; Lattenist, Lionel; Ahdi, Mohamed; Kers, Jesper; Uil, Melissa; Claessen, Nike; Leemans, Jaklien C.; Florquin, Sandrine; Meijers, Joost C. M.; Gerdes, Victor E. A.; Roelofs, Joris J. T. H.

2017-01-01

TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3,

Ligand Activation of TAM Family Receptors-Implications for Tumor Biology and Therapeutic Response.

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Davra, Viralkumar; Kimani, Stanley G; Calianese, David; Birge, Raymond B

2016-11-29

The TAM family of receptors (i.e., Tyro3, Axl, and Mertk), and their ligands Growth arrest specific factor 6 (Gas6) and Protein S (Pros1) contribute to several oncogenic processes, such as cell survival, invasion, migration, chemo-resistance, and metastasis, whereby expression often correlates with poor clinical outcomes. In recent years, there has been great interest in the study of TAM receptors in cancer, stemming both from their roles as oncogenic signaling receptors, as well as their roles in tumor immunology. As a result, several classes of TAM inhibitors that include small molecule tyrosine kinase inhibitors, monoclonal antibodies, decoy receptors, as well as novel strategies to target TAM ligands are being developed. This paper will review the biology of TAM receptors and their ligands with a focus on cancer, as well as evidence-based data for the continued pursuit of TAM/Gas6 inhibitors in clinical practice.

APLIKASI TECHNOLOGY ACCEPTANCE MODEL (TAM) PADA KOMPUTERISASI KEGIATAN PERTANAHAN

OpenAIRE

Wahyu Prabawati Putri Handayani; Mugi Harsono

2016-01-01

Abstrak: Aplikasi Technology Acceptance Model (TAM) Pada Komputerisasi Kegiatan Pertanahan. Tujuan penelitian ini adalah untuk menguji dan menganalisis pengaruh Technology Acceptance Model (TAM) Pada Komputerisasi Kegiatan Pertanahan. Sebuah metodologi survey digunakan untuk mengumpulkan data 100 karyawan. Path analysis menunjukkan bahwa (1) Computer self-efficacy berpengaruh pada persepsi kemudahan penggunaan dan persepsi manfaat teknologi, (2) Persepsi kemudahan penggunaan teknologi berpeng...

TAM receptor knockout mice are susceptible to retinal autoimmune induction.

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Ye, Fei; Li, Qiutang; Ke, Yan; Lu, Qingjun; Han, Lixia; Kaplan, Henry J; Shao, Hui; Lu, Qingxian

2011-06-16

TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU). TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology. Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina. Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.

The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites.

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Deng, Tingting; Chen, Qiaoyuan; Han, Daishu

2016-01-01

Three members of a receptor tyrosine kinase family, including Tyro3, Axl, and Mer, are collectively called as TAM receptors. TAM receptors have two common ligands, namely, growth arrest specific gene 6 (Gas6) and protein S (ProS). The TAM-Gas6/ProS system is essential for phagocytic removal of apoptotic cells, and plays critical roles in regulating immune response. Genetic studies have shown that TAM receptors are essential regulators of the tissue homeostasis in immunoprivileged sites, including the testis, retina and brain. The mechanisms by which the TAM-Gas6/ProS system regulates the tissue homeostasis in immunoprivileged sites are emerging. The roles of the TAM-Gas6/ProS system in regulating the immune privilege were intensively investigated in the mouse testis, and several studies were performed in the eye and brain. This review summarizes our current understanding of TAM signaling in the testis and other immunoprivileged tissues, as well as highlights topics that are worthy of further investigation.

TAM Receptors Are Not Required for Zika Virus Infection in Mice.

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Hastings, Andrew K; Yockey, Laura J; Jagger, Brett W; Hwang, Jesse; Uraki, Ryuta; Gaitsch, Hallie F; Parnell, Lindsay A; Cao, Bin; Mysorekar, Indira U; Rothlin, Carla V; Fikrig, Erol; Diamond, Michael S; Iwasaki, Akiko

2017-04-18

Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl -/- , Mertk -/- , Axl -/- Mertk -/- , and Axl -/- Tyro3 -/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity.

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Song, Yuguang; Liu, Yangping; Hemann, Craig; Villamena, Frederick A; Zweier, Jay L

2013-02-15

In this work, we have developed a new class of dendritic TAM radicals (TG, TdG, and dTdG) through a convergent method based on the TAM core CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type monomer. Among these radicals, dTdG exhibits the best EPR properties with sharpest EPR singlet and highest O(2) sensitivity due to deuteration of both the ester linker groups and the TAM core CT-03. Like the previous dendritic TAM radicals, these new compounds also show extremely high stability toward various reactive species owing to the dendritic encapsulation. The highly charged nature of these molecules resulting from nine carboxylate groups prevents concentration-dependent EPR line broadening at physiological pH. Furthermore, we demonstrate that these TAM radicals can be easily derivatized (e.g., PEGylation) at the nine carboxylate groups and the resulting PEGylated analogue dTdG-PEG completely inhibits the albumin binding, thereby enhancing suitability for in vivo applications. These new dendritic TAM radicals show great potential for in vivo EPR oximetric applications and provide insights on approaches to develop improved and targeted EPR oximetric probes for biomedical applications.

Functional analysis of TamA, a coactivator of nitrogen-regulated gene expression in Aspergillus nidulans.

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Small, A J; Todd, R B; Zanker, M C; Delimitrou, S; Hynes, M J; Davis, M A

2001-06-01

The tam A gene of Aspergillus nidulans encodes a 739-amino acid protein with similarity to Uga35p/Dal81p/DurLp of Saccharomyces cerevisiae. It has been proposed that TamA functions as a co-activator of AreA, the major nitrogen regulatory protein in A. nidulans. Because AreA functions as a transcriptional activator under nitrogen-limiting conditions, we investigated whether TamA was also present in the nucleus. We found that a GFP-TamA fusion protein was predominantly localised to the nucleus in the presence and absence of ammonium, and that AreA was not required for this distribution. As the predicted DNA-binding domain of TamA is not essential for function, we have used a number of approaches to further define functionally important regions. We have cloned the tamA gene of A. oryzae and compared its functional and sequence characteristics with those of A. nidulans tamA and S. cerevisiae UGA35/DAL81/DURL. The Aspergillus homologues are highly conserved and functionally interchangeable, whereas the S. cerevisiae gene does not complement a tamA mutant when expressed in A. nidulans. Uga35p/Dal81p/DurLp was also found to be unable to recruit AreA. The sequence changes in a number of tamA mutant alleles were determined, and altered versions of TamA were tested for tamA complementation and interaction with AreA. Changes in most regions of TamA appeared to destroy its function, suggesting that the overall conformation of the protein may be critical for its activity.

Cytoplasmic PELP1 and ERRgamma protect human mammary epithelial cells from Tam-induced cell death.

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Girard, Brian J; Regan Anderson, Tarah M; Welch, Siya Lem; Nicely, Julie; Seewaldt, Victoria L; Ostrander, Julie H

2015-01-01

Tamoxifen (Tam) is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+) breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1) promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples. In vitro, immortalized HMECs expressing a nuclear localization signal (NLS) mutant of PELP1 (PELP1-cyto) were resistant to Tam-induced death. Furthermore, PELP1-cyto signaling through estrogen-related receptor gamma (ERRγ) promoted cell survival in the presence of Tam. Overexpression of ERRγ in immortalized HMECs protected cells from Tam-induced death, while knockdown of ERRγ sensitized PELP1-cyto expressing HMECs to Tam. Moreover, Tam-induced HMEC cell death was independent of apoptosis and involved accumulation of the autophagy marker LC3-II. Expression of PELP1-cyto and ERRγ reduced Tam-induced LC3-II accumulation, and knockdown of ERRγ increased LC3-II levels in response to Tam. Additionally, PELP1-cyto expression led to the upregulation of MMP-3 and MAOB, known PELP1 and ERRγ target genes, respectively. Our data indicate that cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of Tam. These data suggest that PELP1 localization and/or ERRγ activation could be developed as tissue biomarkers for Tam responsiveness.

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

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Kimani, Stanley G; Kumar, Sushil; Davra, Viralkumar; Chang, Yun-Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen-I; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana S; Kotenko, Sergei V; Birge, Raymond B

2016-09-06

Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

TAM Receptors Are Not Required for Zika Virus Infection in Mice

Directory of Open Access Journals (Sweden)

Andrew K. Hastings

2017-04-01

Full Text Available Summary: Tyro3, Axl, and Mertk (TAM receptors are candidate entry receptors for infection with the Zika virus (ZIKV, an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl−/−, Mertk−/−, Axl−/−Mertk−/−, and Axl−/−Tyro3−/− mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR-blocking (MAR1-5A3 antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. : TAM receptors have been implicated as entry receptors for the Zika virus. In this study, Hastings et al. used genetic knockout mouse models to demonstrate that they are not necessary for the infection of mice via multiple routes of viral challenge. These results suggest the existence of redundant entry receptors for ZIKV in mice. Keywords: viral entry, flavivirus, neurotropic virus, CNS, pregnancy, congenital infection

Targeting Gas6/TAM in cancer cells and tumor microenvironment.

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Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

2018-01-31

Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

TAM receptors support neural stem cell survival, proliferation and neuronal differentiation.

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Ji, Rui; Meng, Lingbin; Jiang, Xin; Cvm, Naresh Kumar; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2014-01-01

Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III+) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.

Increased Circulating and Urinary Levels of Soluble TAM Receptors in Diabetic Nephropathy.

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Ochodnicky, Peter; Lattenist, Lionel; Ahdi, Mohamed; Kers, Jesper; Uil, Melissa; Claessen, Nike; Leemans, Jaklien C; Florquin, Sandrine; Meijers, Joost C M; Gerdes, Victor E A; Roelofs, Joris J T H

2017-09-01

TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion 300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors.

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Bhattacharyya, Suchita; Zagórska, Anna; Lew, Erin D; Shrestha, Bimmi; Rothlin, Carla V; Naughton, John; Diamond, Michael S; Lemke, Greg; Young, John A T

2013-08-14

Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. Copyright © 2013 Elsevier Inc. All rights reserved.

Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

Science.gov (United States)

Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

2017-06-01

Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

Technology Acceptance Model (TAM) untuk Menganalisis Penerimaan terhadap Sistem Informasi di PerpustakaanM INFORMASI PERPUSTAKAAN

OpenAIRE

Fatmawati, Endang

2015-01-01

Technology acceptance can be defined as a user's willingness to employ technology for the tasks it is designed to support. Technology Acceptance Model (TAM) introduced by Davis in 1986. TAM is considers user perceptions of ease of use and usefulness as the main factors affecting the acceptance level of any technology. TAM is model for explaining and predicting information system use in library. TAM model to determine the attitude of users towards a technology acceptance.

The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.

Science.gov (United States)

Shafit-Zagardo, Bridget; Gruber, Ross C; DuBois, Juwen C

2018-03-04

Tyro3, Axl, and Mertk, referred to as the TAM family of receptor tyrosine kinases, are instrumental in maintaining cell survival and homeostasis in mammals. TAM receptors interact with multiple signaling molecules to regulate cell migration, survival, phagocytosis and clearance of metabolic products and cell debris called efferocytosis. The TAMs also function as rheostats to reduce the expression of proinflammatory molecules and prevent autoimmunity. All three TAM receptors are activated in a concentration-dependent manner by the vitamin K-dependent growth arrest-specific protein 6 (Gas6). Gas6 and the TAMs are abundantly expressed in the nervous system. Gas6, secreted by neurons and endothelial cells, is the sole ligand for Axl. ProteinS1 (ProS1), another vitamin K-dependent protein functions mainly as an anti-coagulant, and independent of this function can activate Tyro3 and Mertk, but not Axl. This review will focus on the role of the TAM receptors and their ligands in the nervous system. We highlight studies that explore the function of TAM signaling in myelination, the visual cortex, neural cancers, and multiple sclerosis (MS) using Gas6 -/- and TAM mutant mice models. Copyright © 2018. Published by Elsevier Inc.

Subcellular compartmentalization of Cd and Zn in two bivalves. II. Significance of trophically available metal (TAM)

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Wallace, W.G.; Luoma, S.N.

2003-01-01

This paper examines how the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis may affect the trophic transfer of metal to predators. Results show that the partitioning of metals to organelles, 'enzymes' and metallothioneins (MT) comprise a subcellular compartment containing trophically available metal (TAM; i.e. metal trophically available to predators), and that because this partitioning varies with species, animal size and metal, TAM is similarly influenced. Clams from San Francisco Bay, California, were exposed for 14 d to 3.5 ??g 1-1 Cd and 20.5 ??g 1-1 Zn, including 109Cd and 65Zn as radiotracers, and were used in feeding experiments with grass shrimp Palaemon macrodatylus, or used to investigate the subcellular partitioning of metal. Grass shrimp fed Cd-contaminated P. amurensis absorbed ???60% of ingested Cd, which was in accordance with the partitioning of Cd to the bivalve's TAM compartment (i.e. Cd associated with organelles, 'enzymes' and MT); a similar relationship was found in previous studies with grass shrimp fed Cd-contaminated oligochaetes. Thus, TAM may be used as a tool to predict the trophic transfer of at least Cd. Subcellular fractionation revealed that ???34% of both the Cd and Zn accumulated by M. balthica was associated with TAM, while partitioning to TAM in P. amurensis was metal-dependent (???60% for TAM-Cd%, ???73% for TAM-Zn%). The greater TAM-Cd% of P. amurensis than M. balthica is due to preferential binding of Cd to MT and 'enzymes', while enhanced TAM-Zn% of P. amurensis results from a greater binding of Zn to organelles. TAM for most species-metal combinations was size-dependent, decreasing with increased clam size. Based on field data, it is estimated that of the 2 bivalves, P. amurensis poses the greater threat of Cd exposure to predators because of higher tissue concentrations and greater partitioning as TAM; exposure of Zn to predators would be similar between these species.

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.

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Paolino, Magdalena; Penninger, Josef M

2016-10-21

The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

Kajian Online Sistem Informasi BRI (BRINETS: Pendekatan Technology Acceptance Model (TAM

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Wahyu Meiranto

2011-04-01

Full Text Available Study of BRI Online Information System (BRINETS: Technology Acceptance Model (TAM Approach. The purpose of this research is to analyze factors that effecting acceptance and actual use of BRI technology information system (BRINETS using TAM (Technology Acceptance Model. Two variables of TAM used in this research are perceived ease of use and perceived of usefullness. Samples of the research were BRINETS users at BRI Semarang. There were 70 respondents involved. The data was analyzed by using PLS. The results indicate that experience and complexity have significant effect to perceived ease of use. Furthermore, perceived ease of use significantly affected the attitude toward using technology. Finally, behaviour intention significantly influence the actual use of technology

Influencia de la selecci??n de planta hospedadora, de los parasitoides y de la competencia intraespec??fica en el desarrollo y mortalidad de la procesionaria del pino (Thaumetopoea pityocampa)

OpenAIRE

P??rez-Contreras, Tom??s

2004-01-01

Se han estudiado diversos aspectos de la ecol??gia de la procesionaria del pino (Thaumetopoea pityocampa), un lepid??ptero heter??cero, de la familia Thaumetopoidaes, que constituye la principal plaga defoliadora de distintas especies de pino en el ??rea mediterranea. El trabajo de campo se realiz?? durante el per??odo 1993-1996, en un pinar de repoblaci??n compuesto por pino de Alepo (pinus halepensis) y pino mar??timo (pinus pinaster), localizado al este de la provincia de Granada. Debido a...

IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

Science.gov (United States)

Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

2015-06-01

About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.

Molecular insights of Gas6/TAM in cancer development and therapy.

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Wu, Guiling; Ma, Zhiqiang; Hu, Wei; Wang, Dongjin; Gong, Bing; Fan, Chongxi; Jiang, Shuai; Li, Tian; Gao, Jianyuan; Yang, Yang

2017-03-23

Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML. Interestingly, Gas6 also has a role in establishing tumour dormancy in the bone marrow microenvironment and in suppressing intestinal tumorigenesis. Numerous studies regarding cancer therapy have targeted Gas6 and TAM receptors with good results. However, some findings have suggested that Gas6 is associated with the development of resistance to cancer therapies. Concerning these significant effects of Gas6 in numerous cancers, we discuss the roles of Gas6 in cancer development in this review. First, we introduce basic knowledge on Gas6 and TAM receptors. Next, we describe and discuss the involvement of Gas6 and TAM receptors in cancers from different organ systems. Finally, we highlight the progress in therapies targeting Gas6 and TAM receptors. This review presents the significant roles of Gas6 in cancers from different systems and may contribute to the continued promotion of Gas6 as a therapeutic target.

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

NARCIS (Netherlands)

van der Meer, Jonathan H. M.; van der Poll, Tom; van 't Veer, Cornelis

2014-01-01

TAM receptors (Tyro3, Axl, andMer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein

Modeling the acceptance of clinical information systems among hospital medical staff: an extended TAM model.

Science.gov (United States)

Melas, Christos D; Zampetakis, Leonidas A; Dimopoulou, Anastasia; Moustakis, Vassilis

2011-08-01

Recent empirical research has utilized the Technology Acceptance Model (TAM) to advance the understanding of doctors' and nurses' technology acceptance in the workplace. However, the majority of the reported studies are either qualitative in nature or use small convenience samples of medical staff. Additionally, in very few studies moderators are either used or assessed despite their importance in TAM based research. The present study focuses on the application of TAM in order to explain the intention to use clinical information systems, in a random sample of 604 medical staff (534 physicians) working in 14 hospitals in Greece. We introduce physicians' specialty as a moderator in TAM and test medical staff's information and communication technology (ICT) knowledge and ICT feature demands, as external variables. The results show that TAM predicts a substantial proportion of the intention to use clinical information systems. Findings make a contribution to the literature by replicating, explaining and advancing the TAM, whereas theory is benefited by the addition of external variables and medical specialty as a moderator. Recommendations for further research are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of Test-Analysis Models (TAM) for correlation of dynamic test and analysis results

Science.gov (United States)

Angelucci, Filippo; Javeed, Mehzad; Mcgowan, Paul

1992-01-01

The primary objective of structural analysis of aerospace applications is to obtain a verified finite element model (FEM). The verified FEM can be used for loads analysis, evaluate structural modifications, or design control systems. Verification of the FEM is generally obtained as the result of correlating test and FEM models. A test analysis model (TAM) is very useful in the correlation process. A TAM is essentially a FEM reduced to the size of the test model, which attempts to preserve the dynamic characteristics of the original FEM in the analysis range of interest. Numerous methods for generating TAMs have been developed in the literature. The major emphasis of this paper is a description of the procedures necessary for creation of the TAM and the correlation of the reduced models with the FEM or the test results. Herein, three methods are discussed, namely Guyan, Improved Reduced System (IRS), and Hybrid. Also included are the procedures for performing these analyses using MSC/NASTRAN. Finally, application of the TAM process is demonstrated with an experimental test configuration of a ten bay cantilevered truss structure.

Explaining the Discrepancy in the Mediating Role of Attitude in the TAM

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López-Bonilla, Luis Miguel; López-Bonilla, Jesús Manuel

2017-01-01

The debate about the role of attitude in the technology acceptance model (TAM) seems to have re-emerged in two prestigious journals in the field of educational technology. Among the publications on this debate, there are authors in favour of excluding the attitude of TAM, whereas others are in favour of including it. These opinions are derived…

TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

Science.gov (United States)

Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2013-12-15

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

Online Marketing Enterprise of Jombang Culinary from TAM and VEM Perspective on Social Media

Directory of Open Access Journals (Sweden)

nuri purwanto

2017-11-01

Full Text Available The purpose of this research was to develop, evaluate, and test antecedent model with trust as an intermediary variable of Technology Acceptances Model (TAM and Virtual Experiential Marketing (VEM for buying intention. It used purposive sampling technique with 300 respondents. The questionnaire results were evaluated and analyzed using Structural Equation Model (SEM method with the analysis tools (the third version of SmartPLS. The research result shows that there is no effect between TAM and trust. In addition, there is a direct and positive influence of VEM on trust. The trust and TAM have a positive effect on buying intention. However, VEM does not affect buying intention. The results indicate that the trust cannot mediate TAM and buying intention. Meanwhile, trust can mediate between VEM and buying intention.

The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

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Miner, Jonathan J; Daniels, Brian P; Shrestha, Bimmi; Proenca-Modena, Jose L; Lew, Erin D; Lazear, Helen M; Gorman, Matthew J; Lemke, Greg; Klein, Robyn S; Diamond, Michael S

2015-12-01

The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and downregulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl, but not Tyro3, exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse encephalitis viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with interferon-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development.

Utilization of Multimedia Laboratory: An Acceptance Analysis using TAM

Science.gov (United States)

Modeong, M.; Palilingan, V. R.

2018-02-01

Multimedia is often utilized by teachers to present a learning materials. Learning that delivered by multimedia enables people to understand the information of up to 60% of the learning in general. To applying the creative learning to the classroom, multimedia presentation needs a laboratory as a space that provides multimedia needs. This study aims to reveal the level of student acceptance on the multimedia laboratories, by explaining the direct and indirect effect of internal support and technology infrastructure. Technology Acceptance Model (TAM) is used as the basis of measurement on this research, through the perception of usefulness, ease of use, and the intention, it’s recognized capable of predicting user acceptance about technology. This study used the quantitative method. The data analysis using path analysis that focuses on trimming models, it’s performed to improve the model of path analysis structure by removing exogenous variables that have insignificant path coefficients. The result stated that Internal Support and Technology Infrastructure are well mediated by TAM variables to measure the level of technology acceptance. The implications suggest that TAM can measure the success of multimedia laboratory utilization in Faculty of Engineering UNIMA.

Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome.

Science.gov (United States)

Saida, Satoshi; Watanabe, Ken-ichiro; Sato-Otsubo, Aiko; Terui, Kiminori; Yoshida, Kenichi; Okuno, Yusuke; Toki, Tsutomu; Wang, RuNan; Shiraishi, Yuichi; Miyano, Satoru; Kato, Itaru; Morishima, Tatsuya; Fujino, Hisanori; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Adachi, Souichi; Ito, Etsuro; Ogawa, Seishi; Ito, Mamoru; Nakahata, Tatsutoshi; Heike, Toshio

2013-05-23

Transient abnormal myelopoiesis (TAM) is a clonal preleukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism of leukemogenesis in this disorder, a xenograft model of TAM was established using NOD/Shi-scid, interleukin (IL)-2Rγ(null) mice. Serial engraftment after transplantation of cells from a TAM patient who developed ML-DS a year later demonstrated their self-renewal capacity. A GATA1 mutation and no copy number alterations (CNAs) were detected in the primary patient sample by conventional genomic sequencing and CNA profiling. However, in serial transplantations, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, which are clinically associated with ML-DS. Detailed genomic analysis identified minor subclones with a 16q deletion or this distinct GATA1 mutation in the primary patient sample. These results suggest that genetically heterogeneous subclones with varying leukemia-initiating potential already exist in the neonatal TAM phase, and ML-DS may develop from a pool of such minor clones through clonal selection. Our xenograft model of TAM may provide unique insight into the evolutionary process of leukemia.

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.

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Espindola, Milena S; Habiel, David M; Narayanan, Rohan; Jones, Isabelle; Coelho, Ana L; Murray, Lynne A; Jiang, Dianhua; Noble, Paul W; Hogaboam, Cory M

2018-06-01

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling, which progressively abolishes lung function in an RTK (receptor tyrosine kinase)-dependent manner. Gas6 (growth arrest-specific 6) ligand, Tyro3 (TYRO3 protein tyrosine kinase 3), and Axl (anexelekto) RTK expression and activity are increased in IPF. To determine if targeting these RTK pathways would inhibit fibroblast activation and the development of pulmonary fibrosis. Quantitative genomic, proteomic, and functional analyses were used to determine Gas6/TAM (Tyro3, Axl, and Mertk [MER proto-oncogene, tyrosine kinase]) RTK expression and activation in tissues and fibroblasts from normal and IPF lungs. The profibrotic impact of these RTK pathways were also examined in bleomycin-induced pulmonary fibrosis and in SCID/Bg mice that developed pulmonary fibrosis after the intravenous administration of primary IPF fibroblasts. Gas6, Axl, and Tyro3 were increased in both rapidly and slowly progressive IPF compared with normal lung samples and fibroblasts. Targeting these pathways with either specific antibodies directed at Gas6 or Axl, or with small-molecule TAM inhibitors indicated that the small molecule-mediated targeting approach was more efficacious in both in vitro and in vivo studies. Specifically, the TAM receptor inhibitor R428 (also known as BGB324) significantly inhibited the synthetic, migratory, and proliferative properties of IPF fibroblasts compared with the other Gas6/TAM receptor targeting agents. Finally, loss of Gas6 expression decreased lung fibrotic responses to bleomycin and treatment with R428 inhibited pulmonary fibrosis in humanized SCID/Bg mice. Gas6/TAM receptor activity contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK pathway might be an effective antifibrotic strategy in this disease.

Understanding Student Teachers’ Behavioural Intention to Use Technology: Technology Acceptance Model (TAM Validation and Testing

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Kung-Teck, Wong

2013-01-01

Full Text Available This study sets out to validate and test the Technology Acceptance Model (TAM in the context of Malaysian student teachers’ integration of their technology in teaching and learning. To establish factorial validity, data collected from 302 respondents were tested against the TAM using confirmatory factor analysis (CFA, and structural equation modelling (SEM was used for model comparison and hypotheses testing. The goodness-of-fit test of the analysis shows partial support of the applicability of the TAM in a Malaysian context. Overall, the TAM accounted for 37.3% of the variance in intention to use technology among student teachers and of the five hypotheses formulated, four are supported. Perceived usefulness is a significant influence on attitude towards computer use and behavioural intention. Perceived ease of use significantly influences perceived usefulness, and finally, behavioural intention is found to be influenced by attitude towards computer use. The findings of this research contribute to the literature by validating the TAM in the Malaysian context and provide several prominent implications for the research and practice of technology integration development.

MODEL PERILAKU PENGGUNAAN TIK “NR2007” PENGEMBANGAN DARI TECHNOLOGY ACCEPTANCE MODEL (TAM

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Neila Ramdhani

2016-06-01

Full Text Available This paper discusses and criticizes a Technology Acceptance Model which was developed by Fred D. Davis in 1986. TAM was built to predict the way people accept and adopt the technology. TAM was inspired by theory of reasoned action (TRA formulated by Martin Fishbein & Icek Ajzen in 1975, although the model does not completely adopt the TRA model. TAM does not include Subjective Norm as a factor in predicting the use of technology. As a theory, TAM has been used by many researchers to investigate the adoption of information technology. This model has a significant contribution in predicting the use of information communication technology (ICT in many areas. Since ICT users have various motivational backgrounds, some of them have a positive attitude toward ICT, but they do not use ICT. It seems the TAM model need to be improved by including Subjective Norms and Perceived Behavior Control as suggested by Ajzen in the theory of planned behavior (TPB as antecedents of intention to use ICT. Since the personality background of ICT users may also influence the use of ICT, the author proposes TAM‐NR‐2007 model that include personality traits as a background factor of attitude toward the behavior and subjective norms.

Influencia de la selección de planta hospedadora, de los parasitoides y de la competencia intraespecífica en el desarrollo y mortalidad de la procesionaria del pino (Thaumetopoea pityocampa)

OpenAIRE

Pérez-Contreras, Tomás

2013-01-01

Se han estudiado diversos aspectos de la ecológia de la procesionaria del pino (Thaumetopoea pityocampa), un lepidóptero heterócero, de la familia Thaumetopoidaes, que constituye la principal plaga defoliadora de distintas especies de pino en el área mediterranea. El trabajo de campo se realizó durante el período 1993-1996, en un pinar de repoblación compuesto por pino de Alepo (pinus halepensis) y pino marítimo (pinus pinaster), localizado al este de la provincia de Granada. Debido a las dif...

The bromodomain protein LEX-1 acts with TAM-1 to modulate gene expression in C. elegans.

Science.gov (United States)

Tseng, Rong-Jeng; Armstrong, Kristin R; Wang, Xiaodong; Chamberlin, Helen M

2007-11-01

In many organisms, repetitive DNA serves as a trigger for gene silencing. However, some gene expression is observed from repetitive genomic regions such as heterochromatin, suggesting mechanisms exist to modulate the silencing effects. From a genetic screen in C. elegans, we have identified mutations in two genes important for expression of repetitive sequences: lex-1 and tam-1. Here we show that lex-1 encodes a protein containing an ATPase domain and a bromodomain. LEX-1 is similar to the yeast Yta7 protein, which maintains boundaries between silenced and active chromatin. tam-1 has previously been shown to encode a RING finger/B-box protein that modulates gene expression from repetitive DNA. We find that lex-1, like tam-1, acts as a class B synthetic multivulva (synMuv) gene. However, since lex-1 and tam-1 mutants have normal P granule localization, it suggests they act through a mechanism distinct from other class B synMuvs. We observe intragenic (interallelic) complementation with lex-1 and a genetic interaction between lex-1 and tam-1, data consistent with the idea that the gene products function in the same biological process, perhaps as part of a protein complex. We propose that LEX-1 and TAM-1 function together to influence chromatin structure and to promote expression from repetitive sequences.

Application of the Technology Acceptance Model (TAM) in electronic ...

African Journals Online (AJOL)

Application of the Technology Acceptance Model (TAM) in electronic ticket purchase for ... current study examined the perceived usefulness and ease of use of online technology ... The findings are discussed in the light of these perspectives.

TAM: a method for enrichment and depletion analysis of a microRNA category in a list of microRNAs.

Science.gov (United States)

Lu, Ming; Shi, Bing; Wang, Juan; Cao, Qun; Cui, Qinghua

2010-08-09

MicroRNAs (miRNAs) are a class of important gene regulators. The number of identified miRNAs has been increasing dramatically in recent years. An emerging major challenge is the interpretation of the genome-scale miRNA datasets, including those derived from microarray and deep-sequencing. It is interesting and important to know the common rules or patterns behind a list of miRNAs, (i.e. the deregulated miRNAs resulted from an experiment of miRNA microarray or deep-sequencing). For the above purpose, this study presents a method and develops a tool (TAM) for annotations of meaningful human miRNAs categories. We first integrated miRNAs into various meaningful categories according to prior knowledge, such as miRNA family, miRNA cluster, miRNA function, miRNA associated diseases, and tissue specificity. Using TAM, given lists of miRNAs can be rapidly annotated and summarized according to the integrated miRNA categorical data. Moreover, given a list of miRNAs, TAM can be used to predict novel related miRNAs. Finally, we confirmed the usefulness and reliability of TAM by applying it to deregulated miRNAs in acute myocardial infarction (AMI) from two independent experiments. TAM can efficiently identify meaningful categories for given miRNAs. In addition, TAM can be used to identify novel miRNA biomarkers. TAM tool, source codes, and miRNA category data are freely available at http://cmbi.bjmu.edu.cn/tam.

An interview with Patrick Tam by Kathryn Senior.

Science.gov (United States)

Tam, Patrick

2010-12-01

Patrick Tam's research is focused on the cellular and molecular mechanisms of body patterning during mouse development. He agreed to be interviewed by Development to talk about his interest in mouse development, new concepts in gastrulation, X-linked diseases and his dream of an African safari.

Understanding Student Teachers' Behavioural Intention to Use Technology: Technology Acceptance Model (TAM) Validation and Testing

Science.gov (United States)

Wong, Kung-Teck; Osman, Rosma bt; Goh, Pauline Swee Choo; Rahmat, Mohd Khairezan

2013-01-01

This study sets out to validate and test the Technology Acceptance Model (TAM) in the context of Malaysian student teachers' integration of their technology in teaching and learning. To establish factorial validity, data collected from 302 respondents were tested against the TAM using confirmatory factor analysis (CFA), and structural equation…

Growth Arrest-Specific 6 (Gas6) and TAM Receptors in Mouse Platelets.

Science.gov (United States)

Uras, Fikriye; Küçük, Burhanettin; Bingöl Özakpınar, Özlem; Demir, Ahmet Muzaffer

2015-03-05

Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not. Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens. RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method. We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.

TAM receptor tyrosine kinase function and the immunopathology of liver disease.

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Mukherjee, S K; Wilhelm, A; Antoniades, C G

2016-06-01

Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology. Copyright © 2016 the American Physiological Society.

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

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Paolino, Magdalena; Choidas, Axel; Wallner, Stephanie; Pranjic, Blanka; Uribesalgo, Iris; Loeser, Stefanie; Jamieson, Amanda M; Langdon, Wallace Y; Ikeda, Fumiyo; Fededa, Juan Pablo; Cronin, Shane J; Nitsch, Roberto; Schultz-Fademrecht, Carsten; Eickhoff, Jan; Menninger, Sascha; Unger, Anke; Torka, Robert; Gruber, Thomas; Hinterleitner, Reinhard; Baier, Gottfried; Wolf, Dominik; Ullrich, Axel; Klebl, Bert M; Penninger, Josef M

2014-03-27

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.

MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression.

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Jiang, Hua; Cheng, Lin; Hu, Pan; Liu, Renbin

2018-05-23

Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown. Therefore, the aim of the present study was to investigate the role of miRNA‑663b in TAM resistance in breast cancer. The results demonstrated that miRNA‑663b was upregulated in breast cancer with TAM resistance. Tumor protein 73 (TP73) was a direct target of miRNA‑663b, and was negatively regulated by miRNA‑663b in MCF‑7 cells. Furthermore, it was identified that downregulation of miRNA‑663b inhibited cell proliferation ability and promoted cell apoptosis, resulting in enhanced TAM sensitivity. In addition, these findings suggested that TP73 silencing may have eliminated the effects of miRNA‑663b inhibitor on breast cancer cells. In conclusion, the present study verified a novel molecular link between miRNA‑663b and TP73, and indicated that miRNA‑663b may be a critical therapeutic target in breast cancer.

Genetic diversity and phylogenetic analysis of Tams1 of Theileria annulata isolates from three continents between 2000 and 2012.

Science.gov (United States)

Wang, Jiay; Yang, Xianyong; Wang, Yuge; Jing, Zhihong; Meng, Kai; Liu, Jianzhu; Guo, Huijun; Xu, Ruixue; Cheng, Ziqiang

2014-01-01

Theileria annulata, which is part of the Theileria sergenti/Theileria buffeli/Theileria orientalis group, preferentially infects cattle and results in high mortality and morbidity in the Mediterranean, Middle East, and Central Asia. The polypeptide Tams1 is an immunodominant major merozoite piroplasm surface antigen of T. annulata that could be used as a marker for epidemiological studies and phylogenetic analysis. In the present study, a total of 155 Tams1 sequences were investigated for genetic diversity and phylogenetic relationships through phylogenetic analysis. Results showed that the Tams1 sequences were divided into two major groups and that distribution for some isolates also exhibited geographic specificity. As targeting polymorphic genes for parasite detection may result in underestimation of infection, polymerase chain reaction (PCR) assay using two different probes targeting tams-1 genes of these two groups can be more credible. In addition, the direction of the spread of the disease was discovered to be from the Mediterranean or the tropical zone to the Eurasian peninsula, Middle East, Southern Asia, and Africa, particularly for Group 2. A similar occurrence was also found between the Ms1 gene of Theileria lestoquardi and the Tams1 gene of T. annulata, which explains cross-immunogenicity to a certain extent. However, no potential glycosylation site in the Tams1 of T. annulata was found in this study, which illustrated that instead of N-glycosylation, other modifications have more significant effects on the immunogenicity of the Tams1 protein.

The lack of cross-national equivalence of a therapist adherence measure (TAM-R) in multisystemic therapy (MST)

NARCIS (Netherlands)

Lange, A.M.C.; Scholte, R.H.J.; Geffen, W. van; Timman, R.; Busschbach, J.J.V. van; Rijken, R.E.A. van der

2016-01-01

This two-study report investigates the equivalence of the Dutch Therapist Adherence Measure Revised (TAM-R) to the US original. The TAM-R is a questionnaire measuring therapist adherence to the treatment model of Multisystemic Therapy (MST). Monitoring of therapist adherence is essential for

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

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Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

Science.gov (United States)

Lee, Iris J; Hilliard, Brendan A; Ulas, Mehriban; Yu, Daohai; Vangala, Chandan; Rao, Swati; Lee, Jean; Gadegbeku, Crystal A; Cohen, Philip L

2015-06-01

Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation. The receptors exist in both soluble and cell-bound forms; the soluble receptors (sAxl and sMer) are believed to compete with the bound receptors and thus inhibit their function. In this study, we determined the expression of cell-bound and soluble TAM proteins in patients with CKD. CKD patients had significantly lower expression of Mer in monocytes, yet increased expression of soluble TAM receptors sAxl and sMer in plasma compared to controls. The metalloproteinase ADAM 17, responsible for cleavage of Mer to its soluble form, was increased in patient monocytes. Elevated levels of soluble TAM receptors were more evident in patients with progressive renal failure. These observations suggest that functional deficiency of TAM receptor-mediated regulation of inflammation may contribute to chronic inflammation in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

TAM AIRLINES ON TWITTER: COMMUNICATION CHANNEL OR SOCIAL NETWORK?

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Cynthia Harumy Watanabe Corrêa

2010-12-01

Full Text Available The research emphasizes the social appropriation of Information and Communication Technologies by the Brazilian aviation industry, through a case study of communication strategies of TAM on the social networking site Twitter. TAM is a leader in the Brazilian domestic market and gradually conquering its space in Mercosul. This is an exploratory research, based on content analysis of messages sent to the company profile on Twitter, in order to check whether indeed the consolidation of a social network between TAM and its followers. We analyzed all messages posted since July 3, 2009, the date of the first post in the company profile, until the day January 31, 2010. Among the subjects discussed, there was the predominance of information and promotions. The study concludes that, under Twitter, TAM has yet reached a high degree of social interaction with his followers, because the major number of messages is directed to promotional marketing.

[Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

Science.gov (United States)

Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

2012-09-01

To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (PTAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (PTAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

Tyura Tam Space Launch Facility, Kazakhstan, CIS

Science.gov (United States)

1992-01-01

Located in Kazakhstan on the Syr Darya River, the Tyura Tam Cosmodrome has been the launch site for 72 cosmonaut crews. The landing runway of the Buran space shuttle can be seen in the left center. Further to the right, near the center is the launch site for the Soyuz. The mission control center is located 1,300 miles away near Moscow. In the lower right, is the city of Leninsk, seen as a dark region next to the river.

Dynamic Simulation of 1D Cellular Automata in the Active aTAM.

Science.gov (United States)

Jonoska, Nataša; Karpenko, Daria; Seki, Shinnosuke

2015-07-01

The Active aTAM is a tile based model for self-assembly where tiles are able to transfer signals and change identities according to the signals received. We extend Active aTAM to include deactivation signals and thereby allow detachment of tiles. We show that the model allows a dynamic simulation of cellular automata with assemblies that do not record the entire computational history but only the current updates of the states, and thus provide a way for (a) algorithmic dynamical structural changes in the assembly and (b) reusable space in self-assembly. The simulation is such that at a given location the sequence of tiles that attach and detach corresponds precisely to the sequence of states the synchronous cellular automaton generates at that location.

The relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma.

Science.gov (United States)

Chen, G

2017-02-01

To explore the relationship between the expression of TAM, survivin and the degree of necrosis of the tumor after cisplatin treatment in osteosarcoma. The mice model of osteosarcoma S180 were injected with 6 mg/kg/day of cisplatin (observation group) or the same amount of normal saline (control group) for 4 weeks. Mice were sacrificed at days 1, 4, 9, 14, 18, 22 and 28, respectively, 24 h before administration of the drug or saline, and tumor tissues were collected. The size of the tumor samples was measured and the correlation of TAM, survivin expression in osteosarcoma and necrosis degree of tumor tissue after cisplatin treatment was studied using various methods including fluorescence quantitative PCR, enzyme linked immunosorbent assay (ELISA), Western blotting and immunohistochemistry. Fluorescence quantitative PCR showed that the expression of TAM, survivin mRNA in the control group was significantly higher than that in the observation group. Also, the ELISA monitoring showed that the expression of mice TAM, survivin protein in vivo was significantly lower than TAM, survivin protein expression of mice in vivo in the observation group (2.3 µg/l, 1.6 µg/l) relatively to the control group (9.7 mg/l, 10.3 µg/l). Consistent with the Western blot data, ELISA results showed that the expression of survivin and TAM protein decreased gradually with the prolongation of drug treatment along the time in the observation group. The volume and weight of the tumor in the observation group were significantly less than that of the control group. Additionally, the tumor necrosis of mice in the observation group was more significant, suggesting that the meant of the size of tumor tissue decreased significantly with the extension of the time of drug treatment. Immunohistochemical results showed that the rate of the positive cell of TAM and survivin in the observation group (82.3%) was significantly higher (pTAM gradually declined at the level of the trend with the extension of

The Axl kinase domain in complex with a macrocyclic inhibitor offers first structural insights into an active TAM receptor kinase.

Science.gov (United States)

Gajiwala, Ketan S; Grodsky, Neil; Bolaños, Ben; Feng, Junli; Ferre, RoseAnn; Timofeevski, Sergei; Xu, Meirong; Murray, Brion W; Johnson, Ted W; Stewart, Al

2017-09-22

The receptor tyrosine kinase family consisting of Tyro3, Axl, and Mer (TAM) is one of the most recently identified receptor tyrosine kinase families. TAM receptors are up-regulated postnatally and maintained at high levels in adults. They all play an important role in immunity, but Axl has also been implicated in cancer and therefore is a target in the discovery and development of novel therapeutics. However, of the three members of the TAM family, the Axl kinase domain is the only one that has so far eluded structure determination. To this end, using differential scanning fluorimetry and hydrogen-deuterium exchange mass spectrometry, we show here that a lower stability and greater dynamic nature of the Axl kinase domain may account for its poor crystallizability. We present the first structural characterization of the Axl kinase domain in complex with a small-molecule macrocyclic inhibitor. The Axl crystal structure revealed two distinct conformational states of the enzyme, providing a first glimpse of what an active TAM receptor kinase may look like and suggesting a potential role for the juxtamembrane region in enzyme activity. We noted that the ATP/inhibitor-binding sites of the TAM members closely resemble each other, posing a challenge for the design of a selective inhibitor. We propose that the differences in the conformational dynamics among the TAM family members could potentially be exploited to achieve inhibitor selectivity for targeted receptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

TAM-based external factors related to ERP solutions acceptance in organizations

Directory of Open Access Journals (Sweden)

Simona Zabukovsek

2013-01-01

Full Text Available To improve the efficiency and effectiveness of ERP solutions use, understanding of critical success factors of ERP solutions assimilation in organizations is crucial. The technology acceptance model (TAM proposed by Davis (1989 has been the most widely used model for researching user acceptance and usage of IT/IS. The purpose of this paper is to extend the original TAM with groups of external factors which impact actual ERP system use. First, we focus on ERP system use in companies’ maturity phase. Second, we expose and examine three groups of external factors which influence ERP usage. The model was empirically tested using data collected from a survey of ERP users in 44 organizations. Survey data have been collected from ERP users who have been exposed to an ERP system which has operated for more than one year. The proposed research model was analyzed using the PLS approach.

The Tyrosine Aminomutase TAM1 Is Required for β-Tyrosine Biosynthesis in Rice

Science.gov (United States)

Yan, Jian; Aboshi, Takako; Teraishi, Masayoshi; Strickler, Susan R.; Spindel, Jennifer E.; Tung, Chih-Wei; Takata, Ryo; Matsumoto, Fuka; Maesaka, Yoshihiro; McCouch, Susan R.; Okumoto, Yutaka; Mori, Naoki; Jander, Georg

2015-01-01

Non-protein amino acids, often isomers of the standard 20 protein amino acids, have defense-related functions in many plant species. A targeted search for jasmonate-induced metabolites in cultivated rice (Oryza sativa) identified (R)-β-tyrosine, an isomer of the common amino acid (S)-α-tyrosine in the seeds, leaves, roots, and root exudates of the Nipponbare cultivar. Assays with 119 diverse cultivars showed a distinct presence/absence polymorphism, with β-tyrosine being most prevalent in temperate japonica cultivars. Genetic mapping identified a candidate gene on chromosome 12, which was confirmed to encode a tyrosine aminomutase (TAM1) by transient expression in Nicotiana benthamiana and in vitro enzyme assays. A point mutation in TAM1 eliminated β-tyrosine production in Nipponbare. Rice cultivars that do not produce β-tyrosine have a chromosome 12 deletion that encompasses TAM1. Although β-tyrosine accumulation was induced by the plant defense signaling molecule jasmonic acid, bioassays with hemipteran and lepidopteran herbivores showed no negative effects at physiologically relevant β-tyrosine concentrations. In contrast, root growth of Arabidopsis thaliana and other tested dicot plants was inhibited by concentrations as low as 1 μM. As β-tyrosine is exuded into hydroponic medium at higher concentrations, it may contribute to the allelopathic potential of rice. PMID:25901084

TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy.

Science.gov (United States)

Akalu, Yemsratch T; Rothlin, Carla V; Ghosh, Sourav

2017-03-01

Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

State-of-the-art of small molecule inhibitors of the TAM family: the point of view of the chemist.

Science.gov (United States)

Baladi, Tom; Abet, Valentina; Piguel, Sandrine

2015-11-13

The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure-activity relationships, drug-metabolism and pharmacokinetics properties where they exist. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes.

Science.gov (United States)

Wang, Xiaomei; Malawista, Anna; Qian, Feng; Ramsey, Christine; Allore, Heather G; Montgomery, Ruth R

2018-02-09

The multifactorial immune deterioration in aging--termed "inflamm-aging"--is comprised of a state of low-grade, chronic inflammation and complex dysregulation of responses to immune stimulation. The TAM family (Tyro 3, Axl, and Mer) of receptor tyrosine kinases are negative regulators of Toll like receptor-mediated immune responses that broadly inhibit cytokine receptor cascades to inhibit inflammation. Here we demonstrate elevated expression of TAM receptors in monocytes of older adults, and an age-dependent difference in signaling mediator AKT resulting in dysregulated responses to signaling though Mer. Our results may be especially significant in tissue, where levels of Mer are highest, and may present avenues for modulation of chronic tissue inflammation noted in aging.

Porphyromonas gingivalis Promotes Unrestrained Type I Interferon Production by Dysregulating TAM Signaling via MYD88 Degradation.

Science.gov (United States)

Mizraji, Gabriel; Nassar, Maria; Segev, Hadas; Sharawi, Hafiz; Eli-Berchoer, Luba; Capucha, Tal; Nir, Tsipora; Tabib, Yaara; Maimon, Avraham; Dishon, Shira; Shapira, Lior; Nussbaum, Gabriel; Wilensky, Asaf; Hovav, Avi-Hai

2017-01-10

Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4 + T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SMS Advertising in India: Is TAM a Robust Model for Explaining Intention?

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Hemant Bamoriya

2012-06-01

Full Text Available This study examined mobile users’ intentions to receive SMS advertising in India using Technology Acceptance Model (TAM as research framework. 242 respondents completed a structured questionnaire; measuring their responses for the TAM’s five constructs viz. perceived utility, perceived ease of use, perceived trust, attitude and intention. Using Structural Equation Modeling (SEM both measurement model and structural model testing was done to analyze the data. Findings indicated that specified TAM model contributed to 81.8% of variance in the intention to receive SMS advertising and was a valid model in explaining the intention to receive SMS advertising. Study further indicated that perceived utility was much better predictor of attitude towards SMS advertising than perceived ease of use and perceived trust. Study suggested marketers that to increase acceptance of SMS advertising they should focus more on increasing utility of SMS ads, so that users would develop positive attitudes towards SMS advertising.

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

Science.gov (United States)

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

2014-10-10

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors

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Abdellah Messoussi

2014-10-01

Full Text Available Structural elucidation of the active (DFG-Asp in and inactive (DFG-Asp out states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

Penelitian Perilaku Pengguna Internet Pada Desa Pinter Hasil Pembangunan USO dengan Pendekatan Technology Acceptance Model (TAM di Provinsi Jawa Tengah

Directory of Open Access Journals (Sweden)

Lasni Julita Siahaan

2011-03-01

Full Text Available Fasilitas internet yang dibangun dengan proyek USO adalah suatu teknologi baru yang dapat menimbulkan reaksi pada penggunanya, baik reaksi menerima maupun reaksi menolak. Oleh karena itu, perlu diketahui model penerimaan teknologi tersebut serta factor-faktor yang berpengaruh terhadap penerimaanya. Salah satu model penerimaan pemakai terhadap teknologi yang paling sesuai sampai sekarang adalah technology acceptance model (TAM yang dikemukakan oleh Davis dan Khosrow-Pour (2006: 209. Bagaimana kecocokan model TAM dalam menilai penerimaan pengguna terhadap fasilitas internet tersebut dianalisis dengan structural equation modeling (SEM. Pendekatan dalam penelitian ini adalan kuantitatif dengan melakukan survey kepada masyarakat di sekitar lokasi pembangunan proyek USO di Propinsi Jawa Tengah. Hasil penelitian menunjukkan bahwa model TAM dapat digunakan menilai perilaku masyarakat di sekitar lokasi pembangunan proyek USO dalam menerima dan memanfaatkan fasilitas Internet.

PENERAPAN MODIFIKASI TECHNOLOGY ACCEPTANCE MODEL (TAM) DALAM E-BUSINESS

OpenAIRE

Adi Setiawan; Lisa Harry Sulistiowati

2018-01-01

This study analyzed SMEs batik entrepreneurs in Cirebon to apply e-business. The TAM3 theory is used to create an analytical model in understanding the desires of the entrepreneur. The desire to use technology is due to the perception of the level of ease of use. The easier the user perception, the higher the ability to see the usefulness of technology, and the easier the perception of usage, the higher desire to utilize technology. The analysis result shows that perceived ease of use is in m...

Late Quaternary extinctions: The promise of TAMS 14C dating

International Nuclear Information System (INIS)

Martin, P.S.

1987-01-01

In the last 30 000 years late Quaternary extinctions eliminated over two-thirds of the large land mammals of America and Australia and most of the endemic land vertebrates on oceanic islands. Specimens of extinct animals yielding too little organic material for measurement in decay counters are suitable for TAMS dating. Initial results support older evidence of an extinction chronology that was catastrophic regionally, transgressive globally, and linked to the spread of prehistoric people. (orig.)

Extended TAM Model: Impacts of Convenience on Acceptance and Use of Moodle

Science.gov (United States)

Hsu, Hsiao-hui; Chang, Yu-ying

2013-01-01

The increasing online access to courses, programs, and information has shifted the control and responsibility of learning process from instructors to learners. Learners' perceptions of and attitudes toward e-learning constitute a critical factor to the success of such system. The purpose of this study is to take TAM (technology acceptance model)…

A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.

Science.gov (United States)

Anosova, Irina; Melnik, Svitlana; Tripsianes, Konstantinos; Kateb, Fatiha; Grummt, Ingrid; Sattler, Michael

2015-05-26

The chromatin remodeling complex NoRC, comprising the subunits SNF2h and TIP5/BAZ2A, mediates heterochromatin formation at major clusters of repetitive elements, including rRNA genes, centromeres and telomeres. Association with chromatin requires the interaction of the TAM (TIP5/ARBP/MBD) domain of TIP5 with noncoding RNA, which targets NoRC to specific genomic loci. Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins. However, the TAM domain exhibits an extended MBD fold with unique C-terminal extensions that constitute a novel surface for RNA binding. Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo. Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

DOE Project 353: TAMS Prototype and production coupling alignment units

Energy Technology Data Exchange (ETDEWEB)

Field, K.V.

1996-02-01

TAMS is an electronic measurement system used to determine the alignment of turbine-generator shafts at the coupling interface. The displacement transducer is a strain gage based sensor mounted in a portable probe. The measurement system was experiencing zero input drift and temperature induced drift. This project endeavored to determine the source of these problems and to revise a unit to be returned to a customer, Baltimore Gas and Electric (BGE), within a period of five weeks.

OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

Science.gov (United States)

Cromer, Laurence; Heyman, Jefri; Touati, Sandra; Harashima, Hirofumi; Araou, Emilie; Girard, Chloe; Horlow, Christine; Wassmann, Katja; Schnittger, Arp; De Veylder, Lieven; Mercier, Raphael

2012-01-01

Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especially required for exit from mitosis. We have shown previously that OSD1 is involved in entry into both meiosis I and meiosis II in Arabidopsis thaliana; however, the molecular mechanism by which OSD1 controls these transitions has remained unclear. Here we show that OSD1 promotes meiotic progression through APC/C inhibition. Next, we explored the functional relationships between OSD1 and the genes known to control meiotic cell cycle transitions in Arabidopsis. Like osd1, cyca1;2/tam mutation leads to a premature exit from meiosis after the first division, while tdm mutants perform an aberrant third meiotic division after normal meiosis I and II. Remarkably, while tdm is epistatic to tam, osd1 is epistatic to tdm. We further show that the expression of a non-destructible CYCA1;2/TAM provokes, like tdm, the entry into a third meiotic division. Finally, we show that CYCA1;2/TAM forms an active complex with CDKA;1 that can phosphorylate OSD1 in vitro. We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor.

Development of CANDLES low background HPGe detector and half-life measurement of 180Tam

Science.gov (United States)

Chan, W. M.; Kishimoto, T.; Umehara, S.; Matsuoka, K.; Suzuki, K.; Yoshida, S.; Nakajima, K.; Iida, T.; Fushimi, K.; Nomachi, M.; Ogawa, I.; Tamagawa, Y.; Hazama, R.; Takemoto, Y.; Nakatani, N.; Takihira, Y.; Tozawa, M.; Kakubata, H.; Trang, V. T. T.; Ohata, T.; Tetsuno, K.; Maeda, T.; Khai, B. T.; Li, X. L.; Batpurev, T.

2018-01-01

A low background HPGe detector system was developed at CANDLES Experimental Hall for multipurpose use. Various low background techniques were employed, including hermatic shield design, radon gas suppression, and background reduction analysis. A new pulse shape discrimination (PSD) method was specially created for coaxial Ge detector. Using this PSD method, microphonics noise and background event at low energy region less than 200 keV can be rejected effectively. Monte Carlo simulation by GEANT4 was performed to acquire the detection efficiency and study the interaction of gamma-rays with detector system. For rare decay measurement, the detector was utilized to detect the nature's most stable isomer tantalum-180m (180Tam) decay. Two phases of tantalum physics run were completed with total livetime of 358.2 days, which Phase II has upgraded shield configuration. The world most stringent half-life limit of 180Tam has been successfully achieved.

Evaluation Study of the Tactical Atmospheric Modeling System/Real-Time (TAMS-RT) at NPMOC San Diego

National Research Council Canada - National Science Library

Reiss, Arthur

1999-01-01

...) has been developed by the Naval Research Lab in Monterey, California to meet this task. A forecast system employing COAMPS, called the Tactical Atmospheric Mesoscale System- Real Time (TAMS-RT...

Assessing the utility of TAM, TPB, and UTAUT for advanced driver assistance systems.

Science.gov (United States)

Rahman, Md Mahmudur; Lesch, Mary F; Horrey, William J; Strawderman, Lesley

2017-11-01

Advanced Driver Assistance Systems (ADAS) are intended to enhance driver performance and improve transportation safety. The potential benefits of these technologies, such as reduction in number of crashes, enhancing driver comfort or convenience, decreasing environmental impact, etc., have been acknowledged by transportation safety researchers and federal transportation agencies. Although these systems afford safety advantages, they may also challenge the traditional role of drivers in operating vehicles. Driver acceptance, therefore, is essential for the implementation of these systems into the transportation system. Recognizing the need for research into the factors affecting driver acceptance, this study assessed the utility of the Technology Acceptance Model (TAM), the Theory of Planned Behavior (TPB), and the Unified Theory of Acceptance and Use of Technology (UTAUT) for modelling driver acceptance in terms of Behavioral Intention to use an ADAS. Each of these models propose a set of factors that influence acceptance of a technology. Data collection was done using two approaches: a driving simulator approach and an online survey approach. In both approaches, participants interacted with either a fatigue monitoring system or an adaptive cruise control system combined with a lane-keeping system. Based on their experience, participants responded to several survey questions to indicate their attitude toward using the ADAS and their perception of its usefulness, usability, etc. A sample of 430 surveys were collected for this study. Results found that all the models (TAM, TPB, and UTAUT) can explain driver acceptance with their proposed sets of factors, each explaining 71% or more of the variability in Behavioral Intention. Among the models, TAM was found to perform the best in modelling driver acceptance followed by TPB. The findings of this study confirm that these models can be applied to ADAS technologies and that they provide a basis for understanding driver

The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

Science.gov (United States)

Park, Hyun-Jung; Baen, Ji-Yeon; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee

2012-08-01

The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small interfering RNA (siRNA), and a recombinant Mer protein (Mer/Fc) inhibited HGF mRNA and protein expression, as well as activation of RhoA, Akt, and specific mitogen-activated protein (MAP) kinases in response to apoptotic cells. Inhibition of Axl or Tyro3 with specific antibodies, siRNA, or Fc-fusion proteins did not prevent apoptotic cell-induced HGF mRNA and protein expression and did not inhibit activation of the postreceptor signaling molecules RhoA and certain MAP kinases, including extracellular signal-regulated protein kinase and c-Jun NH(2)-terminal kinase. However, Axl- and Tyro3-specific blockers did inhibit the activation of Akt and p38 MAP kinase in response to apoptotic cells. In addition, none of the TAM receptors mediated the effects of apoptotic cells on transforming growth factor-β or epidermal growth factor mRNA expression. However, they were involved in the induction of vascular endothelial growth factor mRNA expression. Our data provide evidence that when macrophages interact with apoptotic cells, only Mer of the TAM-family receptors is responsible for mediating transcriptional HGF production through a RhoA-dependent pathway.

Towards controlled mutagenesis with transposons Ac and Tam3

Energy Technology Data Exchange (ETDEWEB)

Haring, M; Veken, J; Windrich, R; Kneppers, T; Rommens, C; Nijkamp, H J.J.; Hille, J [Department of Genetics, Free University, Amsterdam (Netherlands)

1990-01-01

Full text: The discovery of mobile genetic elements in plants has permitted the use of these transposons for insertional mutagenesis. This applies so far only to Zea mays and Antirrhinum majus, because other plant transposable elements have not been characterised so thoroughly at the genetic and the molecular level. To establish whether transposons (Ac from maize and Tam3 from Antirrhinum) remain mobile in heterologous hosts, either in somatic tissue or after meiosis, a phenotypic assay system for transposition was developed. The separation of the two transposition functions will allow controlled mutagenesis of plant genes. Our results indicate that both transposable elements remain active in heterologous hosts. (author)

Kajian Penerimaan Pengguna Terhadap Sistem CRM di Perusahaan X Menggunakan Model TAM

Directory of Open Access Journals (Sweden)

Muhammad Malik Hakim

2018-03-01

Full Text Available Pelayanan kepada pelanggan adalah salah satu tujuan bisnis setiap perusahaan dalam upayanya memberikan kepuasan kepada para pelanggannya. Untuk mengintegrasikan seluruh kegiatan pelayanan kepada pelanggan dari semua divisi yang terkait baik langsung maupun tidak langsung, Perusahaan X sebagai perusahaan yang bergerak dalam bidang TI telah mengimplementasikan sistem CRM (Customer Relationship Management. Implementasi CRM tersebut bertujuan untuk mensinergikan kegiatan pelayanan kepada pelanggan agar tidak saling tumpang tindih dan dapat terkoordinasi dengan baik. Untuk mendukung kesuksesan dan keberlanjutan penggunaan sistem CRM, penelitian ini mengkaji penerimaan pengguna sistem CRM di antara semua karyawan dalam divisi terkait di dalam perusahaan yang berjumlah 141 orang, menggunakan Model TAM (Technology Acceptance Model yang dimodifikasi, yaitu tanpa melibatkan variabel eksternal. Penelitian ini mengkaji penerimaan pengguna berdasarkan empat variabel penyusun Model TAM, yaitu Perceived Ease Of Use (PEOU, Perceived Usefulness (PU, Behavioral Intention (BI, dan Actual Use (AU. Studi membuktikan bahwa diperoleh pengaruh yang positif dan signifikan antara variabel – variabel penyusunnya, yaitu PEOU terhadap PU dan BI, PU terhadap BI, serta BI terhadap AU dengan nilai pengaruh masing – masing adalah 0,43; 0,67; 0,58; dan 0,77. Penelitian ini membuktikan bahwa penerimaan pengguna CRM sangat dipengaruhi oleh faktor manfaat, kemudahan, serta perilaku karyawan dalam menggunakannya.

Understanding intention to use electronic information resources: A theoretical extension of the technology acceptance model (TAM).

Science.gov (United States)

Tao, Donghua

2008-11-06

This study extended the Technology Acceptance Model (TAM) by examining the roles of two aspects of e-resource characteristics, namely, information quality and system quality, in predicting public health students' intention to use e-resources for completing research paper assignments. Both focus groups and a questionnaire were used to collect data. Descriptive analysis, data screening, and Structural Equation Modeling (SEM) techniques were used for data analysis. The study found that perceived usefulness played a major role in determining students' intention to use e-resources. Perceived usefulness and perceived ease of use fully mediated the impact that information quality and system quality had on behavior intention. The research model enriches the existing technology acceptance literature by extending TAM. Representing two aspects of e-resource characteristics provides greater explanatory information for diagnosing problems of system design, development, and implementation.

Examining the Antecedents of ICT Adoption in Education Using an Extended Technology Acceptance Model (TAM)

Science.gov (United States)

Teeroovengadum, Viraiyan; Heeraman, Nabeel; Jugurnath, Bhavish

2017-01-01

This study assesses the determinants of ICT adoption by educators in the teaching and learning process in the context of a developing country, Mauritius. A hierarchical regression analysis is used, to firstly determine the incremental effects of factors from the technology acceptance model (TAM) while controlling for demographic variables such as…

Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: correlation with disease activity and bone destruction.

Science.gov (United States)

Xu, L; Hu, F; Zhu, H; Liu, X; Shi, L; Li, Y; Zhong, H; Su, Y

2018-04-01

The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in patients with RA. A total of 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled into this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by enzyme-linked immunosorbent assay (ELISA), then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analysed. We also investigated whether sTyro3 could promote osteoclast differentiation in vitro in RA patients. The results showed that compared with healthy controls (HCs), sTyro3 levels in the serum of RA patients were elevated remarkably and sMer levels were decreased significantly, whereas there was no difference between HCs and RA patients on sAxl levels. The sTyro3 levels were correlated weakly but positively with white blood cells (WBC), immunoglobulin (Ig)M, rheumatoid factor (RF), swollen joint counts, tender joint counts, total sharp scores and joint erosion scores. Conversely, there were no significant correlations between sMer levels and the above indices. Moreover, RA patients with high disease activity also showed higher sTyro3 levels. In-vitro osteoclast differentiation assay showed further that tartrate-resistant acid phosphatase (TRAP) + osteoclasts were increased significantly in the presence of sTyro3. Collectively, our study indicated that serum sTyro3 levels were elevated in RA patients and correlated positively with disease activity and bone destruction, which may serve as an important participant in RA pathogenesis. © 2017 British Society for Immunology.

Pengaruh Gadget Terhadap Prestasi Siswa SMK Yayasan Islam Tasikmalaya Dengan Metode TAM

Directory of Open Access Journals (Sweden)

Arif Rifan Hidayat

2017-09-01

Full Text Available Abstrak Gadget merupakan suatu barang dengan berbagai aplikasi yang dapat menyajikan berbagai media berita, jejaring sosial, hobi, bahkan hiburan. Prestasi belajar adalah hasil atau taraf kemampuan yang telah dicapai siswa setelah mengikuti proses belajar mengajar dalam waktu tertentu, baik berupa perubahan tingkah laku, keterampilan, dan pengetahuan. Kemudian akan diukur dan dinilai dalam angka atau pernyataan. Tujuan penelitian ini untuk mengetahui pengaruh gadget terhadap prestasi siswa di SMK Yayasan Islam Tasikmalaya. Metode penelitian yang digunakan yaitu dengan metode Technology Acceptance Model (TAM dengan 3 konstruk, yaitu persepsi pengguna terhadap manfaat (perceived usefulness, persepsi pengguna terhadap penggunaan (perceived ease of use dan persepsi sikap terhadap penggunaan (attitude toward using. Populasi penelitian ini adalah Siswa kelas X dan XI  SMK Yayasan Islam Tasikmalaya sebanyak 100 orang. Instrumen yang digunakan dalam penelitian ini adalah kuesioner. Berdasarkan hasil penelitian dan pengujian hipotesis didapatkan hasil pengujian fhitung adalah 1,157. Persamaan hipotesis menyatakan bahwa nilai signifikasinya sebesar 0,319 > α 0,05 lebih besar dari ftabel. Dengan demikian dikatakan bahwa H0 diterima dan Ha ditolak, sehingga hipotesis berbunyi terdapat pengaruh yang signifikan antara variabel perceived usefulness (X1, dan perceived ease of use (X2 terhadap Attitude Toward Using (Y secara simultan. Pengaruh Perceived Usefulness (X1 dan Perceived Ease Of Use (X2 secara bersama-sama terhadap Attitude Toward Using (Y adalah sebesar 2,3%, dan sisanya sebesar 97,7% merupakan pengaruh yang diberikan oleh variabel lain diluar model atau penelitian ini.   Kata Kunci: TAM , Gadget, Prestasi. Abstract Gadgets are an item with various applications that can present various news media, social networking, hobbies, even entertainment. Learning achievement is the result or level of ability that has been achieved by students after

Les gens, et non les choses, calment les eaux de la lagune de Tam ...

International Development Research Centre (IDRC) Digital Library (Canada)

Cathy Egan

La lagune de Tam Giang au Viet Nam est un habitat naturel presque parfait pour la pêche et l'aquaculture. Longue de plus de 70 km et d'une profondeur moyenne d'à peine deux mètres, la lagune est un milieu des plus productifs, tant pour les espèces d'eau douce que pour les espèces marines. Au cours des dernières ...

Validating the Satisfaction and Continuance Intention of E-Learning Systems: Combining TAM and IS Success Models

Science.gov (United States)

Lin, Tung-Cheng; Chen, Ching-Jen

2012-01-01

Many e-learning studies have evaluated learning attitudes and behaviors, based on TAM. However, a successful e-learning system (ELS) should take both system and information quality into account by applying ISM developed by Delone and McLean. In addition, the acceptance for information system depends on the perceived usefulness and ease of use…

Bomb conversion of CO2 to graphite for radiocarbon measurement by tandem accelerator mass spectrometry (TAMS)

International Nuclear Information System (INIS)

Lowe, D.C.; Judd, W.J.

1985-01-01

TAMS has extended the scope of radiocarbon dating but improved sample target preparation techniques are still required. In this paper a quick and reliable method for the conversion of CO 2 into graphite targets suitable for radiocarbon dating is presented. In the outlined procedure a single operator can produce 20 graphite targets a day. (author)

Preparation of graphite targets for radiocarbon dating by tandem accelerator mass spectrometer (TAMS)

International Nuclear Information System (INIS)

Lowe, D.C.

1984-01-01

The introduction of TAMS has exciting implications for radiocarbon dating but improved sample preparation methods are needed. This paper describes a promising method for the conversion of a few milligrams of wood or charcoal into graphite targets for use in a caesium sputter ion source. Targets containing a large proportion of G-type graphite produced large C - currents, but those containing a high proportion of turbostatic Tn graphite were unsatisfactory; the type of graphite in the target is clearly of significance. (author)

INTEGRASI-INTERKONEKSI ILMU PERSPEKTIF TAFSIR SOSIAL TAM (TUHAN ALAM DAN MANUSIA

Directory of Open Access Journals (Sweden)

Imron Muttaqin

2014-12-01

Full Text Available As a great project, the integration and the inter-connection knowledge need a complex system include philosophy that combine the substantive and position of God (meta-cosmos, macro-cosmos (Nature, and micro-cosmos (The human. The knowledge dichotomy in Islam must be reunited by integration and inter-connection, but that efforts need setting of the mindset to avoid an error logical thinking of understanding about substantive, position and goal. The Social Tafseer TAM (God, Nature and Human is one of alternative way to build the Islamic true logical thinking because it has many purposes in finding Allah`s blessing and also a systematic characteristic in the processes.

The limitations of using the existing TAM in adoption of clinical decision support system in hospitals: An empirical study in Malaysia

Directory of Open Access Journals (Sweden)

Pouyan Esmaeilzadeh

2014-04-01

Full Text Available The technology acceptance model (TAM has been widely used to study user acceptance of new computer technologies. Previous studies claimed that future technology acceptance research should explore other additional explanatory variables, which may affect the originally proposed constructs of the TAM. The use of information technology in the health care sector and especially in hospitals offers great potential for improving the performance of physicians, increasing the quality of services and also reducing the organizational expenses. However, the main challenge that arises according to the literature is whether healthcare professionals are willing to adopt and use clinical information technology while performing their tasks. Although adoption of various information technologies has been studied using the technology acceptance model (TAM, the study of technology acceptance for professional groups (such as physicians has been limited. Physician adoption of clinical information technology is important for its successful implementation. Therefore, the purpose of this study is to gain a better insight about factors affecting physicians’ acceptance of clinical decision support systems (CDSS in a hospital setting. The results reflect the importance of perceived threat to professional autonomy, perceived interactivity with clinical IT, perceived usefulness and perceived ease of use in determining physicians’ intention to use CDSS.

Anticancer effect of luteolin is mediated by downregulation of TAM receptor tyrosine kinases, but not interleukin-8, in non-small cell lung cancer cells.

Science.gov (United States)

Lee, Youn Ju; Lim, Taeho; Han, Min Su; Lee, Sun-Hwa; Baek, Suk-Hwan; Nan, Hong-Yan; Lee, Chuhee

2017-02-01

TAM receptor tyrosine kinases (RTKs), Tyro3, Axl and MerTK, transduce diverse signals responsible for cell survival, growth, proliferation and anti-apoptosis. In the present study, we demonstrated the effect of luteolin, a flavonoid with antioxidant, anti-inflammatory and anticancer activities, on the expression and activation of TAM RTKs and the association with its cytotoxicity in non-small cell lung cancer (NSCLC) cells. We observed the cytotoxic effect of luteolin in parental A549 and H460 cells as well as in cisplatin-resistant A549/CisR and H460/CisR cells. Exposure of these cells to luteolin also resulted in a dose‑dependent decrease in clonogenic ability. Next, luteolin was found to decrease the protein levels of all three TAM RTKs in the A549 and A549/CisR cells in a dose‑dependent manner. In a similar manner, in H460 and H460/CisR cells, the protein levels of Axl and Tyro3 were decreased following luteolin treatment. In addition, Axl promoter activity was decreased by luteolin, indicating that luteolin suppresses Axl expression at the transcriptional level. We next found that luteolin abrogated Axl phosphorylation in response to growth arrest-specific 6 (Gas6), its ligand, implying the inhibitory effect of luteolin on Gas6-induced Axl activation. Ectopic expression of Axl was observed to attenuate the antiproliferative effect of luteolin, while knockdown of the Axl protein level using a gold nanoparticle-assisted gene delivery system increased its cytotoxicity. In contrast to the inhibitory effect of luteolin on the expression of TAM RTKs, interleukin-8 (IL-8) production was not decreased by luteolin in H460 and H460/CisR cells, while IL-8 production/cell was increased. Collectively, our data suggest that TAM RTKs, but not IL-8, are promising therapeutic targets of luteolin to abrogate cell proliferation and to overcome chemoresistance in NSCLC cells.

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity.

Science.gov (United States)

Recarte-Pelz, Pedro; Tàssies, Dolors; Espinosa, Gerard; Hurtado, Begoña; Sala, Núria; Cervera, Ricard; Reverter, Joan Carles; de Frutos, Pablo García

2013-03-12

Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE.

EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.

Science.gov (United States)

Boś-Liedke, Agnieszka; Walawender, Magdalena; Woźniak, Anna; Flak, Dorota; Gapiński, Jacek; Jurga, Stefan; Kucińska, Małgorzata; Plewiński, Adam; Murias, Marek; Elewa, Marwa; Lampp, Lisa; Imming, Peter; Tadyszak, Krzysztof

2018-06-01

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

Consumer acceptance of a quick response (QR) code for the food traceability system: Application of an extended technology acceptance model (TAM).

Science.gov (United States)

Kim, Yeong Gug; Woo, Eunju

2016-07-01

The objectives of this study are to apply the TAM using the addition of perceived information to individuals' behavioral intention to use the QR code for the food traceability system; and to determine the moderating effects of food involvement on the relationship between perceived information and perceived usefulness. Results from a survey of 420 respondents are analyzed using structural equation modeling. The study findings reveal that the extended TAM has a satisfactory fit to the data and that the underlying dimensions have a significant effect on consumers' intention to use the QR code for the food traceability system. In addition, food involvement plays a significant moderating function in the relationship between perceived information and perceived usefulness. The implications of this study for future research are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

PENERAPAN MODIFIKASI TECHNOLOGY ACCEPTANCE MODEL (TAM DALAM E-BUSINESS

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Adi Setiawan

2018-03-01

Full Text Available This study analyzed SMEs batik entrepreneurs in Cirebon to apply e-business. The TAM3 theory is used to create an analytical model in understanding the desires of the entrepreneur. The desire to use technology is due to the perception of the level of ease of use. The easier the user perception, the higher the ability to see the usefulness of technology, and the easier the perception of usage, the higher desire to utilize technology. The analysis result shows that perceived ease of use is in medium and low category. Perceived usefulness is in the high and medium category. The desire to behavioral intention to use is in the medium and low category. The result of hypothesis testing shows the perception of ease of influence perception of usefulness. Furthermore, perceptions of usefulness affect the desire to use technology in business activities. The test result shows the perception of ease that doesn’t give a direct significant influence to the desire to use technology.

Studying RFID Consumer Acceptance Using TAM: the Case of IUST Students

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Ahad Zare Ravasan

2012-02-01

Full Text Available Radio frequency identification (RFID technology is used in numerous applications and offers a plethora of interesting potential new applications. However, this potential raises issues that require addressing to achieve its widespread acceptance by consumers. This paper investigated the factors that affect consumer acceptance of RFID technology using the technology acceptance model (TAM. To this end, a questionnaire was prepared and distributed among Iran University of Science and Technology (IUST students and gathered data were analyzed using multivariable linear regression method. The results proposed that convenience, culture, and regulation were the principal factors influencing the consumers’ acceptance of RFID. The results of the paper can provide insight to organizations in providing RFID enabled products to their customers and also facilitated its development in the society.

User adoption of mobile commerce in Bangladesh: Integrating perceived risk, perceived cost and personal awareness with TAM

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Mohammed Mizanur Rahman

2017-04-01

Full Text Available This paper develops and tests a model for predicting user adoption of mobile commerce (i.e. e-commerce using mobile phones in developing countries. The model takes up the Technology Acceptance Model (TAM determinants of perceived usefulness and perceived ease of use, and extends these through the inclusion of three further determinants: perceived risk, perceived cost and personal awareness to enable prediction of the likelihood of mobile commerce adoption by users in the developing world. 575 usable surveys were gathered from the urban, semi-urban and rural areas of Bangladesh. Perceived risk and perceived usefulness were found to be the most influential factors effecting mobile commerce adoption, while the effect of perceived ease of use and personal awareness was found to be low although significant. The study reconfirmed the need of extending TAM model, in the context of mobile commerce, to address both itrs transactional and non-transactional components. Service providers need to ensure high levels of security and privacy to reduce userrs perceptions of risk. Mobile commerce services and technologies should be upgraded to world standard to make them more useful to users.

ANALISIS PENERIMAAN E-LEARNING MENGGUNAKAN TECHNOLOGY ACCEPTANCE MODEL (TAM (STUDI KASUS: UNIVERSITAS ATMA JAYA YOGYAKARTA

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Flourensia Sapty Rahayu

2017-11-01

Full Text Available Dalam implementasi sebuah sistem informasi di suatu institusi, perlu dipertimbangkan  bagaimana penerimaan pengguna terhadap sistem informasi tersebut. Penerapan sistem informasi dapat dikatakan gagal jika pengguna ternyata tidak dapat menerima atau tidak mau menggunakan sistem informasi tersebut. Sebagai sebuah institusi pendidikan, Universitas Atma Jaya Yogyakarta (UAJY juga mengimplementasikan sistem e-learning untuk mendukung proses belajar mengajar. Pengguna wajib dari e-learning ini adalah dosen dan mahasiwa. Sejak diterapkan belum pernah diadakan evaluasi mengenai penerimaan pengguna terhdap sistem e-learning ini. Penelitian ini dilakukan untuk melakukan pengujian terhadap penerimaan pengguna (mahasiswa terhadap e-learning dengan menggunakan Technology Acceptance Model (TAM. Pengujian dilakukan dengan mengukur pengaruh antar variabel dalam model TAM yang meliputi variabel Perceived Ease of Use, Perceived Usefulness, Attitude Toward Using, Behavioral Intention dan Actual Usage. Metode pengujian statistik yang dilakukan yaitu uji statistik validitas, reliabilitas, normalitas, dan menguji pengaruh faktor menggunakan Structural Equation Model (SEM. Sumber data didapatkan dengan metode kuesioner yang dibagikan kepada responden mahasiswa UAJY dari seluruh fakultas. Dari enam hipotesis yang diajukan satu hipotesis dinyatakan tidak diterima, yaitu hipotesis yang menyatakan Perceived Usefulnes berpengaruh terhadap Behavioral Intention. Kelima hipotesis yang lain yaitu Perceived Ease of Use berpengaruh terhadap Perceived Usefulnes, Perceived Usefulnes berpengaruh terhadap Attitude Toward Using, Perceived Ease of Use berpengaruh terhadap Attitude Toward Using, Attitude Toward Using berpengaruh terhadap Behavioral Intention, Behavioral Intention berpengaruh terhadap Actual Usage dinyatakan dapat diterima.

Climatic change and health. Which problems are caused by thermophile hazardous organisms? Final report. Environment and health: climatic change; Klimawandel und Gesundheit. Welche Probleme verursachen Waerme liebende Schadorganismen? Abschlussbericht. Umwelt and Gesundheit: Klimawandel

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Augustin, Jobst; Muecke, Hans-Guido (comps.)

2010-03-15

Climatic changes can cause health hazards due to thermophile harmful organisms, especially those with increased allergic potentials. The meeting covered the following topics: climatic change induced health hazards and the German adaptation strategies; the complex relation between climatic change and allergies; ambrosia propagation in Germany - hazards for health and biodiversity; climatic change induced reaction of hygienically precarious organism in urban regions; monitoring and abatement of Thaumetopoea processionea in Bavarian woods; climatic change and pollen flight dynamics; Thaumetopoea processionea as cause for non-distinctive respiratory systems diseases; risk and protection factors for the development of asthma and allergies during infancy; abatement of pathogenic or invasive harmful organisms in Switzerland; health hazards in connection with Thaumetopoea processionea - examples from Bavaria; retrospective analysis of EPS diseases during 2004 and 2005 in the region Kleve.

TAM MALİYET VE NORMAL MALİYET YÖNTEMLERİNİN UFRS (TFRS) VE BOBİ FRS’DEKİ DÜZENLEMELER ÇERÇEVESİNDE İNCELENMESİ

OpenAIRE

Gökçen, Gürbüz; ÖZTÜRK, Erkan

2018-01-01

Tam maliyet yöntemi güvenilir bir ölçümlemearacı olarak kabul edilmesi nedeniyle uzun yıllar boyunca birçok işletmetarafından kullanılmıştır. Bununla birlikte, maliyet ölçümlemesinde yöntemineksik yanları zaman içerisinde tespit edilmiş ve alternatif yöntemlergeliştirilmiştir. Günümüzde Uluslararası Finansal Raporlama Standartları (UFRS)setinde ve bu setin Türkçe tercümesi olan Türkiye Finansal RaporlamaStandartları (TFRS) setinde maliyet ölçümlemesinin tam maliyet yöntemi yerinenormal maliye...

Polychlorinated biphenyls in sediments of the Tam Giang-Cau Hai Lagoon (Central Vietnam). First results

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Frignani, M.; Bellucci, L.G.; Albertazzi, S. [Istituto di Scienze Marine, Sezione di Geologia Marina, CNR, Bologna (Italy); Piazza, R.; Moret, I. [Univ. Ca Foscari, Venezia (Italy). Dip. Scienze Ambientali; Huu, Cu Nguyen [Haiphong Institute of Oceanology, Haiphong City (Viet Nam); Zangrando, R. [Istituto per la Dinamica dei Processi Ambientali, CNR, Venezia (Italy)

2004-09-15

The Tam Giang-Cau Hai (TG-CH) Lagoon, a typical tropical coastal wetland, is the largest in southeast Asia, being 70 km long with a surface of 216 km{sup 2}. This system is quite complex because it is composed of four parts with different shapes and extension called Pha Tam Giang (27 km long, 0.6-3.5 km wide, up to 2m deep), Dam Sam-An Truyen (5x5.5 km, 2 m deep), Dam Thuy Tu (24.5 km long, 0.8-2.6 km wide, up to 4 m deep) and Dam Cau Hai (a southernmost, semi circular basin 17 km wide and 1-1.5 m deep). Characteristics and problems of the TG-CH lagoon were extensively described by Frignani et al. In particular, this environment is now facing many critical problems such as oil pollution, coliform contamination, eutrophication and presence of anthropogenic chemicals. This situation requires a management, capable to reverse the negative trend, that should be based on a sound scientific background. However, so far, the research-based knowledge on the key environmental processes and the levels, sources and trends of contamination is rather poor, especially regarding the most dangerous organic species. The purpose of this work was to provide a first insight on the presence of PCBs in lagoon sediments with a particular attention to the history and trends of the inputs.

The Influence of Technology Acceptance Model (TAM on The Users’ Behavior of Sikesya Application in IAIN Surakarta

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Tri Wahyuni

2016-04-01

Full Text Available This study aims to evaluate the student acceptance of SIKESYA  (Sharia Financial System/Sikesya application as the users by using the framework of Technology Acceptance Model (TAM and its development. The constructs being tested in this research are perceived usefulness, perceived ease of use, experience, social influence, attitute toward behavior, behavioral intention, facilitating condition, and user behaviors. As much as 80 students has been chosen as sample which were determined using purposive sampling method. The data gathered was then analyzed using partial least square (PLS. The result showed that experience did not influence the perceived ease of use, on the other hand perceived usefulness has a positif influence toward users attitude and behavior in using Sikesya, while the perceived ease of use did not influence the users atttitude and  behavior at all, since the students would still use it as it is an application used as part of university services. The attitude and behavior did not influence the behavioral intention, whereas the social influence has a positif effect on behavioral intention, yet the behavioral intention gave positif impact to user’s behavior. On the other hand, facilitating condition has no effect toward users’ behavior.   Keywords: Sharia Financial System (SIKESYA, Technology Acceptance Model (TAM, IAIN Surakarta

Investigating the Effect of Learning Styles in a Blended E-Learning System: An Extension of the Technology Acceptance Model (TAM)

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Al-Azawei, Ahmed; Parslow, Patrick; Lundqvist, Karsten

2017-01-01

This study assesses learner perceptions of a blended e-learning system (BELS) and the feasibility of accommodating educational hypermedia systems (EHSs) according to learning styles using a modified version of the technology acceptance model (TAM). Recently, Moodle has been adopted by an Iraqi university alongside face-to-face (F2F) classrooms to…

Exploring the Intrinsic Motivation of Hedonic Information Systems Acceptance: Integrating Hedonic Theory and Flow with TAM

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Wang, Zhihuan

Research on Information Systems (IS) acceptance is substantially focused on extrinsic motivation in workplaces, little is known about the underlying intrinsic motivations of Hedonic IS (HIS) acceptance. This paper proposes a hybrid HIS acceptance model which takes the unique characteristics of HIS and multiple identities of a HIS user into consideration by interacting Hedonic theory, Flow theory with Technology Acceptance Model (TAM). The model was empirically tested by a field survey. The result indicates that emotional responses, imaginal responses, and flow experience are three main contributions of HIS acceptance.

Development of a new monitor for tritium in air model TAM-II

International Nuclear Information System (INIS)

Wu Bin; Yang Hailan; Wen Xuelian; Zhao Yi; Yang Huaiyuan

2001-01-01

The author introduces development of a real-time continuous tritium monitor model TAM-II. The detector of the instrument is comprised of four geometric-symmetry open wall ionization chamber with the effective volume of 2 L, which enables to minimize the remember effect of the ionization chamber due to contamination by the monitored tritium. It is γ background compensation rate is better than 97% in almost all direction. The detector is equipped with a FET static electrometer working in micro-current integration mode. The measurement process of the tritium monitor can be controlled automatically by a micro-processor sheet, such as automatic range changing, data displaying and storing, and data processing. The measuring range is 6 - 10 6 Bq/L. It is especially application for monitoring tritium in off-gas effluence from glove-box or stack of tritium facility and laboratory

University staff adoption of iPads: An empirical study using an extended TAM model

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Michael Steven Lane

2014-11-01

Full Text Available This research examined key factors influencing adoption of iPads by university staff. An online survey collected quantitative data to test hypothesised relationships in an extended TAM model. The findings show that university staff consider iPads easy to use and useful, with a high level of compatibility with their work. Social status had no influence on their attitude to using an iPad. However older university staff and university staff with no previous experience in using a similar technology such as an iPhone or smartphone found iPads less easy to use. Furthermore, a lack of formal end user ICT support impacted negatively on the use of iPads.

Diversity of Andean amphibians of the Tamá National Natural Park in Colombia: a survey for the presence of Batrachochytrium dendrobatidis

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Acevedo, A.A.; Franco, R.; Carrero, D.A.

2016-07-01

Changes in diversity and possible decreases in populations of amphibians have not yet been determined in many areas in the Andes. This study aimed to develop an inventory of the biodiversity of amphibians in the Andean areas of the Tamá National Natural Park (Tamá NNP) and to evaluate the patterns of infection by Batrachochytrium dendrobatidis (Bd) in preserved and degraded areas. We performed samplings focused on three habitats (forest, open areas and streams) in four localities from 2,000 to 3,200 m in altitude. Fourteen species were recorded, 12 of which were positive for Bd. A total of 541 individuals were diagnosed and 100 were positive. Our analyses showed that preserved areas play an important role in keeping many individuals Bd–free as compared to those in degraded areas. This was the first study to evaluate diversity and infection by Bd in the northeast region of Colombia. Our findings may help improve our knowledge of the diversity of amphibian species in the area and facilitate the implementation of action plans to mitigate the causes associated with the decrease in amphibian populations. (Author)

A Qualitative Case Study to Investigate the Technology Acceptance Experience Outlined in the TAM Using the Kubler-Ross Stages of Grieving and Acceptance

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Sotelo, Benjamin Eladio

2015-01-01

The Technology Acceptance Model (TAM) has been an important model for the understanding of end user acceptance regarding technology and a framework used in thousands of researched scenarios since publication in 1986. Similarly, the Kubler-Ross model of death and dying has also been used as a model for the study of acceptance within the medical…

Diversity of resource use and property rights in Tam Giang Lagoon, Vietnam

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Ta Thi Thanh Huong

2011-02-01

Full Text Available Since the early 1990s, aquaculture has become the most important livelihood activity in Tam Giang Lagoon, Vietnam. The aquaculture boom has reduced the available water area for mobile gear fishers, polarized different user-groups, created resource conflicts, and increased pressures on the lagoon systems. Aquaculture in the lagoon is governed by both customary and legal rights. The objective of this paper is to explore the diversity of resource use and the complexity of property rights in one of the villages located in the lagoon. The paper emphasizes the linkages between changes in commons institutions and changes in resource use and property rights. First, the political and socio-economic changes in Vietnam are examined as well as how they have influenced traditional commons institutions and lagoon resource management in the village. Second, the linkages between common institutions and the diversity of property rights are analyzed. Particular attention is given to the analysis of different types of resource use associated with "bundle of rights" and the diversity of property rights regimes in the village.

The Influence On Factors In Attitudes Toward Acceptance Of The Information System Using Technology Acceptance Model TAM Case Study SPAN System In Indonesia

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Donny Maha Putra

2015-08-01

Full Text Available Theoretically and practically Technology Acceptance Model TAM is a model that is considered most appropriate in explaining how the user receives a system. This study aimed to analyze the factors that influence the attitudes towards the acceptance of Sistem Perbendaharaan Anggaran Negara SPAN using TAM approach. The problems raised in this research aims to determine the attitude of the use of the transition process lagecy system to the new system which for many users create conflict in the process of adaptation. On the basis of this proposed theoretical models to test hypotheses using Structural Equation Model SEM and analysis tool using lisrel. This research was conducted in all offices DG of Treasury of Ministry of Finance with 210 respondents were chosen at random to represent each office. The results of this study prove 4 hypothesis is accepted from 8 hypothesis namely a a negative affect with the results demonstrabilty b computer self-efficacy with the output quality c computer self-efficacy with the perceived ease of use d perceived ease of use with the perceived of usefulness. Overall indicates that the application of the SPAN system in the Ministry of Finance of In Indonesia can be accepted by users.

Exploring Lecturers' Perceptions of Learning Management System: An Empirical Study Based on TAM

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Wei Wei Goh

2014-06-01

Full Text Available With the pervasive take-up and presence of digital technologies, learning management system (LMS is popular for its open accessibility and its interactive nature. Implementation of LMS has become part of the strategic plan in higher education institution to enhance the flexibility in teaching and learning. It is essential to explore the perceptions of users in using the LMS in order to inform stakeholders the positive influencing aspects and improve the negative factors in the future. This study investigates the perception of lecturers in using LMS in term of perceived usefulness and perceived ease of use for teaching purposes. Technology Acceptance Model (TAM is used as the research framework to design the questionnaire. An online questionnaire was created to address the research questions. The results reveal that lecturers do not react positively towards perceived ease of use of Moodle for teaching. Lecturers treat Moodle as content repository and do not fully utilize the interactive features in Moodle. It was found that usability issues, interaction and communication issues had a negative impact on the lecturers' perception.

The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in Resource-Limited Settings.

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Campbell, Jeffrey I; Aturinda, Isaac; Mwesigwa, Evans; Burns, Bridget; Santorino, Data; Haberer, Jessica E; Bangsberg, David R; Holden, Richard J; Ware, Norma C; Siedner, Mark J

2017-11-01

Although mobile health (mHealth) technologies have shown promise in improving clinical care in resource-limited settings (RLS), they are infrequently brought to scale. One limitation to the success of many mHealth interventions is inattention to end-user acceptability, which is an important predictor of technology adoption. We conducted in-depth interviews with 43 people living with HIV in rural Uganda who had participated in a clinical trial of a short messaging system (SMS)-based intervention designed to prompt return to clinic after an abnormal laboratory test. Interviews focused on established features of technology acceptance models, including perceived ease of use and perceived usefulness, and included open-ended questions to gain insight into unexplored issues related to the intervention's acceptability. We used conventional (inductive) and direct content analysis to derive categories describing use behaviors and acceptability. Interviews guided development of a proposed conceptual framework, the technology acceptance model for resource-limited settings (TAM-RLS). This framework incorporates both classic technology acceptance model categories as well as novel factors affecting use in this setting. Participants described how SMS message language, phone characteristics, and experience with similar technologies contributed to the system's ease of use. Perceived usefulness was shaped by the perception that the system led to augmented HIV care services and improved access to social support from family and colleagues. Emergent themes specifically related to mHealth acceptance among PLWH in Uganda included (1) the importance of confidentiality, disclosure, and stigma, and (2) the barriers and facilitators downstream from the intervention that impacted achievement of the system's target outcome. The TAM-RLS is a proposed model of mHealth technology acceptance based upon end-user experiences in rural Uganda. Although the proposed model requires validation, the TAM

The expression of inflammatory cytokines, TAM tyrosine kinase receptors and their ligands is upregulated in venous leg ulcer patients: a novel insight into chronic wound immunity.

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Filkor, Kata; Németh, Tibor; Nagy, István; Kondorosi, Éva; Urbán, Edit; Kemény, Lajos; Szolnoky, Győző

2016-08-01

The systemic host defence mechanisms, especially innate immunity, in venous leg ulcer patients are poorly investigated. The aim of the current study was to measure Candida albicans killing activity and gene expressions of pro- and anti-inflammatory cytokines and innate immune response regulators, TAM receptors and ligands of peripheral blood mononuclear cells separated from 69 venous leg ulcer patients and 42 control probands. Leg ulcer patients were stratified into responder and non-responder groups on the basis of wound healing properties. No statistical differences were found in Candida killing among controls, responders and non-responders. Circulating blood mononuclear cells of patients overexpress pro-inflammatory (IL-1α, TNFα, CXCL-8) and anti-inflammatory (IL-10) cytokines as well as TAM receptors (Tyro, Axl, MerTK) and their ligands Gas6 and Protein S compared with those of control individuals. IL-1α is notably overexpressed in venous leg ulcer treatment non-responders; in contrast, Axl gene expression is robustly stronger among responders. These markers may be considered as candidates for the prediction of treatment response among venous leg ulcer patients. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

An Exploration of Social Networking Sites (SNS) Adoption in Malaysia Using Technology Acceptance Model (TAM), Theory of Planned Behavior (TPB) And Intrinsic Motivation

OpenAIRE

Goh Say Leng; Suddin Lada; Mohd Zulkifli Muhammad; Ag Asri Hj Ag Ibrahim; Tamrin Amboala

2011-01-01

The objective of the paper is to explore the factors that encourage students to adopt social network sites (SNS) in Malaysia and to use the study’s findings to develop guidelines for SNS providers on how to maximize the rate of adoption. A conceptual model of Technology Acceptance Model (TAM), Theory of Planned Behaviour (TPB) and intrinsic motivation is proposed and empirically tested in the context of SNS usage. Structural Equation modelling was used on the survey data from 283 university s...

Extending TAM and IDT to Predict the Adoption of the Internet for B-to-B Marketing Activities: An Empirical Study of UK Companies

OpenAIRE

Riyad Eid

2009-01-01

There has been considerable Research into the usage of the Internet for Business-to-Business (B-to-B) marketing activities in recent years. The need to understand how and why B-to-B companies utilize the Internet is important for researchers and practitioners alike. This study combines Davis’ model-the Technology Acceptance Model (TAM)- and Roger’s Theory- the Innovation diffusion Theory (IDT) to understand the process of Internet adoption for marketing purposes. It makes a comprehensive ...

The Development of a Competency Testing Systems: Adopting TAM to Explore User’s Acceptance

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Ibrahim Wahyu Saputra

2017-12-01

Full Text Available The main problems of learning evaluation using paper based-test are inefficient time and cost. Technology can be used as a system to evaluate the learning process. Using technology can save time and cost of implementing learning evaluations. The aims of this study are to create a software product that can be used to evaluate the learning process. This software product is designed to be used by the test organizer or test committee, the teachers and the students (test takers. This software product was developed using Waterfall Model with five stages of development; communication, planning, modeling, construction, and deployment. The testing was conducted by using Blackbox Method and TAM Theory by considering the aspect of usefulness and the aspect ease of use. The analysis was based on the flow of the current test system. The web-based platform enables ease of access for conducting work in various places. According to the result, the Developed Skills Competency Test System is accepted and can be used by the user as an evaluation system.

Forecasting Areas Vulnerable to Forest Conversion in the Tam Dao National Park Region, Vietnam

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Duong Dang Khoi

2010-04-01

Full Text Available Tam Dao National Park (TDNP is a remaining primary forest that supports some of the highest levels of biodiversity in Vietnam. Forest conversion due to illegal logging and agricultural expansion is a major problem that is hampering biodiversity conservation efforts in the TDNP region. Yet, areas vulnerable to forest conversion are unknown. In this paper, we predicted areas vulnerable to forest changes in the TDNP region using multi-temporal remote sensing data and a multi-layer perceptron neural network (MLPNN with a Markov chain model (MLPNN-M. The MLPNN-M model predicted increasing pressure in the remaining primary forest within the park as well as on the secondary forest in the surrounding areas. The primary forest is predicted to decrease from 18.03% in 2007 to 15.10% in 2014 and 12.66% in 2021. Our results can be used to prioritize locations for future biodiversity conservation and forest management efforts. The combined use of remote sensing and spatial modeling techniques provides an effective tool for monitoring the remaining forests in the TDNP region.

EVALUASI PENERIMAAN PENGGUNA COMPUTER BASED TEST DENGAN PENDEKATAN TAM DI KULON PROGO

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Sukasna .

2017-02-01

Implementation of national examinations in junior high, high school / vocational equivalent is implemented by the Ministry ofEducation and Culture of the Republic of Indonesia is always changing, both in terms of benefits, technical implementation, thenumber of package models matter up with ways of correcting the results of the exam. Along with the technological development ofnational examinations now begin to be implemented by means of a computer on-line or better known as Computer Based Test (CBT.The purpose of this study was to examine the effect: the experience of the perception of usefulness and ease; complexity to theperception of usefulness and ease; the suitability of tasks to perception of usefulness and ease; perceived ease the perception ofusefulness; perceptions of the usefulness of the attitude of users; perceived ease of the attitude of users; perceptions of the usefulnessof the behavior of interest; user attitude towards the behavior of interest; behavior towards the use of real interest in the use of CBT.The approach used in this study is the Technology Acceptance Model (TAM I think Davis (1989 with SEM method PLS program totest the hypothesis in this study using SEM Based Component Analysis or Partial Least Square (PLS. The results obtained from thisstudy finding significant influence and no significant external variables as well as some of the perceptions that influence theimplementation of CBT in Kulon Progo.

Csapody, Tamás. 2014. Bortól Szombathelyig - Tanulmányok a bori munkaszolgálatról és a bori munkaszolgálatosok részleges névlistája ('From Bor to Szombathely- Studies on the Forced Labor Service at Bor Camp and the Partial List of the Forced Laborers in Bor'. Budapest: Zrinyi Kadó. 254 pp. ; Csapody, Tamás. 2015. A Cservenkai tömeggyilkosság ('The Mass Murder at Cservenka'. Budapest: Zsidó Tudományok Szabadegyeteme Alapítvány. 150 pp.

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Julia Bock

2016-10-01

Full Text Available Csapody, Tamás. 2014. Bortól Szombathelyig - Tanulmányok a bori munkaszolgálatról és a bori munkaszolgálatosok részleges névlistája ('From Bor to Szombathely- Studies on the Forced Labor Service at Bor Camp and the Partial List of the Forced Laborers in Bor'. Budapest: Zrinyi Kadó. 254 pp. ; Csapody, Tamás. 2015. A Cservenkai tömeggyilkosság ('The Mass Murder at Cservenka'. Budapest: Zsidó Tudományok Szabadegyeteme Alapítvány. 150 pp. (e-book; a shorter version is accessible at: http://zsido.com/konyvek/a-cservenkai-tomeggyilkossag/.

A Rentabilidade da TAM no Contexto de Elevação do Preço do Barril de Petróleo

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Antônio Nunes Pereira

2008-01-01

Full Text Available The present study aims at evaluating the extent to which the international increase in petroleum price per barrel impacted the profitability of the Transportes Aéreos Marília S.A. (TAM airlines. The context of civil aviation is explored in the case study methodology, including DuPont Method and simple linear regression for the 2001-2006 period. The study attempts to falsify the hypothesis of no relationship between the increase in petroleum price per barrel and profitability. Apparently, the price of a barrel of petroleum influences TAM¿s ROA, ROE, Cost of Assets and Services, Operational Budget, and Net Profit, especially on quarterly bases (significance level: p < .05.

DAİRESEL DALGA KILAVUZLARININ OPTİMİZE EDİLMİŞ İLETİM HATTI MATRİS MODELİ İLE TAM DALGA ANALİZİ

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Ayhan AKBAL

2013-05-01

Full Text Available Düşük firekaslarda kullanılan yaklaşımlar yüksek frekanslarda geçerli olmadığında analizde tam-dalga yöntemlerinin kullanılması bir zorunluluktur. İletim Hattı Matrisi Modeli (TLM bir tam-dalga analiz yöntemi olup literatürde elektromanyetik olayların analizinde sıklıkla kullanılmaktadır. Ancak bu modelde sınır şartlarından kaynaklanan yansıma, aşma, üst üste binme, bozulma, sinyal bütünlüğünün bozulması gibi çeşitli problemler ile karşılaşılmaktadır. Bu çalışmada TLM yönteminde sınır şartlarının kolay uygulanabilmesi için optimizasyon yapılmıştır. Optimizasyonun başarısını göstermek içinde örnek olarak analizi daha komplex olan dairesel dalga klavusu kullanılmıştır. Bu yayında X bandında (8-12 GHz kullanılan WC-94 adlı dairesel dalga kılavuzu TE ve TM modu için ayrı ayrı, optimize edilmiş TLM yöntemi ile analiz edilmiştir. Sonuçların doğrulugu ve sunulan optimizasyon yönteminin başarısı ayrıntıları ile sunulmuştur.

Analisi terminologica dei siti web delle Compagnie Aeree British Airways, Alitalia, Tam e LAN

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Claudia Maria Astorino

2012-02-01

Full Text Available This study is part of a research about the terminology found in the language of tourism, defined as an area of ??knowledge. It has been conducted a study based upon the terms used by four major international airlines - two from Europe: British Airways (United Kingdom and Alitalia (Italy, and two from Latin America: TAM (Brazil and Lan (Chile - in their websites, designed for the final consumer (passenger, since each of them has a different official language (English, Italian, Portuguese and Spanish, respectively. The specific objectives were: i to reflect about the differences among the terms used by each airline, ii to analyze whether there is a substantial presence of acronyms, iii to identify how each of these airlines use English, considering that only the first one has it as its official language. The hypothesis that have guided the research are: i there are no significant changes among the terminology used by the airlines which are the object of the present research, ii, there is a fair use of synonyms for the same concepts, iii there is an extensive use of acronyms, iv there is a considerable influence of English, that may be seen in language borrowings and in some hybrid formations.

Juros sobre capital próprio: um estudo da economia tributária nas empresas Gol e Tam

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Sérgio Murilo Petri

2013-11-01

Full Text Available Esta pesquisa tem como objetivo evidenciar a economia tributária obtida pelas empresas de transporte aéreo GOL e TAM por meio da utilização dos juros sobre capital próprio como remuneração ao acionista. Para isso, foi realizada uma pesquisa descritiva das empresas de transporte aéreo listadas na BM&FBOVESPA. Para a condução do estudo, foi realizada uma pesquisa documental de caráter quantitativo e qualitativo. Pelos resultados obtidos, pôde-se perceber que a remuneração aos acionistas por meio dos juros sobre capital próprio resultou em uma economia tributária de aproximadamente R$ 112,7 milhões nas duas empresas analisadas entre 2006 e 2010. Além disso, ficou evidenciado que as empresas de transporte aéreo analisadas têm adotado a prática de remuneração utilizando os juros sobre capital próprio, havendo a GOL, em 2009 e 2010, e a TAM, em 2010, optado por remunerar seus acionistas apenas por meio de dividendos obrigatórios, não ficando evidenciado em notas explicativas o motivo da decisão. Então, analisando o quadro societário e utilizando a distribuição dos JSCPs somente para as pessoas jurídicas, as empresas teriam economizado ainda R$ 56,906 milhões; distribuindo para as pessoas físicas sobre forma de dividendos por ser mais viável ao acionista, uma vez que não teriam o desconto de 15% do IR retido na fonte (pagando imposto de renda na pessoa física. Conclui-se, então, que o benefício fiscal dos JSCPs é relevante para as empresas, tendo em vista a economia tributária auferida com a utilização de tal benefício Fiscal do ente tributante. Entretanto, a empresa deve levar em consideração se o acionista é pessoa física (PF ou jurídica (PJ, pois para as PFs não é interessante a distribuição mediante os JSCPs uma vez que estes têm retenção de 15% de IR e com os dividendos não teriam de pagar imposto de renda na pessoa física.  

Juros sobre capital próprio: um estudo da economia tributária nas empresas Gol e Tam

Directory of Open Access Journals (Sweden)

Sérgio Murilo Petri

2013-07-01

Full Text Available Esta pesquisa tem como objetivo evidenciar a economia tributária obtida pelas empresas de transporte aéreo GOL e TAM por meio da utilização dos juros sobre capital próprio como remuneração ao acionista. Para isso, foi realizada uma pesquisa descritiva das empresas de transporte aéreo listadas na BM&FBOVESPA. Para a condução do estudo, foi realizada uma pesquisa documental de caráter quantitativo e qualitativo. Pelos resultados obtidos, pôde-se perceber que a remuneração aos acionistas por meio dos juros sobre capital próprio resultou em uma economia tributária de aproximadamente R$ 112,7 milhões nas duas empresas analisadas entre 2006 e 2010. Além disso, ficou evidenciado que as empresas de transporte aéreo analisadas têm adotado a prática de remuneração utilizando os juros sobre capital próprio, havendo a GOL, em 2009 e 2010, e a TAM, em 2010, optado por remunerar seus acionistas apenas por meio de dividendos obrigatórios, não ficando evidenciado em notas explicativas o motivo da decisão. Então, analisando o quadro societário e utilizando a distribuição dos JSCPs somente para as pessoas jurídicas, as empresas teriam economizado ainda R$ 56,906 milhões; distribuindo para as pessoas físicas sobre forma de dividendos por ser mais viável ao acionista, uma vez que não teriam o desconto de 15% do IR retido na fonte (pagando imposto de renda na pessoa física. Conclui-se, então, que o benefício fiscal dos JSCPs é relevante para as empresas, tendo em vista a economia tributária auferida com a utilização de tal benefício Fiscal do ente tributante. Entretanto, a empresa deve levar em consideração se o acionista é pessoa física (PF ou jurídica (PJ, pois para as PFs não é interessante a distribuição mediante os JSCPs uma vez que estes têm retenção de 15% de IR e com os dividendos não teriam de pagar imposto de renda na pessoa física.

Promiscuity and selectivity of small-molecule inhibitors across TAM receptor tyrosine kinases in pediatric leukemia.

Science.gov (United States)

Liu, Mao-Hua; Chen, Shi-Bing; Yu, Juan; Liu, Cheng-Jun; Zhang, Xiao-Jing

2017-08-01

The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3. The location and conformation of active-site residues of Mer and Axl are highly consistent, suggesting that small-molecule inhibitors generally have a low Mer-over-Axl selectivity and a high Mer-over-Tyro3 selectivity. We demonstrated that the difference in ATP binding potency to the three kinases is also responsible for inhibitor selectivity. We also found that the long-range interactions and allosteric effect arising from rest of the kinase's active site can indirectly influence inhibitor binding and selectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of the pine processionary moth on the increment of ...

African Journals Online (AJOL)

STORAGESEVER

2009-05-18

May 18, 2009 ... sycophanta L. (Coleoptera: Carabidae) used against the pine processionary moth (Thaumetopoea pityocampa Den. & Schiff.) (Lepidoptera: Thaumetopoeidae) in biological control. T. J. Zool. 30:181-185. Kanat M, Sivrikaya F (2005). Effect of the pine processionary moth on diameter increment of Calabrian ...

THE USE OF INFORMATION COMMUNICATION TECHNOLOGY (ICT AS THE TECHNOLOGY ACCEPTANCE MODEL (TAM OF MOBILE BANKING

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Paulus Yokie Radnan

2018-01-01

Full Text Available Information Technology services in banking business which is very dynamic and advanced makes the bankers must adjust to the presence of this technology. In this paper, the authors will explain the role of Mobile banking technology which is provided by CIMB Niaga in servicing its customers for banking transactions. The methodology used in this paper is quantitative with the purposive sampling one. Instrument used the Technology Acceptance Model (TAM as developed by Parasuraman and Davis by modifying them to fit the state of the research object. This research was conducted in Jakarta and several other places. Research and data collection took 6 months from November 2015 to April 2016. The variables included trust, perceived use (PU, perceived ease of use (PEU, attitude toward use (ATU, Intent to use (ITU, and actual use (AU. After the data were collected, the regression analysis was performed. From the analysis result it was found that trust and perceived use (PU variables did not positively and significantly influence the intent to use (ITU variable, as well as the perceived use variables (PU and perceived ease of use (PEU which have no significant and positive effect on attitude variable on usage (ATU. For that case, the authors propose an improvement strategy to maintain and grow this business forward.

Exploring the role of ethnic media and the community readiness to combat stigma attached to mental illness among Vietnamese immigrants: the pilot project Tam An (Inner Peace in Vietnamese).

Science.gov (United States)

Han, Meekyung; Cao, Lien; Anton, Karen

2015-01-01

Vietnamese Americans are at high risk for developing mental health disorders due to multiple risk factors such as trauma and acculturative stress. However, the utilization of mental health services has been low. The pilot project Tam An was implemented to raise mental health awareness by engaging community resources in the Vietnamese population. Informed by the Community Readiness Model and through local ethnic media sources, messages to destigmatize mental health and promote the willingness to initiate mental health treatment were presented. Using an exploratory perspective, findings from focus group data suggest that the project improved the community's stage of readiness.

Consumers' acceptance of medicinal herbs: An application of the technology acceptance model (TAM).

Science.gov (United States)

Jokar, Nargesh Khatun; Noorhosseini, Seyyed Ali; Allahyari, Mohammad Sadegh; Damalas, Christos A

2017-07-31

The shift in consumers' preferences from synthetic to 'natural' products has led to a resurgence of interest in medicinal plants, particularly in developing countries. However, research data about consumers' preferences for particular products is hard to find. The main objective of this study was to contribute to the general understanding of consumers' intention for selecting medicinal herbs for consumption. Factors underpinning consumers' acceptance of medicinal herbs were studied with the technology acceptance model (TAM) in Rasht City of Iran using a structured questionnaire. Most respondents had low to moderate familiarity with consumption of medicinal herbs. However, about half of the respondents (47.5%) showed a high level of acceptance of medicinal herbs. Herbs like spearmint (Mentha spicata L.), spinach (Spinacia oleracea L.), basil (Ocimum basilicum L.), Damask rose (Rosa × damascena Herrm.), saffron (Crocus sativus L.), cinnamon (Cinnamomum verum J.Presl), flixweed [Descurainia sophia (L.) Webb ex Prantl], red feathers (Echium amoenum Fisch. & C.A.Mey.), and green tea [Camellia sinensis (L.) Kuntze] had the highest consumption rate among the majority (over 75%) of citizens of Rasht. The highest rate of perceived usefulness of medicinal herbs was related to their perceived role in healing diseases. The variable of importance of use of medicinal herbs had the strongest direct effect and the variables of perceived usefulness and attitude towards use had the second and third strongest direct effect on the acceptance of medicinal herbs' use at p acceptance of medicinal herbs and may serve as a benchmark for future research and evaluation concerning the use of medicinal herbs over time. For plant producers, more effective and targeted crop development should be encouraged, whereas for retailers better marketing and delivery strategies should be sought. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

FAKTOR PENENTU MINAT PENGGUNAAN INSTAGRAM UNTUK PEMBELIAN ONLINE MENGGUNAKAN TECHNOLOGY ACCEPTANCE MODEL (TAM DAN THEORY OF PLANNED BEHAVIOR (TPB

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Bayu Indrayana

2016-05-01

Full Text Available The objective of this research is to examine the factors that determine the interest in using Instagram in making online purchases. This study also analyzes the pattern of attitude relationship, subjective norms, behavioral control, and uses on interest in using Instagram for online purchases. In addition, the purpose of the research is to analyze whether there are contributions of usability and convenience toward the attitudes and easiness in using the Instagram toward the usage. Data analysis tool used is the structural equation modeling (SEM which is based technology acceptance model (TAM and theory of planned behavior (TPB. The results showed that subjective norms significantly influence the interest in using Instagram for online purchases; however, behavior control factors, usability and attitude are not significantly influential. Attitude is a factor that has the greatest influence among other factors. Instagram users from companies/businesses that intend to make use of Instagram as their digital marketing media need to pay attention to aspects of attitudes, subjective norms, behavioral control and usability.Key words: model of technology acceptance, consumer behavior, Structural Equation Modelling (SEM, social media

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

International Nuclear Information System (INIS)

Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

1995-01-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

Energy Technology Data Exchange (ETDEWEB)

Fowble, B; Fein, D A; Hanlon, A L; Eisenberg, B L; Hoffman, J P; Sigurdson, E R; Daly, M B; Goldstein, L J

1995-07-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

Mobile Tourism Guide in the Context of Thai National Parks: The Effects of Mobile Design Qualities in TAM2

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Trakulmaykee Numtip

2014-01-01

Full Text Available This study aims to predict the level of international tourists’ intention to use MTG in the context of Thai national parks, and investigates the roles of mobile design qualities (content quality, appearance quality, and interaction quality through perceived usefulness and perceived ease-of-use on intention. The mixed-method via exploratory sequential design is conducted this study. The qualitative approach is started in the first stage then quantitative approach is employed to analyze the large sample size. This study extends the TAM2 with mobile design qualities. The results shows the high level of international tourist’ intention to use MTG. It indicates that the international tourists will intent to the mobile tourism guide (MTG, if the MTG is provided for them. The direct factors of tourists’ intention are perceived usefulness, perceived ease-of-use, mobile content quality and mobile appearance quality. The most direct effect is mobile content quality. The qualities of content and appearance have the positive roles on perceived usefulness, while the qualities of appearance and interaction have the indirect effects through perceived ease-of-use on tourists’ intention. The proposed model provides the body of knowledge in the context of MTG, especially the factors of international tourists’ intention to use MTG.

Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells.

Science.gov (United States)

Kim, Sangmin; Lee, Jeongmin; Oh, Soo Jin; Nam, Seok Jin; Lee, Jeong Eon

2015-09-01

Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.

Effects of vibration on stone pine trees (Pinus pinea L.) on the vigor of the trees: crown density, growth shoots and parasites of weak trees.; Efectos del vibrado del pino pinonero (Pinus pinea L.) en el vigor de los arboles: densidad de copa, crecimiento de guias y parasitos de debilidad

Energy Technology Data Exchange (ETDEWEB)

Martinez-Zurimendi, P.; Alvarez, J. M.; Pando, V.; Dominguez, M.; Gordo, J.; Finat, L.; Sierra-De-Grado, R.

2009-07-01

In the northwest of Spain the mechanized harvesting of pine cones is more and more frequent. In order to quantify the effects of vibration on the vigor of the trees, parcels of stone pine were planted in plateau and countryside. Both the mechanized and manual harvests were analyzed in adult and young trees. The growth of the tree shoots was measured. The presence and abundance of three insect plagues was analyzed in those same trees: Tacoma's piniperda, Rhyacionia buoliana and Thaumetopoea pityocampa. The average shoot length of those trees manually harvested was superior to that of those mechanically harvested. The difference was very significant in young trees (40-50 years old) in the countryside and in adult trees (more than 80 years) on the plateau. Rhyacionia buoliana was more abundant in adult trees that young trees, but the relation of its abundance with the harvest method was not seen. The presence of Tomicus piniperda was rare and was only detected in mechanically harvested stands. Thaumetopoea pityocampa was more frequent in trees harvested by hand than those harvested mechanically and was more abundant in young stands. The percentage tree of defoliation was low in all stands independent of harvest method. (Author) 45 refs.

CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

International Nuclear Information System (INIS)

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

2013-01-01

Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

Energy Technology Data Exchange (ETDEWEB)

Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

2013-11-15

Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

Marketing digital e de relacionamento: Avaliação de um sistema de informação digital usando uma integração da TAM, TTF e modelos KMV

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Plínio Rafael Reis Monteiro

2017-01-01

Full Text Available A ascendente popularidade da internet prolifera formas de entretenimento, comunicação e trabalho, tais como os portais, que visam difundir informações e fomentar relacionamentos entre stakeholders. Este estudo buscou verificar como a interação tecnológica do portal de uma IES afeta atitudes (satisfação, confiança e comprometimento e intenções comportamentais (utilização do portal, lealdade e comunicação positiva dos discentes. A partir de um survey concebido pelos modelos TAM, TTF e KMV o estudo evidencia que as características e a adequação da tecnologia influenciam na utilidade percebida no portal e nas atitudes moderadoras de intenções comportamentais para a instituição estudada.

Impacto da contabilização do leasing operacional no balanço patrimonial: o caso das Cias. aéreas brasileiras TAM e GOL = The impact of operating leasing recognition in the balance sheet: the case of brazilian airlines companies Tam and Gol

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Ludmila de Melo Souza

2011-08-01

Full Text Available As operações de leasing são utilizadas pelas empresas como uma forma alternativa de capitalização. Atualmente, esse tipo de operação pode ser classificado em duas modalidades: financeiro e operacional, em que este funciona como um contrato de aluguel e aquele se assemelha a uma compra financiada. Em termos de contabilização, a grande diferença é que o leasing operacional não integra o balanço. O FASB, ciente dessa possível distorção que a não contabilização gera no usuário da informação contábil, reuniu-se com o IASB e discutiram a melhor forma para solucionar o problema. Os dois conselhos decidiram provisoriamente que as arrendatárias devem contabilizar as operações decorrentes de leasing operacional no ativo e no passivo. Portanto, o objetivo do trabalho é verificar o impacto da contabilização do leasing operacional de forma semelhante ao leasing financeiro na estrutura patrimonial das empresas presentes na amostra. Assim, o presente trabalho analisou os Balanços Patrimoniais da TAM e da GOL nos anos de 2007 a 2009, uma vez que as companhias aéreas são grandes usuárias das operações de leasing operacional na “aquisição” de aeronaves. Os balanços foram ajustados com os valores informados nas notas explicativas. Conclui-se que o registro das operações de leasing operacional representou para as empresas analisadas um significativo impacto na estrutura patrimonial e consequentemente nos indicadores financeiros e que a contabilização das operações de leasing operacional dará maior transparência às demonstrações contábeis.Leasing transactions are used by companies as a way to get capitalized. However, this type of transaction can be classified in two types: financial and operating, in which the operating leasing works as a rent and financial leasing resembles a financed purchase. The most important difference in the accounting model is that the operating lease is not included in the balance sheet

ANALISIS PENERIMAAN PENGGUNAAN OTOMASI PERPUSTAKAAN UNNES BERDASARKAN PENDEKATAN TECHNOLOGY ACCEPTANCE MODEL (TAM

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Mia Winda Anzaeni

2017-06-01

Full Text Available Otomasi Perpustakaan merupakan sistem informasi perpustakaan berbasis web di Universitas Negeri Semarang. Penelitian ini bertujuan untuk mengetahui pengaruh dan menganalisis faktor-faktor yang mempengaruhi penerimaan penggunaan Otomasi Perpustakaan. Pendekatan yang digunakan adalah Technology Acceotance Model (TAM. Populasi dalam penelitian ini adalah mahasiswa pendidikan akuntansi di Universitas Negeri Semarang. Jumlah sampel sebanyak 127 responden. Teknik pengambilan sampel menggunakan non probablity sampling dengan sampling kuota. Metode pengumpulan data menggunakan kuesiioner. Data dianalisis menggunakan teknik path analysis. Hasil penelitian menunjukkan bahwa ada pengaruh positif dan signifikan manfaat (PU terhadap penerimaan (ACC sebesar 24,5%, kemudahan (PEOU terhadap ACC sebesar 24,8%, ATU terhadap ACC sebesar 40,7%, PU terhadap ATU sebesar 25,1%, PEOU terhadap ATU sebesar 24,5%, PU melalui ATU terhadap ACC sebesar 10,2% dan PEOU melalui ATU terhadap ACC sebesar 10%. Berdasarkan penelitian, dapat disimpulkan bahwa terdapat pengaruh perceived usefulness dan perceived ease of use terhadap acceptance baik secara langsung maupun tidak langsung dan pengarung langsung attitude terhadap acceptance. Disarankan kepada pengelola website Otomasi Perpustakaan agar dapat meningkatkan fungsi dari web sehingga pengguna dapat merasakan manfaat dan kemudahan web. Disarankan juga kepada peneliti selanjutnya untuk meneliti dengan objek yang berbeda, serta menambahkan variabel eksternal yang sesuai dengan penelitiannya. Library Automation is a web-based library information systems at the State University of Semarang. This study aims to determine the effect and analyze the factors that affect the acceptance of the use of Library Automation. The population in this research were students of accounting education at State University of Semarang. The total sample of 127 respondents. The sampling technique used is non-probability sampling with quota sampling

75 FR 36516 - Addition and Removal of Certain Persons on the Entity List: Addition of Persons Acting Contrary...

Science.gov (United States)

2010-06-28

... reasons. OnTime Electronics Technology Company and Tam Wai Tak, a.k.a., Thomsom Tam, are being added due... June 5, 2008, OnTime Electronics Technology Company and Tam Wai Tak were indicted in the Southern... Commercial Center, 28 Ferry Street, Jordon, Kowloon, Hong Kong; and (2) Tam Wai Tak, a.k.a., Thomsom Tam...

CB1 and CB2 Receptors are Novel Molecular Targets for Tamoxifen and 4OH-Tamoxifen

OpenAIRE

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

2013-01-01

Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for t...

Novel Shape-Stabilized Phase Change Materials Composed of Polyethylene Glycol/Nonsurfactant-Templated Mesoporous Silica: Preparation and Thermal Properties

Science.gov (United States)

Chen, Yan; Zhu, Yingying; Wang, Jinbao; Lv, Mengjiao; Zhang, Xiongjie; Gao, Junkai; Zhang, Zijun; Lei, Hao

2017-12-01

A novel shape-stabilized phase change material (PEG/TAMS), fabricated using tannic acid-templated mesoporous silica (TAMS) as a support for polyethylene glycol, was developed for thermal energy storage. The method used to synthesize TAMS was simple, cost effective, environmentally friendly, and free of surfactant. The characterization results indicated that PEG was physically absorbed to TAMS and that TAMS had no influence on the crystal structure of PEG. According to the TGA thermograms, PEG/TAMS has excellent thermal stability and can be applied over a wide temperature range. Additionally, the differential scanning calorimetry results suggested that PEG/TAMS has good thermal properties and that its fusion and solidification enthalpies reached 114.7 J/g and 102.4 J/g, respectively. The results indicated that PEG/TAMS has great potential for practical applications.

Delineation of Suitable Cropland Areas Using a GIS Based Multi-Criteria Evaluation Approach in the Tam Dao National Park Region, Vietnam

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Duong Dang Khoi

2010-07-01

Full Text Available Land degradation is recognized as one of the major threats to the buffer zones of protected areas (PAs in Vietnam. In particular, the expansion of land degradation into the PAs is exerting pressure on biodiversity conservation efforts. This degradation is partially the result of mismanagement: the utilization of the land is often unmatched with the inherent suitability of the land. Identification of the spatial distribution of suitable areas for cropland is essential for sustainable land-use recommendation. This paper aims to delineate the areas suitable for cropland in the Tam Dao National Park (TDNP region using a GIS-based multi-criteria evaluation of biophysical factors and Landsat ETM+ imagery. GIS is used to generate the factors, while MCE is used to aggregate them into a land suitability index. The results indicate the location and extent of crop farming areas at different suitability levels, i.e., most suitable (28.10%, moderately suitable (23.96%, marginally suitable (28.77%, and least suitable (19.17%. The current cropland covers 46.5% of the study area, while most and moderately suitable areas are estimated to be 52.06% of the territory. The results can be used to identify priority areas for crop farming and sustainable land-use management. The GIS-MCE approach provides an effective assessment tool for land-use managers working in protected areas of Vietnam.

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

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Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

2018-05-28

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Tamoxifen for one year versus two years versus 6 months of Tamoxifen and 6 months of megestrol acetate: A randomized comparison in postmenopausal patients with high-risk breast cancer (DBCG 89C)

DEFF Research Database (Denmark)

Andersen, Jørn; Kamby, C.; Ejlertsen, B.

2008-01-01

From January 1, 1990 to December 31, 1994, DBCG conducted a randomised trial in 1 615 postmenopausal women with operable, high-risk, receptor-positive or -unknown breast cancer. The patients were after surgery randomised to Tamoxifen for 1 year (TAM1), Tamoxifen for 2 years (TAM 2) or Tamoxifen...... for 6 months followed by megestrol acetate for 6 months (TAM/MA). When the preplanned sample size of 1 500 patients was reached it was decided to continue randomisation to TAM1 or TAM2 and the study was finally closed December 31, 1996. With a median follow-up of more than 10 years...... in hazard ratios for DFS or OS among the three arms. Sideeffects were rare but more common in the TAM2 and TAM/MA arms Udgivelsesdato: 2008...

Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6

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Ke Geng

2017-11-01

Full Text Available The Tyro3, Axl, and Mertk (TAM receptors are homologous type I receptor tyrosine kinases that have critical functions in the clearance of apoptotic cells in multicellular organisms. TAMs are activated by their endogenous ligands, growth arrest-specific 6 (Gas6, and protein S (Pros1, that function as bridging molecules between externalized phosphatidylserine (PS on apoptotic cells and the TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote TAM activation remains elusive. Using TAM/IFNγR1 reporter cell lines to monitor functional TAM activity, we found that Gas6 activity was exquisitely dependent on vitamin K-mediated γ-carboxylation, whereby replacing vitamin K with anticoagulant warfarin, or by substituting glutamic acid residues involved in PS binding, completely abrogated Gas6 activity as a TAM ligand. Furthermore, using domain and point mutagenesis, Gas6 activity also required both an intact Gla domain and intact EGF-like domains, suggesting these domains function cooperatively in order to achieve TAM activation. Despite the requirement of γ-carboxylation and the functional Gla domain, non-γ-carboxylated Gas6 and Gla deletion/EGF-like domain deletion mutants still retained their ability to bind TAMs and acted as blocking decoy ligands. Finally, we found that distinct sources of PS-positive cells/vesicles (including apoptotic cells, calcium-induced stressed cells, and exosomes bound Gas6 and acted as cell-derived or exosome-derived ligands to activate TAMs. Taken together, our findings indicate that PS is indispensable for TAM activation by Gas6, and by inference, provides new perspectives on how PS, regulates TAM receptors and efferocytosis.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

Science.gov (United States)

Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

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Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

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Koni Ivanova

2018-03-01

Full Text Available BACKGROUND: Papillary thyroid carcinoma (PTC accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment. METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages. RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months compared to those with high CD68+ cells infiltration (p = 0.034. From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015. CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions.

Eficacia del difusor de feromona de procesionaria del pino Pherocon PPM®

OpenAIRE

Durán, María; Rodrigo Santamalia, Mª Eugenia; Pérez Laorga, Eduardo; Mas i Gisbert, Hugo

2012-01-01

Los resultados de este trabajo forman parte del trabajo de fin de carrera presentado en la Universidad Politecnica de Valencia por Maria Duran Lázaro y dirigido por la Dra. Eugenia Rodrigo Santamalia y Eduardo Perez Laorga con el titulo "Influencia del tipo de trampa en la captura de mariposas de la procesionaria del pino (Thaumetopoea pityocampa Schiff.) en la sierra Calderona" [ES] Se ha ensayado la eficacia de un difusor de la feromona de la procesionaria del pino fabricado por la em...

Climate change and forest plagues: the case of the pine

OpenAIRE

Seixas Arnaldo, P.; Oliveira, I.; Santos, J.; Leite, S.

2011-01-01

The pine processionary moth, Thaumetopoea pityocampa (Den. & Schiff.) (Lep., Thaumetopoeidae) is known as the most defoliating insect in Pinus and Cedrus in many countries. In the last three decades, climate change has led to a substantial expansion of its range and high attack rates in previously unaffected areas were observed. A 3-year analysis of the effect of several climatic elements on the T. pityocampa adult emergence was made and one climatic change scenario was tested in order to pre...

Celecoxib alleviates tamoxifen-instigated angiogenic effects by ROS-dependent VEGF/VEGFR2 autocrine signaling

International Nuclear Information System (INIS)

Kumar, B N Prashanth; Rajput, Shashi; Dey, Kaushik Kumar; Parekh, Aditya; Das, Subhasis; Mazumdar, Abhijit; Mandal, Mahitosh

2013-01-01

Tamoxifen (TAM) is widely used in the chemotherapy of breast cancer and as a preventive agent against recurrence after surgery. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy. Celecoxib (CXB), a selective COX-2 inhibitor, suppresses VEGF gene expression by targeting the VEGF promoter responsible for its inhibitory effect. For this study, we had selected CXB as non-steroidal anti-inflammatory drug in combination with TAM for suppressing VEGF expression and simultaneously reducing doses of both the drugs. The effects of CXB combined with TAM were examined in two human breast cancer cell lines in culture, MCF7 and MDA-MB-231. Assays of proliferation, apoptosis, angiogenesis, metastasis, cell cycle distribution, and receptor signaling were performed. Here, we elucidated how the combination of TAM and CXB at nontoxic doses exerts anti-angiogenic effects by specifically targeting VEGF/VEGFR2 autocrine signaling through ROS generation. At the molecular level, TAM-CXB suppresses VHL-mediated HIF-1α activation, responsible for expression of COX-2, MMP-2 and VEGF. Besides low VEGF levels, TAM-CXB also suppresses VEGFR2 expression, confirmed through quantifying secreted VEGF levels, luciferase and RT-PCR studies. Interestingly, we observed that TAM-CXB was effective in blocking VEGFR2 promoter induced expression and further 2 fold decrease in VEGF levels was observed in combination than TAM alone in both cell lines. Secondly, TAM-CXB regulated VEGFR2 inhibits Src expression, responsible for tumor progression and metastasis. FACS and in vivo enzymatic studies showed significant increase in the reactive oxygen species upon TAM-CXB treatment. Taken together, our experimental results indicate that this additive combination shows promising outcome in anti-metastatic and apoptotic studies. In a line, our preclinical studies evidenced that this additive

Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

DEFF Research Database (Denmark)

Sørensen, M D; Dahlrot, R H; Boldt, H B

2018-01-01

(+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold......AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

Science.gov (United States)

Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

2014-05-05

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings

DEFF Research Database (Denmark)

Cozzi-Lepri, Alessandro; Phillips, Andrew N; Martinez-Picado, Javier

2009-01-01

BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS...... until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95......% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual...

ANALISIS TEKNIK RAGAM DIALOG DIAGNOSIS PENYAKIT BERBASIS SPK DENGAN SEMPLS

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Jihadil Qudsi

2018-04-01

Full Text Available Decision support systems, commonly called DSS (or SPK in Bahasa, in medical used to diagnose illness. But within its implementation these systems are not used optimally. The main cause is the interface of the systems that is not accordance with the user wants. Three interface designs layouts were proposed for the phase of history and physical examination and two interface designs layouts for investigations to be assessed by the respondents. Based on the results of the questionnaires selected by respondents, statistical tests were performed to determine the value of the use of interface design based on the Technology Acceptance Model (TAM and modified TAM. The statistical methods used to examine the effect of variables on TAM and modified TAM i.e. the Structural Equation Modeling Partial Least Square (SEM PLS method. The results of this study indicate that the respondents’ choice in the TAM and modified TAM model for the history and physical examination is the same as the based filling system. While for the supporting stage there are differences of respondent choice on TAM model with choice of graphical interaction system and on modified TAM model with windowing system option.

Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors

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Chong Jiang MD

2017-01-01

Full Text Available Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs, but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM, a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7, and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

International Nuclear Information System (INIS)

Atanasov, Georgi; Hau, Hans-Michael; Dietel, Corinna; Benzing, Christian; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Matia, Ivan; Prager, Isabel; Schierle, Katrin; Robson, Simon C.; Reutzel-Selke, Anja; Pratschke, Johann; Schmelzle, Moritz; Jonas, Sven

2015-01-01

Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients’ survival. Statistical analysis was performed using SPSS software. Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6 % vs. 75.1 %; three-year 61.3 % vs. 42.4 %; both ρ < 0.05) and recurrence-free survival (one-year 93.9 % vs. 57.4 %; three-year 59.8 % vs. 26.2 %; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

Science.gov (United States)

Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2016-10-01

Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

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Argirović Aleksandar

2013-01-01

Full Text Available Background/Aim. It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH has been treated with a combination of tamsulosin (TAM + Serenoa repens (SR (TAM + SR. The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. Methods. In this prospective study patients had to have prostate volume (PV 3, a maximal flow rate (Qmax of 5-15 mL/s, with post voiding residual volume (PVR < 150 mL and serum prostatic antigen (PSA < 4 ng/mL. TAM (0.4 mg was administered once a day, SR (320 mg daily or SR (320 mg + TAM (0.4 mg daily for a median period of 6 months. Results. A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23% of the patients managed with TAM and 17 (21% with TAM + SR had drug-treated with related adverse reactions. No adverse effect was detected in the group SR. Conclusion. Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

Tumor-associated macrophage-derived IL-6 and IL-8 enhance invasive activity of LoVo cells induced by PRL-3 in a KCNN4 channel-dependent manner

International Nuclear Information System (INIS)

Xu, Heyang; Lai, Wei; Zhang, Yang; Liu, Lu; Luo, Xingxi; Zeng, Yujie; Wu, Heng; Lan, Qiusheng; Chu, Zhonghua

2014-01-01

Tumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca 2+ -activated K + (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α). However, whether TAMs participate in the progression and metastasis of CRC induced by PRL-3 remains unknown. We used flow cytometry, coculture, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, and immunofluorescence staining to determine the effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells. In this study, we found that TAMs facilitated the metastasis of CRC induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced. Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were also significantly increased. This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated through the NF-κB signal pathway, which is activated by TNF-α from CRC cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6 and IL-8 double positive cells in the stroma showed positive staining for the TAM marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of these cells correlated with higher clinical stage. Our findings suggested that TAMs participate in the

Application of TAM III to study sensitivity of soil organic matter degradation to temperature

Science.gov (United States)

Vikegard, Peter; Barros, Nieves; Piñeiro, Verónica

2014-05-01

Traditionally, studies of soil biodegradation are based on CO2 dissipation rates. CO2 is a product of aerobic degradation of labile organic substrates like carbohydrates. That limits the biodegradation concept to just one of the soil organic matter fractions. This feature is responsible for some problems to settle the concept of soil organic matter (SOM) recalcitrance and for controversial results defining sensitivity of SOM to temperature. SOM consists of highly complex macromolecules constituted by fractions with different chemical nature and redox state affecting the chemical nature of biodegradation processes. Biodegradation of fractions more reduced than carbohydrates take place through metabolic pathways that dissipate less CO2 than carbohydrate respiration, that may not dissipate CO2, or that even may uptake CO2. These compounds can be considered more recalcitrant and with lower turnover times than labile SOM just because they are degraded at lower CO2 rates that may be just a consequence of the metabolic path. Nevertheless, decomposition of every kind of organic substrate always releases heat. For this reason, the measurement of the heat rate by calorimetry yields a more realistic measurement of the biodegradation of the SOM continuum. TAM III is one of the most recent calorimeters designed for directly measuring in real time the heat rate associated with any degradation process. It is designed as a multichannel system allowing the concomitant measurement of to up 24 samples at isothermal conditions or through a temperature scanning mode from 18 to 100ºC, allowing the continous measure of any sample at controlled non-isothermal conditions. The temperature scanning mode was tested in several soil samples collected at different depths to study their sensitivity to temperature changes from 18 to 35 ºC calculating the Q10 and the activation energy (EA) by the Arrhenius equation. It was attempted to associate the obtained EA values with the soil thermal

NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

Science.gov (United States)

Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

2018-01-01

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

International Nuclear Information System (INIS)

Han, Peng; Kang, Jin-He; Li, Hua-Liang; Hu, Su-Xian; Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian; Li, Wen-Gang; Chen, Qing-Xi

2009-01-01

Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

Antiproliferation and apoptosis induced by tamoxifen in human bile duct carcinoma QBC939 cells via upregulated p53 expression

Energy Technology Data Exchange (ETDEWEB)

Han, Peng; Kang, Jin-He; Li, Hua-Liang [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Hu, Su-Xian [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Lian, Hui-Hui; Qiu, Ping-Ping; Zhang, Jian [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Li, Wen-Gang [First Hospital Attached to Fujian Medical University, Xiamen 361004 (China); Chen, Qing-Xi [Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005 (China); Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005 (China)

2009-07-24

Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been used in the treatment of breast cancer for over 30 years. Recently, it was shown that TAM also has efficacy on gastrointestinal neoplasms such as hepatocarcinoma and pancreatic carcinoma, and that the chemopreventive activities of TAM might be due to its abilities to inhibit cell growth and induce apoptosis. In the present study, we investigated the effects of tamoxifen on growth and apoptosis in the human bile duct carcinoma (BDC) cell line QBC939 using MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, classic DNA fragmentation agarose gel electrophoresis assay, PI single- and FITC/PI double-staining flow cytometry, and Western blotting. Our data revealed that TAM could significantly inhibit growth and induce apoptosis in QBC939 cells. Increased expression of p53 was observed in TAM-treated cells, indicating that p53 might play an important role in TAM-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of TAM on BDC.

Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

International Nuclear Information System (INIS)

Zhou, Wenchao; Bao, Shideng

2014-01-01

Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described

Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

Energy Technology Data Exchange (ETDEWEB)

Zhou, Wenchao; Bao, Shideng, E-mail: baos@ccf.org [Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States)

2014-03-26

Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described.

Reacción sistémica tras la ingesta de una oruga procesionaria del pino: ¿Manejo conservador?

OpenAIRE

Casado Verrier, Esther; Carro Rodríguez, Miguel A; Cancho, María de la Parte; Piñeiro Pérez, Roi

2016-01-01

La oruga procesionaria del pino, forma larvaria de la mariposa nocturna Thaumetopoea pityocampa, es una de las principales plagas forestales del sur de Europa. Con frecuencia, estas orugas producen reacciones locales en humanos debidas a los pelillos urticantes microscópicos que las recubren. La mayoría de los síntomas ocasionados son cutáneos, como urticaria aguda, y son mucho más infrecuentes las reacciones sistémicas. Se presenta un caso de reacción sistémica, con edema orofacial, babeo y ...

Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

International Nuclear Information System (INIS)

Veronesi, Andrea; Miolo, GianMaria; Magri, Maria D; Crivellari, Diana; Scalone, Simona; Bidoli, Ettore; Lombardi, Davide

2010-01-01

A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients. From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients. Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients. This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far

Comparison of tamsulosin plus serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia in Korean men: 1-year randomized open label study.

Science.gov (United States)

Ryu, Young Woo; Lim, Song Won; Kim, Jung Hoon; Ahn, Seung Hyun; Choi, Jae Duck

2015-01-01

In Korea, increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH. Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies. The present study was designed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH. One hundred forty men with symptomatic BPH (IPSS≥10) were recruited in our hospital for a 12-month, open-label, randomized trial. Patients were randomly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day (n=60) or tamsulosin 0.2 mg/day only (n=60). Prostate volume and PSA were measured at baseline and at end-point, whereas total IPSS, and its storage and voiding subscores, LUTS-related QoL, Qmax, and PVR were evaluated at baseline and later every 6 months. Total 103 patients were finally available: 50 in the TAM+SR group and 53 in the TAM group. At 12 months, total IPSS decreased by 5.8 with TAM+SR and 5.5 with TAM (p=0.693); the storage symptoms improved significantly more with TAM+SR (-1.7 vs. -0.8 with TAM, p=0.024). This benefit with regard to storage symptom in the TAM+SR group lasts at 12 months (-1.9 vs. -0.9, p=0.024). The changes of voiding subscore, LUTS-related QoL, Qmax, PVR, PSA, and prostate volume showed no significant differences between the TAM+SR and TAM groups. During the treatment period, 8 patients (16.9%) with TAM and 10 (20%) with TAM+SR had drug-related adverse reactions, which included ejaculatory disorders, postural hypotension, dizziness, headache, gastro-intestinal disorders, rhinitis, fatigue and asthenia. The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment. © 2015 S. Karger AG, Basel.

User Acceptance of the Intranet in Restaurant Franchise Systems: An Empirical Study

OpenAIRE

Park, Kunsoon

2006-01-01

This research study examined the acceptance of the intranet in restaurant franchise systems. The widely accepted Technology Acceptance Model (TAM) developed by Davis (1986, 1989) was the basis for this study. TAM is an excellent model to predict information technology (IT) usage and is based on the Theory of Reasoned Action (TRA). Therefore, TAM was adopted in this study of intranet acceptance. Furthermore, this study attempted to see if the earlier results of TAM are still valid. The origina...

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

DEFF Research Database (Denmark)

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S

2016-01-01

PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor......-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards......). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age...

Acceptance of Internet Banking Systems among Young Managers

International Nuclear Information System (INIS)

Ariff, Mohd Shoki Md; Yeow S M; Zakuan, Norhayati; Bahari, Ahamad Zaidi

2013-01-01

The aim of this paper is to determine acceptance of internet banking system among potential young users, specifically future young managers. The relationships and the effects of computer self-efficacy (CSE) and extended technology acceptance model (TAM) on the behavioural intention (BI) to use internet banking system were examined. Measurement of CSE, TAM and BI were adapted from previous studies. However construct for TAM has been extended by adding a new variable which is perceived credibility (PC). A survey through questionnaire was conducted to determine the acceptance level of CSE, TAM and BI. Data were obtained from 275 Technology Management students, who are pursuing their undergraduate studies in a Malaysia's public university. The confirmatory factor analysis performed has identified four variables as determinant factors of internet banking acceptance. The first variable is computer self-efficacy (CSE), and another three variables from TAM constructs which are perceived usefulness (PU), perceived ease of use (PE) and perceived credibility (PC). The finding of this study indicated that CSE has a positive effect on PU and PE of the Internet banking systems. Respondents' CSE was positively affecting their PC of the systems, indicating that the higher the ability of one in computer skills, the higher the security and privacy issues of PC will be concerned. The multiple regression analysis indicated that only two construct of TAM; PU and PC were significantly associated with BI. It was found that the future managers' CSE indirectly affects their BI to use the internet banking systems through PU and PC of TAM. TAM was found to have direct effects on respondents' BI to use the systems. Both CSE and the PU and PC of TAM were good predictors in understanding individual responses to information technology. The role of PE of the original TAM to predict the attitude of users towards the use of information technology systems was surprisingly insignificant.

Tumor-associated macrophages: Oblivious confederates in invasive mammary carcinoma

Directory of Open Access Journals (Sweden)

Imtiaz Ahmed

2017-01-01

Full Text Available Background: The infiltrating margins of carcinomas are associated with presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Amongst the inflammatory cells, Tumor Associated Macrophages (TAMs play a key role in the tumorigenesis. This study elucidates the density of TAMs in invasive mammary carcinomas and attempts to establish aa association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Materials and Methods: 90 diagnosed archival cases of invasive mammary carcinomas at a tertiary care centre were included. Density of TAMs was assessed by using CD68 which is a pan-macrophage marker by immunohistochemistry on the archival tissue blocks. The density TAMs (CD68 positive cells was dichotomised into high (>50 CD68 positive cells/ HPF and low (<5050 CD68 positive cells/ HPF and compared with the above mentioned pathological variables using appropriate statistical tests. Results: The density of TAMs was significantly higher around the infiltrating edge of the carcinoma in comparison to the adjoining normal terminal duct lobular units. The density of TAMs was more in the infiltrating edge of the tumor than within the tumor nodule/nests. A higher TAM density showed a significant association in tumors having large tumor size, higher histological grade, nodal metastasis, absence of ER and PR expression and Her2Neu overexpression (p value <0.05. Conclusion: TAMs play an important role in tumor progression in invasive mammary carcinomas. This is as a result of the multiple roles enacted by TAMs in the various stages of tumor development starting from tumor growth, invasion, angiogenesis and metastases. Targeted therapy against TAMs has great potential in the being important components of future treatment strategies against breast carcinomas.

Acceptance of Internet Banking Systems among Young Managers

Science.gov (United States)

Ariff, Mohd Shoki Md; M, Yeow S.; Zakuan, Norhayati; Zaidi Bahari, Ahamad

2013-06-01

The aim of this paper is to determine acceptance of internet banking system among potential young users, specifically future young managers. The relationships and the effects of computer self-efficacy (CSE) and extended technology acceptance model (TAM) on the behavioural intention (BI) to use internet banking system were examined. Measurement of CSE, TAM and BI were adapted from previous studies. However construct for TAM has been extended by adding a new variable which is perceived credibility (PC). A survey through questionnaire was conducted to determine the acceptance level of CSE, TAM and BI. Data were obtained from 275 Technology Management students, who are pursuing their undergraduate studies in a Malaysia's public university. The confirmatory factor analysis performed has identified four variables as determinant factors of internet banking acceptance. The first variable is computer self-efficacy (CSE), and another three variables from TAM constructs which are perceived usefulness (PU), perceived ease of use (PE) and perceived credibility (PC). The finding of this study indicated that CSE has a positive effect on PU and PE of the Internet banking systems. Respondents' CSE was positively affecting their PC of the systems, indicating that the higher the ability of one in computer skills, the higher the security and privacy issues of PC will be concerned. The multiple regression analysis indicated that only two construct of TAM; PU and PC were significantly associated with BI. It was found that the future managers' CSE indirectly affects their BI to use the internet banking systems through PU and PC of TAM. TAM was found to have direct effects on respondents' BI to use the systems. Both CSE and the PU and PC of TAM were good predictors in understanding individual responses to information technology. The role of PE of the original TAM to predict the attitude of users towards the use of information technology systems was surprisingly insignificant.

Liposomal formulation of α-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

International Nuclear Information System (INIS)

Turanek, Jaroslav; Wang Xiufang; Knoetigova, Pavlina; Koudelka, Stepan; Dong Lanfeng; Vrublova, Eva; Mahdavian, Elahe; Prochazka, Lubomir; Sangsura, Smink; Vacek, Antonin; Salvatore, Brian A.; Neuzil, Jiri

2009-01-01

The vitamin E analogue α-tocopheryl succinate (α-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of α-tocopheryl maleamide (α-TAM), an esterase-resistant analogue of α-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of α-TAM towards cancer cells (MCF-7, B16F10) compared to α-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that α-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both α-TOS and α-TAM to solve the problem with cytotoxicity of free α-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal α-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of α-TAM and α-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of α-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of α-TOS. Thus, the liposomal formulation of α-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial.

Science.gov (United States)

Yang, H; Zong, X; Yu, Y; Shao, G; Zhang, L; Qian, C; Bian, Y; Xu, X; Sun, W; Meng, X; Ding, X; Chen, D; Zou, D; Xie, S; Zheng, Y; Zhang, J; He, X; Sun, C; Yu, X; Ni, J

2013-08-06

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer. This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months. Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (Pwomen in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups. The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.

Integrating truck arrival management into tactical operation planning at container terminals

DEFF Research Database (Denmark)

Yang, Zhong-Zhen; Chen, Gang; Song, Dong-Ping

2013-01-01

Truck arrival management (TAM) has been recognized as an effective solution to alleviate the gate congestion at container terminals. To further utilize TAM in improving the overall terminal performance, this study integrates TAM with the other terminal operations at a tactical level. An integrated...

Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes

NARCIS (Netherlands)

Movahedi, Kiavash; Laoui, Damya; Gysemans, Conny; Baeten, Martijn; Stangé, Geert; van den Bossche, Jan; Mack, Matthias; Pipeleers, Daniel; In't Veld, Peter; de Baetselier, Patrick; van Ginderachter, Jo A.

2010-01-01

Tumor-associated macrophages (TAM) form a major component of the tumor stroma. However, important concepts such as TAM heterogeneity and the nature of the monocytic TAM precursors remain speculative. Here, we show for the first time that mouse mammary tumors contained functionally distinct subsets

Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake

DEFF Research Database (Denmark)

Madsen, Daniel Hargbøl; Jürgensen, Henrik Jessen; Siersbæk, Majken Storm

2017-01-01

-associated macrophage (TAM)-like cells that degrade collagen in a mannose receptor-dependent manner. Accordingly, mannose-receptor-deficient mice display increased intratumoral collagen. Whole-transcriptome profiling uncovers a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage......-ablation studies reveal that collagen-degrading TAMs originate from circulating CCR2+ monocytes. This study identifies a function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation. Madsen et...

Treatment Options for Childhood Acute Myeloid Leukemia, Childhood Chronic Myelogenous Leukemia, Juvenile Myelomonocytic ...

Science.gov (United States)

... can affect the blood and bone marrow. Transient abnormal myelopoiesis (TAM) TAM is a disorder of the bone marrow that can develop in ... is sometimes used to treat MDS or transient abnormal myelopoiesis (TAM). ... caused by the disease or its treatment. All patients with leukemia receive ...

Stages of Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Science.gov (United States)

... can affect the blood and bone marrow. Transient abnormal myelopoiesis (TAM) TAM is a disorder of the bone marrow that can develop in ... is sometimes used to treat MDS or transient abnormal myelopoiesis (TAM). ... caused by the disease or its treatment. All patients with leukemia receive ...

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.

Science.gov (United States)

Pu, Wei-Ling; Sun, Li-Kang; Gao, Xiu-Mei; Rüegg, Curzio; Cuendet, Muriel; Hottiger, Micheal O; Zhou, Kun; Miao, Lin; Zhang, Yun-Sha; Gebauer, Margaret

2017-10-01

Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

DEFF Research Database (Denmark)

Sørensen, M D; Dahlrot, R H; Boldt, H B

2018-01-01

AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...... automated quantitative double immunofluorescence. METHODS: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified...... by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno- and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery...

Dialectic Antidotes to Critics of the Technology Acceptance Model: Conceptual, Methodological, and Replication Treatments for Behavioural Modelling in Technology-Mediated Environments

Directory of Open Access Journals (Sweden)

Weng Marc Lim

2018-01-01

Full Text Available The technology acceptance model (TAM is a prominent and parsimonious conceptual lens that is often applied for behavioural modelling in technology-mediated environments. However, TAM has received a great deal of criticism in recent years. This article aims to address some of the most pertinent issues confronting TAM through a rejoinder that offers dialectic antidotes—in the form of conceptual, methodological, and replication treatments—to support the continued use of TAM to understand the peculiarities of user interactions with technology in technology-mediated environments. In doing so, this article offers a useful response to a common but often inadequately answered question about how TAM can continue to be relevant for behavioural modelling in contemporary technology-mediated environments.

Cancer-promoting tumor-associated macrophages: new vistas and open questions.

Science.gov (United States)

Mantovani, Alberto; Germano, Giovanni; Marchesi, Federica; Locatelli, Marco; Biswas, Subhra K

2011-09-01

Tumor-associated macrophages (TAMs) are key components of the tumor macroenvironment. Cancer- and host cell-derived signals generally drive the functions of TAMs towards an M2-like polarized, tumor-propelling mode; however, when appropriately re-educated. TAMs also have the potential to elicit tumor destructive reactions. Here, we discuss recent advances regarding the immunobiology of TAMs and highlight open questions including the mechanisms of their accumulation (recruitment versus proliferation), their diversity and how to best therapeutically target these cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iodine-125-labelled tamoxifen is differentially cytoxic to cells containing oestrogen receptors

International Nuclear Information System (INIS)

Bloomer, W.D.; McLaughlin, W.H.; Weichselbaum, R.R.

1980-01-01

Tamoxifen, a non-steroidal anti-oestrogen competes with 17 - oestradiol for oestrogen receptor protein and is translocated to the nucleus. Carrier-free 125 I-TAM was tested for cytotoxicity in oestrogen receptor rich (human breast cancer MCF-7) and poor (V-79 Chinese hamster) cells. 125 I-TAM was differentially cytotoxic to MCF-7 cells. The D 37 values for MCF-7 and V-79 cells were 0.5 and 1.5 pCi/cell respectively. No radiotoxicity was observed with Na 125 I at doses equal to 125 I-TAM; iodide was effectively excluded from both cell lines and remained in the extracellular space. Also, nonradioactive 127 I-TAM and TAM were both non-toxic when tested at levels comparable to 125 I-TAM. It is suggested that the marked cytotoxicity in MCF-7 cells results from close approximation of 125 I with the genetic apparatus as a result of direct charging of specific nuclear receptors and/or translocation of 125 I-TAM receptor complexes from the cytoplasm to the nucleus, and that the minimal toxicity in V-79 cells reflects transmitted cytoplasmic radiation effects, limited direct nuclear charging and/or limited nuclear translocation resulting from the relative paucity of oestrogen in the cells. (U.K.)

77 FR 10775 - United States v. SG Interests I LTD., et al.; Proposed Final Judgment and Competitive Impact...

Science.gov (United States)

2012-02-23

... a related qui tam case also filed in United States District Court for the District of Colorado... PROPOSED FINAL JUDGMENT The proposed Final Judgment relates to a qui tam action captioned United States ex... this action and the qui tam action arise from common facts related to BLM auctions in February 2005 and...

Validating the Technology Acceptance Model in the Context of the Laboratory Information System-Electronic Health Record Interface System

Science.gov (United States)

Aquino, Cesar A.

2014-01-01

This study represents a research validating the efficacy of Davis' Technology Acceptance Model (TAM) by pairing it with the Organizational Change Readiness Theory (OCRT) to develop another extension to the TAM, using the medical Laboratory Information Systems (LIS)--Electronic Health Records (EHR) interface as the medium. The TAM posits that it is…

Cell death induced by tamoxifen in human blood lymphocytes cultivated in vitro = Morte celular induzida pelo tamoxifeno em linfócitos humanos cultivados in vitro

Directory of Open Access Journals (Sweden)

Selma Candelária Genari

2010-10-01

Full Text Available Many chemotherapeutic agents with a potential against solid tumors or leukemia can cause lymphopenia. Tamoxifen (TAM is a synthetic non-steroidal anti-estrogen drug employed in female breast cancer treatment. The present study investigated the capacity of TAM to induce cell death in human lymphocytes cultivated in vitro. Lymphocytes were obtained from young (25-30 years; n = 3 and elderly women (58-77 years; n = 3 and cultivated for 24 or 48h, with or without TAM (20 ƒÊM. After the culture, cell viability, immunocytochemical response and ultrastructure were evaluated. TAM affected lymphocytes in a time- dependent manner, and cells obtained from elderly women were the most sensitive to TAM. Immunocytochemicalanalysis evidenced higher frequency of apoptosis in treated cells, and the ultrastructural study revealed autophagic vacuoles, differing from the controls. In summary, the treated lymphocytes were affected by TAM, leading to cell death by apoptosis and autophagy.Muitos agentes quimioterapicos com potencial contra tumores solidos ou leucemias podem causar linfopenia. O Tamoxifeno (TAM e um agente antiestrogeno nao-esteroidal empregado no tratamento de cancer de mama feminino. O presente trabalho investigou a capacidade do TAM em induzir morte celular em linfocitos humanos cultivados in vitro. Oslinfocitos foram obtidos de mulheres jovens (25-30 anos; n = 3 e idosas (58-77 anos; n = 3 e cultivados por 24 ou 48h, com ou sem TAM (20 ƒÊM. Apos a cultura, foram analisadas a viabilidade celular, a resposta imunocitoquimica e a ultraestrutura. Os resultados indicam que o Tamoxifeno induziu morte celular em linfocitos de ambos os grupos, entretanto, as celulas das mulheres idosas apresentaram-se mais sensiveis ao tratamento. A analise imunocitoquimica mostrou maior frequencia de apoptose nas celulas tratadas e o estudo ultraestrutural revelou vacuolos autofagicos nos linfocitos expostos ao Tamoxifeno. Em conclusao, nosso estudo revelou que o TAM

Characterization of dynamics in complex lyophilized formulations: I. Comparison of relaxation times measured by isothermal calorimetry with data estimated from the width of the glass transition temperature region.

Science.gov (United States)

Chieng, Norman; Mizuno, Masayasu; Pikal, Michael

2013-10-01

The purposes of this study are to characterize the relaxation dynamics in complex freeze dried formulations and to investigate the quantitative relationship between the structural relaxation time as measured by thermal activity monitor (TAM) and that estimated from the width of the glass transition temperature (ΔT(g)). The latter method has advantages over TAM because it is simple and quick. As part of this objective, we evaluate the accuracy in estimating relaxation time data at higher temperatures (50 °C and 60 °C) from TAM data at lower temperature (40 °C) and glass transition region width (ΔT(g)) data obtained by differential scanning calorimetry. Formulations studied here were hydroxyethyl starch (HES)-disaccharide, HES-polyol, and HES-disaccharide-polyol at various ratios. We also re-examine, using TAM derived relaxation times, the correlation between protein stability (human growth hormone, hGH) and relaxation times explored in a previous report, which employed relaxation time data obtained from ΔT(g). Results show that most of the freeze dried formulations exist in single amorphous phase, and structural relaxation times were successfully measured for these systems. We find a reasonably good correlation between TAM measured relaxation times and corresponding data obtained from estimates based on ΔT(g), but the agreement is only qualitative. The comparison plot showed that TAM data are directly proportional to the 1/3 power of ΔT(g) data, after correcting for an offset. Nevertheless, the correlation between hGH stability and relaxation time remained qualitatively the same as found with using ΔT(g) derived relaxation data, and it was found that the modest extrapolation of TAM data to higher temperatures using ΔT(g) method and TAM data at 40 °C resulted in quantitative agreement with TAM measurements made at 50 °C and 60 °C, provided the TAM experiment temperature, is well below the Tg of the sample. Copyright © 2013 Elsevier B.V. All rights

A randomized trial of tamoxifen with or without breast radiation in women over 50 years of age with T1/2 N0 disease

International Nuclear Information System (INIS)

Fyles, A.; Manchul, L.; McCready, D.; Merante, P.; Pintilie, M.; Trudeuau, M.; Olivotto, I.; Weir, L.

2003-01-01

To determine the effect of breast radiation (RT) on disease-free survival (DFS) and ipsilateral breast relapse (IBR) in women over 50 with T1 and T2 node negative breast cancer. Between December 1992 and June 2000, 769 women were randomized to RT and Tamoxifen (Tam) 20 mg daily for 5 years or Tam alone. Median age was 68 years, 639 patients had pT1 lesions and ER/PR were positive in 700 patients. Six hundred and thirty-four patients had pathologically negative nodes and 135 over age 65 were clinically node negative. Median follow-up was 5.6 years and patient and tumour characteristics were well balanced between the two arms. Overall, there were 54 relapses from breast cancer in the Tam arm and 27 in the Tam + RT arm. IBR at 5 years was 7.7% in the Tam arm compared to 0.6% in the Tam + RT group (p<0.0001). Significant factors for breast relapse and DFS at 5 years included tumour size (p=0.02 and 0.0001 respectively), hormone-receptor status (p=0.0008 and 0.0001), grade (p=0.001 and 0.003) and treatment arm (p=0.0001 and 0.004). Four-hundred and nineteen patients with low-risk features (T1, receptor-positive and grade 1/2) treated with Tam alone had a 5% risk of IBR at 5 years, increasing to 10% at 8 years. There was no difference in relapse at regional or distant sites, or in the contralateral breast. No difference was seen in the number of deaths due to breast cancer (13 and 11 for Tam + RT and Tam, respectively), nor in OS (93% at 5 years in both arms). Tamoxifen and breast RT results in a significantly lower rate of breast relapse than Tam alone in women over 50 with node-negative breast cancer. There does not appear to be a low-risk group who can be treated with Tamoxifen without breast radiation

Tamoxifen induces the expression of maspin through estrogen receptor-alpha.

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Liu, Zesheng; Shi, Heidi Y; Nawaz, Zafar; Zhang, Ming

2004-06-08

Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERalpha but not estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between -90and+87 bp but not the HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound ERalpha may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERalpha mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE-luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha to the maspin promoter region. This finding indicates that one of the pathways for cancer

Tamoxifen attenuates development of lithium-induced nephrogenic diabetes insipidus in rats

DEFF Research Database (Denmark)

Tingskov, Stine Julie; Hu, Shan; Frøkiær, Jorgen

2018-01-01

of aquaporin-2 (AQP2), which are essential for water reabsorption of tubular fluid in the collecting duct. Sex hormones have previously been shown to affect the regulation of AQP2, so we tested whether tamoxifen (TAM), a selective estrogen receptor modulator, would attenuate lithium-induced alterations...... on renal water homeostasis. Rats were treated for 14 days with lithium and TAM treatment was initiated one week after onset of lithium administration. Lithium treatment resulted in severe polyuria and reduced AQP2 expression, which was ameliorated by TAM. Consistent with this, TAM attenuated downregulation...... of AQP2 and increased phosphorylation of the cAMP responsive element binding protein (CREB), which induced AQP2 expression, in freshly isolated inner medullary collecting duct suspension prepared from lithium-treated rats. In conclusion, TAM attenuated dose-dependently polyuria, impaired urine...

Effect of tamoxifen, methoxyprogesterone acetate and combined treatment on cellular proliferation and apoptosis in SKOV3/DDP cells via the regulation of vascular endothelial growth factor.

Science.gov (United States)

Wen, Lv; Hong, Ding; Yanyin, Wu; Mingyue, Zhang; Baohua, Li

2013-05-01

The aim of this study was to investigate the effect of tamoxifen (TAM), methoxyprogesterone acetate (MPA) and their combined treatment on cisplatin-resistant ovarian cancer SKOV3/DDP cells, as well as the potential mechanisms. MTT assay was used to investigate the effect of different concentrations (0.01, 0.1, 1, 10 and 100 μM) of TAM, MPA and their combined treatment on the proliferation of cisplatin-resistant ovarian cancer SKOV3/DDP cells. Flow cytometry was employed to analyze the cell cycle and apoptosis rate of SKOV3/DDP cells treated with medium concentration (10 μM) of TAM, MPA and their combined treatment. Change in the protein level of vascular endothelial growth factor (VEGF) in response to drug treatments was measured using Western-blot. The proliferation of SKOV3/DDP cells was inhibited by 1, 10 and 100 μM of TAM or MPA in a dose-dependent manner. Compared to the control group, 10 μM TAM could significantly arrest SKOV3/DDP cells in the G0/G1 stage and induce apoptosis (p < 0.01). However, 10 μM MPA only promoted cell apoptosis, while exhibited little effect on the cell cycle. We further found that 10 μM TAM could remarkably reduce the protein expression of VEGF, while 10 μM MPA only induce a slight reduction. Strikingly, the combined treatment of TAM and MPA exhibited additive effect on the proliferation, cell cycle, apoptosis rate and VEGF expression of SKOV3/DDP cells. We found that TAM, MPA and their combined treatment exhibited significant inhibitory effect on the cisplatin-resistant ovarian cancer SKOV3/DDP cells. Hence, TAM and MPA could be potential cytotoxic drugs to treat cisplatin-resistant patients with advanced ovarian cancer.

Examining the Moderating Effect of Individual-Level Cultural Values on Users' Acceptance of E-Learning in Developing Countries: A Structural Equation Modeling of an Extended Technology Acceptance Model

Science.gov (United States)

Tarhini, Ali; Hone, Kate; Liu, Xiaohui; Tarhini, Takwa

2017-01-01

In this study, we examine the effects of individual-level culture on the adoption and acceptance of e-learning tools by students in Lebanon using a theoretical framework based on the Technology Acceptance Model (TAM). To overcome possible limitations of using TAM in developing countries, we extend TAM to include "subjective norms" (SN)…

Experiment list: SRX1056357 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available || cell type=ES cells || treated with=2.5 µM tamoxifen (Tam) || chip antibody=none http://dbarchive.bioscien...tiate into specialized cells. 35337197,98.9,19.2,224 GSM1708671: input DNA +Tam R...2; Mus musculus; ChIP-Seq source_name=input DNA_+Tam || strain=J1 || genotype/variation=inducible SetDB1 KO

Secondary Instabilities and Spatiotemporal Chaos in Parametric Surface Waves

International Nuclear Information System (INIS)

Zhang, W.; Vinals, J.

1995-01-01

A 2D model is introduced to study the onset of parametric surface waves, their secondary instabilities, and the transition to spatiotemporal chaos. We obtain the stability boundary of a periodic standing wave above onset against Eckhaus, zigzag, and transverse amplitude modulations (TAM), as a function of the control parameter var-epsilon and the wavelength of the pattern. The Eckhaus and TAM boundaries cross at a finite value of var-epsilon, thus explaining the finite threshold for the TAM observed experimentally. At larger values of var-epsilon, a numerical solution reveals a transition to spatiotemporal chaotic states mediated by the TAM instability

Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2

DEFF Research Database (Denmark)

Hubackova, Sona; Davidova, Eliska; Rohlenova, Katerina

2018-01-01

and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent...... cells. In naturally aged mice treated with MitoTam for 4 weeks, we observed a significant decrease of senescence markers in all tested organs compared to non-treated animals. Mechanistically, we found that the susceptibility of senescent cells to MitoTam is linked to a very low expression level...... of adenine nucleotide translocase-2 (ANT2), inherent to the senescent phenotype. Restoration of ANT2 in senescent cells resulted in resistance to MitoTam, while its downregulation in non-senescent cells promoted their MitoTam-triggered elimination. Our study documents a novel, translationally intriguing role...

Global characterization of signalling networks associated with tamoxifen resistance in breast cancer

DEFF Research Database (Denmark)

Browne, Brigid C.; Hochgräfe, Falko; Wu, Jianmin

2013-01-01

R cells. Phosphorylation of the tyrosine kinase Yes and expression of the actin‐binding protein myristoylated alanine‐rich C‐kinase substrate (MARCKS) were increased two‐ and eightfold in TamR cells respectively, and these proteins were selected for further analysis. Knockdown of either protein in Tam......Acquired resistance to the anti‐estrogen tamoxifen remains a significant challenge in breast cancer management. In this study, we used an integrative approach to characterize global protein expression and tyrosine phosphorylation events in tamoxifen‐resistant MCF7 breast cancer cells (Tam...... was perturbed in TamR cells, together with pathways enriched for proteins associated with growth factor, cell–cell and cell matrix‐initiated signalling. Consistent with known roles for Ras/MAPK and PI3‐kinase signalling in tamoxifen resistance, tyrosine‐phosphorylated MAPK1, SHC1 and PIK3R2 were elevated in Tam...

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

International Nuclear Information System (INIS)

Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

2014-01-01

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

Energy Technology Data Exchange (ETDEWEB)

Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

2014-08-13

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

International Nuclear Information System (INIS)

Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang

2013-01-01

Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80 + macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206 + TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer

The novel biomarker of alternative macrophage activation, soluble mannose receptor (sMR/sCD206): Implications in multiple myeloma

DEFF Research Database (Denmark)

Andersen, Morten N; Andersen, Niels F; Rødgaard-Hansen, Sidsel

2015-01-01

Tumor-associated macrophages (TAMs) play an important role in the pathophysiology of human malignancies. They support growth of cancer cells by promoting angiogenesis, and by inhibiting tumour cell apoptosis and anti-tumor immune reactions. Several membrane proteins are well-described markers...... of human TAMs, including the haemoglobin scavenger receptor CD163 and the macrophage mannose receptor (MR/CD206). Interestingly, both CD163 and MR exist as soluble serum proteins (sCD163 and sMR) that may reflect the activation state of tissue macrophages, including TAMs. Here, we report the first data...... showed significant association with sCD163, which may indicate common origin from CD163+MR+TAMs....

Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

International Nuclear Information System (INIS)

Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

2011-01-01

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163 + cells were significantly increased based on the pathological grade. CD163 + cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163 + cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4 + and CD8 + T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163 + TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC

Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

Energy Technology Data Exchange (ETDEWEB)

Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

2011-09-28

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

Compound list: tamoxifen [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available tamoxifen TMX 00054 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/tam...oxifen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/tam...oxifen.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/tam...open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/tamoxifen.Rat.in_vivo.Liver.Repeat.zip ...

Whirling disease among snake river cutthroat trout in two spring streams in Wyoming

Science.gov (United States)

Hubert, W.A.; Joyce, M.P.; Gipson, R.; Zafft, D.; Money, D.; Hawk, D.; Taro, B.

2002-01-01

We assessed endemic age-0 cutthroat trout Oncorhynchus clarki for evidence of pathology associated with Myxobolus cerebralis in two streams formed by springs in western Wyoming. We hypothesized that the location of spawning sites in spring streams would affect the extent of exposure of cutthroat trout fry to M. cerebralis triactinomyxons (tams), occurrence of the parasite in their bodies, and clinical signs of whirling disease. The spring streams were warm relative to nearby streams flowing from the mountains or spawning and emergence of fry was early compared with fish in mountain streams. Tams were abundant early in the summer and clinical signs of whirling disease among age-0 fish were seen as early as mid-June in one stream. There were high densities of tams in one stream, and densities declined with upstream progression from May through July, whereas in the other stream, low densities of tams were observed in the downstream portion early in the summer, and they were not detected in July and August. Age-0 cutthroat trout were abundant; clinical signs of whirling disease were evident, and histological evidence of whirling disease was common in the stream where tams were abundant. Low densities of age-0 cutthroat trout and no clinical signs of whirling disease were observed in the stream where tams were not abundant. Among sentinel fish in the stream with abundant tams, we found extensive occurrence of M. cerebralis, with many fish showing clinical signs and histological evidence of pathology associated with M. cerebralis. The proportion of sentinel fish with clinical and histological signs of whirling disease decreased with upstream progression. In the stream with low tam, densities sentinel fish became infected with M. cerebralis, but there were essentially no clinical signs or histological indications of whirling disease. ?? 2002 by the American Fisheries Society.

Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells.

Science.gov (United States)

Mao, Zonglei; Zhou, Jin; Luan, Junwei; Sheng, Weihua; Shen, Xiaochun; Dong, Xiaoqiang

2014-03-01

Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity

Science.gov (United States)

Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N.; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S.

2012-01-01

Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15–transduced NKT cells. PMID:22565311

IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity.

Science.gov (United States)

Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S

2012-06-01

Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15-transduced NKT cells.

Design of a Tritium-in-air-monitor using field programmable gate arrays

International Nuclear Information System (INIS)

McNelles, Phillip; Lu, Lixuan

2015-01-01

Field Programmable Gate Arrays (FPGAs) have recently garnered significant interest for certain applications within the nuclear field. Some applications of these devices include Instrumentation and Control (I and C) systems, pulse measurement systems, particle detectors and health physics purposes. In CANada Deuterium Uranium (CANDU) nuclear power plants, the use of heavy water (D2O) as the moderator leads to the increased production of Tritium, which poses a health risk and must be monitored by Tritium-In-Air Monitors (TAMs). Traditional TAMs are mostly designed using microprocessors. More recent studies show that FPGAs could be a potential alternative to implement the electronic logic used in radiation detectors, such as the TAM, more effectively. In this paper, an FPGA-based TAM is designed and constructed in a laboratory setting using an FPGA-based cRIO system. New functionalities, such as the detection of Carbon-14 and the addition of noble gas compensation are incorporated into a new FPGA-based TAM. Additionally, all of the standard functions included in the original microprocessor-based TAM, such as tritium detection, gamma compensation, pump and air flow control, and background and thermal drift corrections were also implemented. The effectiveness of the new design is demonstrated through simulations as well as laboratory testing on the prototype system. (author)

Reactivity Control of Rhodium Cluster Ions by Alloying with Tantalum Atoms.

Science.gov (United States)

Mafuné, Fumitaka; Tawaraya, Yuki; Kudoh, Satoshi

2016-02-18

Gas phase, bielement rhodium and tantalum clusters, RhnTam(+) (n + m = 6), were prepared by the double laser ablation of Rh and Ta rods in He carrier gas. The clusters were introduced into a reaction gas cell filled with nitric oxide (NO) diluted with He and were subjected to collisions with NO and He at room temperature. The product species were observed by mass spectrometry, demonstrating that the NO molecules were sequentially adsorbed on the RhnTam(+) clusters to form RhnTam(+)NxOx (x = 1, 2, 3, ...) species. In addition, oxide clusters, RhnTam(+)O2, were also observed, suggesting that the NO molecules were dissociatively adsorbed on the cluster, the N atoms migrated on the surface to form N2, and the N2 molecules were released from RhnTam(+)N2O2. The reactivity, leading to oxide formation, was composition dependent: oxide clusters were dominantly formed for the bielement clusters containing both Rh and Ta atoms, whereas such clusters were hardly formed for the single-element Rhn(+) and Tam(+) clusters. DFT calculations indicated that the Ta atoms induce dissociation of NO on the clusters by lowering the dissociation energy, whereas the Rh atoms enable release of N2 by lowering the binding energy of the N atoms on the clusters.

Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

International Nuclear Information System (INIS)

Jang, Ji-Young; Lee, Jong-Kuen; Jeon, Yoon-Kyung; Kim, Chul-Woo

2013-01-01

Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

Experiment list: SRX1056356 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available O || cell type=ES cells || treated with=2.5 µM tamoxifen (Tam) || chip antibody=H3K27me3 (Millipore: 07-449)...specialized cells. 43433717,97.9,45.2,1333 GSM1708670: H3K27me3 ChIPSeq+Tam R2; M...us musculus; ChIP-Seq source_name=H3K27me3_ChIPSeq+Tam || strain=J1 || genotype/variation=inducible SetDB1 K

Inhibition of the MAPK pathway alone is insufficient to account for all of the cytotoxic effects of naringenin in MCF-7 breast cancer cells

Directory of Open Access Journals (Sweden)

Lauren Eanes

2016-12-01

Full Text Available Estrogen receptor (ER antagonists such as tamoxifen (Tam have been used successfully to treat ER+ breast cancers for more than 30 years. Unfortunately, long term use of Tam can result in resistance. Tam resistance is associated with the activation of growth factor signaling pathways that promote cell proliferation and survival. The mitogen-activated protein kinase (MAPK, is up-regulated in Tam resistant (Tam-R cells. Previous studies have reported that the flavanone, naringenin (Nar can inhibit cell proliferation and induce apoptosis in ER+ breast cancer cells. Furthermore, Nar has been shown to inhibit the MAPK signaling pathways in MCF-7 cells. In this report we investigated whether inhibition of MAPK alone is mediating the effects of Nar on cell proliferation and viability. These studies will determine the mechanism of action of Nar. Tam-R MCF-7 breast cancer cells were treated with Nar or U0126, a MAPK kinase inhibitor. Our studies show that while both U0126 and Nar impaired cell proliferation and viability the combination of U0126 and Nar resulted in greater inhibition of cell viability than either compound alone. It has been previously reported that Nar can bind the ER. Our lab has also shown that Nar localizes ERα to a peri-nuclear region of the cell. Confocal microscopy revealed that in U0126 treated cells ERα displayed an even distribution across the cytoplasm as seen in untreated Tam-R cells. These studies suggest that MAPK is not the only target of Nar.

Tamoxifen and ICI 182,780 activate hypothalamic G protein-coupled estrogen receptor 1 to rapidly facilitate lordosis in female rats.

Science.gov (United States)

Long, Nathan; Long, Bertha; Mana, Asma; Le, Dream; Nguyen, Lam; Chokr, Sima; Sinchak, Kevin

2017-03-01

In the female rat, sexual receptivity (lordosis) can be facilitated by sequential activation of estrogen receptor (ER) α and G protein-coupled estrogen receptor 1 (GPER) by estradiol. In the estradiol benzoate (EB) primed ovariectomized (OVX) rat, EB initially binds to ERα in the plasma membrane that complexes with and transactivates metabotropic glutamate receptor 1a to activate β-endorphin neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). This activates MPN μ-opioid receptors (MOP), inhibiting lordosis. Infusion of non-esterified 17β-estradiol into the ARH rapidly reduces MPN MOP activation and facilitates lordosis via GPER. Tamoxifen (TAM) and ICI 182,780 (ICI) are selective estrogen receptor modulators that activate GPER. Therefore, we tested the hypothesis that TAM and ICI rapidly facilitate lordosis via activation of GPER in the ARH. Our first experiment demonstrated that injection of TAM intraperitoneal, or ICI into the lateral ventricle, deactivated MPN MOP and facilitated lordosis in EB-primed rats. We then tested whether TAM and ICI were acting rapidly through a GPER dependent pathway in the ARH. In EB-primed rats, ARH infusion of either TAM or ICI facilitated lordosis and reduced MPN MOP activation within 30min compared to controls. These effects were blocked by pretreatment with the GPER antagonist, G15. Our findings demonstrate that TAM and ICI deactivate MPN MOP and facilitate lordosis in a GPER dependent manner. Thus, TAM and ICI may activate GPER in the CNS to produce estrogenic actions in neural circuits that modulate physiology and behavior. Published by Elsevier Inc.

Improving the efficacy of hormone therapy in breast cancer: The role of cholesterol metabolism in SERM-mediated autophagy, cell differentiation and death.

Science.gov (United States)

Leignadier, Julie; Dalenc, Florence; Poirot, Marc; Silvente-Poirot, Sandrine

2017-11-15

Breast cancer (BC) is one of the most common female cancers in the world, with estrogen receptor (ER)-positive BC the most frequent subtype. Tamoxifen (Tam) is an effective drug that competitively binds to the ER and is routinely used for the treatment of ER-positive BC. However, a number of ER-positive BC do not respond to Tam treatment and acquired resistance is often observed, constituting a major challenge for extending patient life expectancy. The mechanisms responsible for these treatment failures remain unclear, indicating the requirement for other targets and better predictors for patient response to Tam. One of Tam's off-targets of interest is the microsomal antiestrogen binding site (AEBS), a multiproteic complex made up of the cholesterol-5,6-epoxide hydrolase (ChEH) enzymes that are involved in the late stages of cholesterol biosynthesis. Tam and other selective ER modulators stimulate oxidative stress and inhibit the ChEH subunits at pharmacological doses, triggering the production and accumulation of cholesterol-5,6-epoxide metabolites responsible for BC cell differentiation and death. However, inhibition of the cholesterogenic activity of the AEBS subunits also induces the accumulation of sterol precursors, which triggers a survival autophagy to impair Tam's efficacy. Altogether, these studies have highlighted the involvement of cholesterol metabolism in the pharmacology of Tam that has provided new clues on how to improve its therapeutic efficacy in both BC and other cancers as well as offering a new rationale for developing more efficient drugs for BC treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of tamoxifen on neuronal morphology, connectivity and biochemistry of hypothalamic ventromedial neurons: Impact on the modulators of sexual behavior.

Science.gov (United States)

Sá, Susana I; Teixeira, Natércia; Fonseca, Bruno M

2018-01-01

Tamoxifen (TAM) is a selective estrogen receptor modulator, widely used in the treatment and prevention of estrogen-dependent breast cancer. Although with great clinical results, women on TAM therapy still report several side effects, such as sexual dysfunction, which impairs quality of life. The anatomo-functional substrates of the human sexual behavior are still unknown; however, these same substrates are very well characterized in the rodent female sexual behavior, which has advantage of being a very simple reflexive response, dependent on the activation of estrogen receptors (ERs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl). In fact, in the female rodent, the sexual behavior is triggered by increasing circulation levels of estradiol that changes the nucleus neurochemistry and modulates its intricate neuronal network. Therefore, we considered of notice the examination of the possible neurochemical alterations and the synaptic plasticity impairment in VMNvl neurons of estradiol-primed female rats treated with TAM that may be in the basis of this neurological disorder. Accordingly, we used stereological and biochemical methods to study the action of TAM in axospinous and axodendritic synaptic plasticity and on ER expression. The administration of TAM changed the VMNvl neurochemistry by reducing ERα mRNA and increasing ERβ mRNA expression. Furthermore, present results show that TAM induced neuronal atrophy and reduced synaptic connectivity, favoring electrical inactivity. These data suggest that these cellular and molecular changes may be a possible neuronal mechanism of TAM action in the disruption of the VMNvl network, leading to the development of behavioral disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

Directory of Open Access Journals (Sweden)

Kim Wun-Jae

2011-04-01

Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

The Comparison of Thyroarytenoid Muscle Myectomy and Type II Thyroplasty for Spasmodic Dysphonia.

Science.gov (United States)

Nomoto, Masaki; Tokashiki, Ryoji; Hiramatsu, Hiroyuki; Konomi, Ujimoto; Motohashi, Rei; Sakurai, Eriko; Toyomura, Fumimasa; Ueda, Yuri; Inoue, Shun; Tsukahara, Kiyoaki; Suzuki, Mamoru

2015-07-01

Surgical treatments for adductor spasmodic dysphonia include bilateral thyroarytenoid muscle myectomy (TAM) and type II thyroplasty (TPII), both of which are commonly performed. The present study aimed to compare the effects of TAM and TPII. Retrospective study. Subjects were 30 and 35 patients who underwent TAM and TPII, between March 2008 and November 2012. Voice quality was evaluated based on "voice handicap index 10 (VHI10)" and auditory impressions before and 6 months after surgery using five parameters: "strangulation," "interruption," "tremor," "grade," and "breathiness." Comparison of the two procedures revealed significant improvements in VHI10, strangulation, interruption, and tremor, and a significant decline in breathiness after surgery. In particular, VHI10 was improved by more than six points in 90% of patients with TAM, and 96% with TPII. No significant difference was observed between the severities of two procedures preoperatively. Comparison of each postoperative score between the two procedures revealed that TAM significantly improved strangulation, interruption, and tremor, and significantly worsened breathiness, with no significant difference in VHI10. Scatter plots (x: preoperative scores; y: postoperative scores) and regression lines of evaluation items demonstrated that TAM is more effective than TPII in severe cases. Compared with TPII, TAM tends to improve strangulation, interruption, and tremor; however, it tends to worsen breathiness postoperatively. Postoperative VHI10 scores did not differ significantly between the two procedures. Given favorable improvement rates, both surgical procedures were considered effective. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M., E-mail: ympatel@uncg.edu

2014-10-01

Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

International Nuclear Information System (INIS)

Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M.

2014-01-01

Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

Science.gov (United States)

Ahmed, Muhammad S.; Rainer, Carolyn; Nielsen, Sebastian R.; Quaranta, Valeria; Weyer-Czernilofsky, Ulrike; Engle, Danielle D.; Perez-Mancera, Pedro A.; Coupland, Sarah E.; Taktak, Azzam; Bogenrieder, Thomas; Tuveson, David A.; Campbell, Fiona; Schmid, Michael C.; Mielgo, Ainhoa

2017-01-01

Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. PMID:27742686

Trophically available metal - A variable feast

International Nuclear Information System (INIS)

Rainbow, Philip S.; Luoma, Samuel N.; Wang Wenxiong

2011-01-01

Assimilation of trace metals by predators from prey is affected by the physicochemical form of the accumulated metal in the prey, leading to the concept of a Trophically Available Metal (TAM) component in the food item definable in terms of particular subcellular fractions of accumulated metal. As originally defined TAM consists of soluble metal forms and metal associated with cell organelles, the combination of separated fractions which best explained particular results involving a decapod crustacean predator feeding on bivalve mollusc tissues. Unfortunately TAM as originally defined has subsequently frequently been used in the literature as an absolute description of that component of accumulated metal that is trophically available in all prey to all consumers. It is now clear that what is trophically available varies between food items, consumers and metals. TAM as originally defined should be seen as a useful starting hypothesis, not as a statement of fact. - Trophically Available Metal (TAM), the component of accumulated metal in food that is taken up by a feeding animal, varies with food type and consumer.

Trophically available metal - A variable feast

Energy Technology Data Exchange (ETDEWEB)

Rainbow, Philip S., E-mail: p.rainbow@nhm.ac.uk [Department of Zoology, Natural History Museum, Cromwell Rd, London SW7 5BD (United Kingdom); Luoma, Samuel N. [Department of Zoology, Natural History Museum, Cromwell Rd, London SW7 5BD (United Kingdom); John Muir Institute of the Environment, University of California, Davis, CA 95616 (United States); Wang Wenxiong [College of Marine and Environmental Sciences, State Key Laboratory for Marine Environmental Sciences, Xiamen University, Fujian (China)

2011-10-15

Assimilation of trace metals by predators from prey is affected by the physicochemical form of the accumulated metal in the prey, leading to the concept of a Trophically Available Metal (TAM) component in the food item definable in terms of particular subcellular fractions of accumulated metal. As originally defined TAM consists of soluble metal forms and metal associated with cell organelles, the combination of separated fractions which best explained particular results involving a decapod crustacean predator feeding on bivalve mollusc tissues. Unfortunately TAM as originally defined has subsequently frequently been used in the literature as an absolute description of that component of accumulated metal that is trophically available in all prey to all consumers. It is now clear that what is trophically available varies between food items, consumers and metals. TAM as originally defined should be seen as a useful starting hypothesis, not as a statement of fact. - Trophically Available Metal (TAM), the component of accumulated metal in food that is taken up by a feeding animal, varies with food type and consumer.

Differential induction of progestin-binding sites in uterine cell types by estrogen and antiestrogen

International Nuclear Information System (INIS)

Ennis, B.W.; Stumpf, W.E.

1988-01-01

Effects of antiestrogen on progestin binding in uterine cell types were determined and compared to those of estrogen. Effects on uterine morphology were also studied. Immature rats were treated with four daily sc injections of 100 micrograms hydroxytamoxifen [TAM(OH)], 5 micrograms estradiol (E2), or oil. On day 5 the rats were injected iv with 1 microgram of the synthetic progestin [ 3 H]Org 2058, and 1 h later uteri were excised, weighed, and processed for thaw-mount autoradiography. Treatment with TAM(OH) or E2 resulted in uterine weight gain, which was greater in animals treated with E2. E2 treatment resulted in cellular hypertrophy in all tissue compartments, especially in the luminal epithelium and myometrium, but TAM(OH) treatment resulted in hypertrophy of only the luminal epithelium. Treatment with TAM(OH) or E2 changed the pattern and intensity of nuclear binding of [ 3 H]Org 2058 from that in oil-treated controls. E2 increased progestin binding in stroma and myometrium and decreased it in luminal epithelium. TAM(OH), similarly, decreased progestin binding in the luminal epithelium and increased it, albeit less than E2, in the myometrium, but left it unchanged in the stroma. The results indicate that E2 and TAM(OH) differentially effect progestin binding among the uterine tissue compartments

Macrophage content of murine tumors: Associations with TD50 and tumor radiocurability

International Nuclear Information System (INIS)

Wike, J.; Hunter, N.; Volpe, J.; Milas, L.

1987-01-01

The experiments were designed to investigate whether the tumor-associated macrophage (TAM) content of murine solid tumors correlates with tumor response to ionizing radiation and with the clonogenic ability of tumor cells to establish s.c. tumors. Of 13 tumors studied, 6 were sarcomas and 7 were carcinomas; all tumors were of spontaneous origin in C/sub 3/Hf/Kam mice, with the exception of one sarcoma that was induced by 3-methylcholanthrene. Tumors were growing in the hind thighs of syngeneic mice, and their TAM content was determined when they were 8 mm in diameter. Their macrophage content varied greatly, ranging from 9 to 83%. Radiocurability of 8 mm tumors, determined by TCD50, ranged from 42 Gy (fibrosarcoma FSA) to > 80 Gy (hepatocarcinoma HCA-I). There was an obvious trend toward positive correlation (r = 0.43) between TAM content and reduced local tumor radiocurability. However, there was a significant negative correlation between TAM content and TD50 values, implying that cells from tumors with higher macrophage content were more clonogenic. TAM from the NFSA sarcoma, a tumor with a low TD50 value and poorly responsive to radiation, stimulated the in vitro growth of NFSA tumor cells. These observations suggest that high TAM content could be conducive to tumor cell proliferation and could be a factor in poor tumor radioresponse

Consolidated asset management for Minnesota local agencies.

Science.gov (United States)

2016-06-01

Transportation agencies are increasingly turning their attention to transportation asset management (TAM), a systematic process for tracking the conditions of physical infrastructure to make better decisions about its maintenance. TAM is mandated by ...

Tam tam in de polder: uitbreiding Afrikamuseum Berg en Dal door Rijksgebouwdienst

NARCIS (Netherlands)

Voorthuis, J.C.T.

2006-01-01

Op 27 mei dit jaar is in het glooiende boslandschap van Berg en Dal, vlak bij Nijmegen, de nieuwe uitbreiding van het Afrika Museum geopend. Het ontwerp is in vele opzichten voorbeeldig. Het stelt zich terughoudend op ten aanzien van zowel de schitterende omgeving als het doel - het tentoonstellen

8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis. Cell culture and murine model

Energy Technology Data Exchange (ETDEWEB)

Ryck, Tine de; Impe, Annouchka van; Bracke, Marc E. [Ghent University, Laboratory of Experimental Cancer Research, Department Radiation Oncology and Experimental Cancer Research, Ghent (Belgium); Vanhoecke, Barbara W. [Ghent University, Laboratory of Experimental Cancer Research, Department Radiation Oncology and Experimental Cancer Research, Ghent (Belgium); Ghent University, Laboratory of Microbial Ecology and Technology (LabMET), Ghent (Belgium); Heyerick, Arne [Ghent University, Laboratory of Pharmacognosy and Phytochemistry, Ghent (Belgium); Vakaet, Luc; Neve, Wilfried de [Ghent University Hospital, Department of Radiation Oncology, Ghent (Belgium); Mueller, Doreen [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); Schmidt, Margret [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); German Cancer Consortium (DKTK) partner site Dresden and German Cancer Center (DKFZ), Heidelberg (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Dresden (Germany); Medical University, Department of Radiation Oncology, CCC, and CD-Laboratory RadOnc, Vienna (Austria)

2015-05-01

The major component in the pathogenesis of oral radiation-induced mucositis is progressive epithelial hypoplasia and eventual ulceration. Irradiation inhibits cell proliferation, while cell loss at the surface continues. We conceived to slow down this desquamation by increasing intercellular adhesion, regulated by the E-cadherin/catenin complex. We investigated if 8-prenylnaringenin (8-PN) or tamoxifen (TAM) decrease the shedding of irradiated human buccal epithelial cells in vitro and thus delay the ulcerative phase of radiation-induced mucositis in vivo. In vitro, aggregates of buccal epithelial cells were irradiated and cultured in suspension for 11 days. 8-PN or TAM were investigated regarding their effect on cell shedding. In vivo, the lower tongue surface of mice was irradiated with graded single doses of 25 kV X-rays. The incidence, latency, and duration of the resulting mucosal ulcerations were analyzed after topical treatment with 8-PN, TAM or solvent. 8-PN or TAM prevented the volume reduction of the irradiated cell aggregates during the incubation period. This was the result of a higher residual cell number in the treated versus the untreated irradiated aggregates. In vivo, topical treatment with 8-PN or TAM significantly increased the latency of mucositis from 10.9 to 12.1 and 12.4 days respectively, while the ulcer incidence was unchanged. 8-PN and TAM prevent volume reduction of irradiated cell aggregates in suspension culture. In the tongues of mice, these compounds increase the latency period. This suggests a role for these compounds for the amelioration of radiation-induced mucositis in the treatment of head and neck tumors. (orig.) [German] Die wesentliche Komponente in der Pathogenese der radiogenen Mukositis ist eine progressive epitheliale Hypoplasie und letztendlich Ulzeration. Die Bestrahlung hemmt die Zellproliferation, waehrend der Zellverlust an der Oberflaeche fortbesteht. Wir versuchten, diese Desquamation durch eine Stimulation der

Implementation of transportation asset management in Grandview, Missouri : final report.

Science.gov (United States)

2017-02-01

The successful implementation of transportation asset management (TAM) by local governments facilitates the optimization of limited resources. The use of a data-driven TAM program helps to identify and prioritize needs, identify and dedicate resource...

Transportation asset management : a vehicle for mainstreaming ITS?

Science.gov (United States)

2001-06-01

This paper examines the use of transportation asset management (TAM) as a mechanism for mainstreaming" intelligent transportation systems (ITS) into the transportation decision-making process. TAM is an emerging set of tools and techniques that compr...

Linking climate suitability, spread rates and host-impact when estimating the potential costs of invasive pests.

Science.gov (United States)

Kriticos, Darren J; Leriche, Agathe; Palmer, David J; Cook, David C; Brockerhoff, Eckehard G; Stephens, Andréa E A; Watt, Michael S

2013-01-01

Biosecurity agencies need robust bioeconomic tools to help inform policy and allocate scarce management resources. They need to estimate the potential for each invasive alien species (IAS) to create negative impacts, so that relative and absolute comparisons can be made. Using pine processionary moth (Thaumetopoea pityocampa sensu lato) as an example, these needs were met by combining species niche modelling, dispersal modelling, host impact and economic modelling. Within its native range (the Mediterranean Basin and adjacent areas), T. pityocampa causes significant defoliation of pines and serious urticating injuries to humans. Such severe impacts overseas have fuelled concerns about its potential impacts, should it be introduced to New Zealand. A stochastic bioeconomic model was used to estimate the impact of PPM invasion in terms of pine production value lost due to a hypothetical invasion of New Zealand by T. pityocampa. The bioeconomic model combines a semi-mechanistic niche model to develop a climate-related damage function, a climate-related forest growth model, and a stochastic spread model to estimate the present value (PV) of an invasion. Simulated invasions indicate that Thaumetopoea pityocampa could reduce New Zealand's merchantable and total pine stem volume production by 30%, reducing forest production by between NZ$1,550 M to NZ$2,560 M if left untreated. Where T. pityocampa is controlled using aerial application of an insecticide, projected losses in PV were reduced, but still significant (NZ$30 M to NZ$2,210 M). The PV estimates were more sensitive to the efficacy of the spray program than the potential rate of spread of the moth. Our novel bioeconomic method provides a refined means of estimating potential impacts of invasive alien species, taking into account climatic effects on asset values, the potential for pest impacts, and pest spread rates.

Linking climate suitability, spread rates and host-impact when estimating the potential costs of invasive pests.

Directory of Open Access Journals (Sweden)

Darren J Kriticos

Full Text Available Biosecurity agencies need robust bioeconomic tools to help inform policy and allocate scarce management resources. They need to estimate the potential for each invasive alien species (IAS to create negative impacts, so that relative and absolute comparisons can be made. Using pine processionary moth (Thaumetopoea pityocampa sensu lato as an example, these needs were met by combining species niche modelling, dispersal modelling, host impact and economic modelling. Within its native range (the Mediterranean Basin and adjacent areas, T. pityocampa causes significant defoliation of pines and serious urticating injuries to humans. Such severe impacts overseas have fuelled concerns about its potential impacts, should it be introduced to New Zealand. A stochastic bioeconomic model was used to estimate the impact of PPM invasion in terms of pine production value lost due to a hypothetical invasion of New Zealand by T. pityocampa. The bioeconomic model combines a semi-mechanistic niche model to develop a climate-related damage function, a climate-related forest growth model, and a stochastic spread model to estimate the present value (PV of an invasion. Simulated invasions indicate that Thaumetopoea pityocampa could reduce New Zealand's merchantable and total pine stem volume production by 30%, reducing forest production by between NZ$1,550 M to NZ$2,560 M if left untreated. Where T. pityocampa is controlled using aerial application of an insecticide, projected losses in PV were reduced, but still significant (NZ$30 M to NZ$2,210 M. The PV estimates were more sensitive to the efficacy of the spray program than the potential rate of spread of the moth. Our novel bioeconomic method provides a refined means of estimating potential impacts of invasive alien species, taking into account climatic effects on asset values, the potential for pest impacts, and pest spread rates.

Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth

International Nuclear Information System (INIS)

Tsai, C.-S.; Chen, F.-H.; Wang, C.-C.; Huang, H.-L.; Jung, Shih-Ming; Wu, C.-J.; Lee, C.-C.; McBride, William H.; Chiang, C.-S.; Hong, J.-H.

2007-01-01

Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injecting them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo

Biopolymer mediated nanoparticles synthesized from Adenia hondala for enhanced tamoxifen drug delivery in breast cancer cell line

Science.gov (United States)

Varadharajaperumal, Pradeepa; Subramanian, Balakumar; Santhanam, Amutha

2017-09-01

Silver nanoparticles (AgNPs) are an important class of nanomaterials, which have used as antimicrobial and disinfectant agents due to their detrimental effect on target cells. In the present study it was explored to deliver a novel tamoxifen drug system that can be used in breast cancer treatment, based on chitosan coated silver nanoparticles on MCF-7 human breast cancer cells. AgNPs synthesized from Adenia hondala tuber extract were used to make the chitosan coated AgNPs (Ch-AgNPs), in which the drug tamoxifen was loaded on chitosan coated silver nanoparticles (Tam-Ch-AgNPs) to construct drug loaded nanoparticles as drug delivery system. The morphology and characteristics of the Ch-AgNPs were investigated by UV, FTIR, zeta potential and FESEM. Furthermore, the toxicity of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs was evaluated through cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase-3, DNA laddering, and TUNEL assay in human breast cancer cells (MCF-7) and HBL-100 continuous cell line as a control. Treatment of cancer cells with various concentrations of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs for 24 h revealed that Tam-Ch-AgNPs could inhibit cell viability and induce significant membrane leakage in a dose-dependent manner. Cells exposed to Tam-Ch-AgNPs showed increased reactive oxygen species and hydroxyl radical production when compared to AgNPs, Ch-AgNPs. Furthermore, the apoptotic effects of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs were confirmed by activation of caspase-3 and DNA nuclear fragmentation. The present findings suggest that Tam-Ch-AgNPs could contribute to the development of a suitable anticancer drug delivery.

High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis

Directory of Open Access Journals (Sweden)

Yuan ZY

2014-08-01

Full Text Available Zhong-Yu Yuan,1–3* Rong-Zhen Luo,1,2,4,* Rou-Jun Peng,1–3 Shu-Sen Wang,1–3 Cong Xue1–3 1State Key Laboratory of Oncology in South China, 2Collaborative Innovation Center for Cancer Medicine, 3Departments of Medical Oncology, Sun Yat-Sen University Cancer Center, 4Departments of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China  *These authors contributed equally to this work Background: Triple-negative breast cancer (TNBC is associated with poor prognosis and high probability of distant metastases. Tumor microenvironments play a pivotal role in tumor metastasis. Tumor-associated macrophages (TAMs are one of the main cell components, and they are correlated with increasing metastatic risk. The aim of this study is to analyze the prognostic significance of the infiltration of TAMs in patients with TNBC. Materials and methods: Immunohistochemical staining for cluster of differentiation (CD68 (a marker for macrophages was performed on tissue microarrays of operable breast cancer among 287 patients with TNBC, and the number of infiltrating TAMs was correlated with clinicopathological parameters. Results: We found that TNBC with a large number of infiltrating TAMs had a significantly higher risk of distant metastasis, as well as lower rates of disease-free survival and overall survival than those with a smaller number of infiltrating TAMs. Multivariate analysis indicated that the number of infiltrating TAMs was a significant independent prognostic factor of disease-free survival (P=0.001 in all patients. Conclusion: Our results suggested that high infiltrating TAMs are a significantly unfavorable prognostic factor for patients with TNBC, and they could become a potentially useful prognostic marker for TNBC. Keywords: breast carcinoma, triple-negative, tumor-associated macrophages, prognosis

Gender differences associated with enrollment in the Texas Academy of Mathematics and Science

Science.gov (United States)

Burns, Robert Thomas

This study sought to determine if different factors had influenced females and males to select engineering/science-related studies at the Texas Academy of Mathematics and Science (TAMS). The data were collected in the fall semester in 1997 at TAMS located on the University of North Texas campus from a survey of factors reported in the literature that had influenced students to enroll in engineering/science-related curriculum. Of the 380 TAMS students enrolled fall semester, 303 or 85% participated in the study. Those who participated included 135 or 45% females and 168 or 55% males. A dichotomous discriminant function analysis to identify relationships between the criterion variable (gender) and the predictor variable (factors) was used. The analysis of variance (ANOVA) was used to identify any significant predictor (factor) when the criterion was gender. Analysis of the data indicated no difference between females and males concerning factors that influenced them to enroll in TAMS. Neither discriminant function analysis nor the regression analysis using weighted least squares could significantly establish any relationship that could predict a student to be female or male with respect to factors that influenced them to enroll in TAMS. The factors were ranked utilizing the Thurstone equal appearing intervals scale for both females and males. Both females and males in TAMS ranked extrinsic interest including job opportunity, salary, and promotion, as the most important factor. The least important factor for both females and males was family encouragement. The findings indicate that TAMS students based their enrollment decision on factors independent of those suggested in the literature as applying to males and females. This may have resulted from the fact that these students are a unique population biased toward valuing a math/science curriculum.

The study of the influence of food supplement “Enzo Way 5.02” on the properties of bread and its microbiological indicators

Directory of Open Access Journals (Sweden)

V. V. Petrichenko

2017-01-01

Full Text Available In article results of research of influence of application of technological (TAM “Enzo Way 5.02” (limited liability company “grain Ingredient” while softening wheat on physical-chemical, structural-mechanical and microbiological indicators of bread from wheat flour first grade. It is established that the specific volume of the test sample (TAM was 10 cm3/100 g compared with reference sample (white bread from wheat flour first grade. Analysis of the results of humidity and acidity of bread has shown that TAM does not affect these parameters, however, the porosity in the experimental sample was 3% more than the control. The total deformation in the test specimen more by 24.4%, plastic deformation on 17%, elastic deformation by 40%, relative plastic deformation by 14%, relative elastic deformation at 12%, the coefficient of elasticity by 20.5%. The results of the analysis of microbiological indicators show that TAM “EnzoWay 5.02” reduces the number of bacteria in the bread of a test sample after 3 h after baking at 80% (almost 5 times, and after 72 h 92% (13 times, compared with white bread from wheat flour first grade. Thus the positive influence of using TAM “EnzoWay 5.02” while softening wheat on physical-chemical, structural-mechanical and microbiological indicators bread from wheat flour first grade. It is proved expediency of application of TAM in the production of flour and bakery products.

Monocytes/macrophages support mammary tumor invasivity by co-secreting lineage-specific EGFR ligands and a STAT3 activator

International Nuclear Information System (INIS)

Vlaicu, Philip; Mertins, Philipp; Mayr, Thomas; Widschwendter, Peter; Ataseven, Beyhan; Högel, Bernhard; Eiermann, Wolfgang; Knyazev, Pjotr; Ullrich, Axel

2013-01-01

Tumor-associated macrophages (TAM) promote malignant progression, yet the repertoire of oncogenic factors secreted by TAM has not been clearly defined. We sought to analyze which EGFR- and STAT3-activating factors are secreted by monocytes/macrophages exposed to tumor cell-secreted factors. Following exposure of primary human monocytes and macrophages to supernatants of a variety of tumor cell lines, we have analyzed transcript and secreted protein levels of EGFR family ligands and of STAT3 activators. To validate our findings, we have analyzed TAM infiltration levels, systemic and local protein levels as well as clinical data of primary breast cancer patients. Primary human monocytes and macrophages respond to tumor cell-derived factors by secreting EGFR- and STAT3-activating ligands, thus inducing two important oncogenic pathways in carcinoma cells. Tumor cell-secreted factors trigger two stereotype secretory profiles in peripheral blood monocytes and differentiated macrophages: monocytes secrete epiregulin (EREG) and oncostatin-M (OSM), while macrophages secrete heparin-binding EGF-like growth factor (HB-EGF) and OSM. HB-EGF and OSM cooperatively induce tumor cell chemotaxis. HB-EGF and OSM are co-expressed by TAM in breast carcinoma patients, and plasma levels of both ligands correlate strongly. Elevated HB-EGF levels accompany TAM infiltration, tumor growth and dissemination in patients with invasive disease. Our work identifies systemic markers for TAM involvement in cancer progression, with the potential to be developed into molecular targets in cancer therapy

Drug: D04496 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available oxifen derivative ... DG01620 ... Tamoxifene-type antineoplastic ... DG01621 ... Cloimifene-type osteoporosis agent ... Clomifene, tam... D04496 Drug Idoxifene (USAN/INN) ... C28H30INO D04496.gif ... Other ... DG01619 ... Clomifene and tam

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

International Nuclear Information System (INIS)

Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea.

Science.gov (United States)

Almendros, Isaac; Wang, Yang; Becker, Lev; Lennon, Frances E; Zheng, Jiamao; Coats, Brittney R; Schoenfelt, Kelly S; Carreras, Alba; Hakim, Fahed; Zhang, Shelley X; Farré, Ramon; Gozal, David

2014-03-01

An increased cancer aggressiveness and mortality have been recently reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, enhances melanoma growth and metastasis in mice. To assess whether OSA-related adverse cancer outcomes occur via IH-induced changes in host immune responses, namely tumor-associated macrophages (TAMs). Lung epithelial TC1 cell tumors were 84% greater in mice subjected to IH for 28 days compared with room air (RA). In addition, TAMs in IH-exposed tumors exhibited reductions in M1 polarity with a shift toward M2 protumoral phenotype. Although TAMs from tumors harvested from RA-exposed mice increased TC1 migration and extravasation, TAMs from IH-exposed mice markedly enhanced such effects and also promoted proliferative rates and invasiveness of TC1 cells. Proliferative rates of melanoma (B16F10) and TC1 cells exposed to IH either in single culture or in coculture with macrophages (RAW 264.7) increased only when RAW 264.7 macrophages were concurrently present. Our findings support the notion that IH-induced alterations in TAMs participate in the adverse cancer outcomes reported in OSA.

Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

Directory of Open Access Journals (Sweden)

Katharina Galmbacher

Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

DEFF Research Database (Denmark)

Yang, Yunlong; Andersson, Patrik; Hosaka, Kayoko

2016-01-01

Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33......-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological...... inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic...

Evidence-based decision making : developing a knowledge base for successful program outcomes in transportation asset management.

Science.gov (United States)

2015-12-01

MAP-21 and AASHTOs framework for transportation asset management (TAM) offer opportunities to use more : rigorous approaches to collect and apply evidence within a TAM context. This report documents the results of a study : funded by the Georgia D...

48 CFR 1201.105-2 - Arrangement of regulations.

Science.gov (United States)

2010-10-01

... chapter 12 will be cited by “FAR” followed by the FAR numbered cite, and cross reference to the TAM in (TAR) 48 CFR chapter 12 will be cited by “TAM” followed by the TAM numbered cite. References to...

Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

International Nuclear Information System (INIS)

Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

2012-01-01

Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

International Nuclear Information System (INIS)

Cimica, Velasco; Smith, Melissa E; Zhang, Zhikai; Mathur, Deepti; Mani, Sridhar; Kalpana, Ganjam V

2010-01-01

Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the concentration of flavopiridol needed for inhibition of RTs. The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii) caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA) analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G 2 arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G 2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G 2 arrest, but enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing caspase 2 and 3 activities. Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was enhanced by abrogation of p53. Our results warrant further

Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

Energy Technology Data Exchange (ETDEWEB)

Cimica, Velasco; Smith, Melissa E; Zhang, Zhikai; Mathur, Deepti [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Mani, Sridhar [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Kalpana, Ganjam V [Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States); Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)

2010-11-19

Rhabdoid Tumors (RTs) are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam) in order to reduce the concentration of flavopiridol needed for inhibition of RTs. The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i) cell survival assays, ii) FACS analysis, iii) caspase activity assays, and iv) immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA) analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G{sub 2} arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G{sub 2} arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G{sub 2} arrest, but enhanced flavopiridol- (but not 4OH-Tam-) mediated apoptosis, by enhancing caspase 2 and 3 activities. Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was enhanced by abrogation of p53. Our results

Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen

Directory of Open Access Journals (Sweden)

Mani Sridhar

2010-11-01

Full Text Available Abstract Background Rhabdoid Tumors (RTs are highly aggressive pediatric malignancies with poor prognosis. There are currently no standard or effective treatments for RTs in part because treatments are not designed to specifically target these tumors. Our previous studies indicated that targeting the cyclin/cdk pathway is a novel therapeutic strategy for RTs and that a pan-cdk inhibitor, flavopiridol, inhibits RT growth. Since the toxicities and narrow window of activity associated with flavopiridol may limit its clinical use, we tested the effect of combining flavopiridol with 4-hydroxy-Tamoxifen (4OH-Tam in order to reduce the concentration of flavopiridol needed for inhibition of RTs. Methods The effects of flavopiridol, 4OH-Tam, and their combination on RT cell cycle regulation and apoptosis were assessed by: i cell survival assays, ii FACS analysis, iii caspase activity assays, and iv immunoblot analysis. Furthermore, the role of p53 in flavopiridol- and 4OH-Tam-mediated induction of cell cycle arrest and apoptosis was characterized using RNA interference (siRNA analysis. The effect of p53 on flavopiridol-mediated induction of caspases 2, 3, 8 and 9 was also determined. Results We found that the combination of flavopiridol and 4OH-Tam potently inhibited the growth of RT cells. Low nanomolar concentrations of flavopiridol induced G2 arrest, which was correlated to down-modulation of cyclin B1 and up-regulation of p53. Addition of 4OH-Tam did not affect flavopiridol-mediated G2 arrest, but enhanced caspase 3,7-mediated apoptosis induced by the drug. Abrogation of p53 by siRNA abolished flavopiridol-induced G2 arrest, but enhanced flavopiridol- (but not 4OH-Tam- mediated apoptosis, by enhancing caspase 2 and 3 activities. Conclusions Combining flavopiridol with 4OH-Tam potently inhibited the growth of RT cells by increasing the ability of either drug alone to induce caspases 2 and 3 thereby causing apoptosis. The potency of flavopiridol was

[PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine granules for children at free drug concentrations in pediatric patients with respiratory infection].

Science.gov (United States)

Toyonaga, Yoshikiyo; Iwai, Naoichi; Motohiro, Takashi; Sunakawa, Keisuke; Fujii, Ryochi

2008-06-01

A post-marketing clinical study was previously conducted in pediatric patients with respiratory infection to evaluate the pharmacokinetics, efficacy and safety of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results from this study, we evaluated PK/PD breakpoints and clinical/bacteriological effects of CFPN-PI at free drug concentrations in pediatric patients with respiratory infection to determine an effective and safe dosage regimen of CFPN-PI. The following results were obtained from 61 pediatric patients evaluated in our research. 1) The response rate of pediatric respiratory infection to CFPN-PI was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The blood concentration simulation demonstrated that the PK/PD breakpoint exceeding the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or = 40% group) and 0% to 40% (TAM or = 40% group, and 88.9% and 62.5% in the TAM or = 40% group than in the TAM < 40% group, although the between-group difference was not statistically significant.

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

International Nuclear Information System (INIS)

Shigeoka, Manabu; Urakawa, Naoki; Nishio, Mari; Takase, Nobuhisa; Utsunomiya, Soken; Akiyama, Hiroaki; Kakeji, Yoshihiro; Komori, Takahide; Koma, Yu-ichiro; Yokozaki, Hiroshi

2015-01-01

Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

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Forgacs Agnes L

2009-04-01

Full Text Available Abstract Background Tamoxifen (TAM is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge. Results A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns. Conclusion Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.

Study of the difference in rectal and ear canal temperature according to the conformation of the acoustic conch in dogsEstudo da diferença das temperaturas retal e do canal auditivo de acordo com a conformação da concha acústica em cães

Directory of Open Access Journals (Sweden)

Eduardo Negri Mueller

2012-10-01

Full Text Available The auditory thermometry has being used for measurement of temperature of dogs. However there is different acoustic conch conformation in this species, being that the pendulous ears can alter the auditory microclimate. This research aimed to study the difference of rectal and auditory canal temperatures according to acoustic conch conformation in dogs. One hundred and eleven dogs were used with erect ears (group I, semi-pendulous (group II and pendulous (group II with 37 animals each group. The measurement of rectal temperature (TR was realized with traditional thermometer mercury column and measurement of both external ears temperature with infrared ear thermometer. The average hearing temperature (TAM was obtained and realized difference between TR and TAM, being the results classify in scores, A=TAMA termometria auditiva vem sendo utilizada para mensuração da temperatura em cães. Porém, existem diferentes conformações da concha acústica nesta espécie, sendo que orelhas pendulares podem alterar o microclima auditivo. Portanto, objetivou-se estudar a diferença das temperaturas retal e do canal auditivo de acordo com a conformação da concha acústica em cães. Foram utilizados 111 cães hígidos com orelhas ereta (grupo I, semipendular (grupo II e pendular (grupo III com 37 animais cada. A aferição da temperatura retal (TR foi realizada com termômetro tradicional coluna de mercúrio e aferição da temperatura de ambas as orelhas externas com termômetro auricular infravermelho. Foi obtida temperatura auditiva média (TAM e realizada diferença entre TR e TAM, sendo os resultados classificados em escores, A=TAMTAMTAM foi 37,15ºC±0,81, enquanto que a da TR foi 38,68ºC±0,59. A diferença média entre TAM e TR foi 1,53ºC±0,75. Setenta e uma orelhas (63,96% foram classificadas no escore B e 40 (36,04% no escore A. A média da TAM foi 37,17°C±0,85, 37,35°C±0,50 e 36

Degenerative Disease in an Aging Population Models and Conjectures

NARCIS (Netherlands)

J.J.M. Barendregt (Jan); L.G.A. Bonneux (Luc)

1998-01-01

textabstractThis PhD thesis is rootcd in a mnltidisciplinary project, ca lied Technology Assessment lvlethods (TAM). The (ambitious) aim of the TAM project was to develop a comprehcllsive method of evalnating medical tcchnology in the perspective of multiple risk factors, multiple diseascs and

Understanding technology adoption through individual and context characteristics: the case of HDTV

NARCIS (Netherlands)

Baaren, Eva; van de Wijngaert, Lidwien; Huizer, E.

2011-01-01

Technology adoption research has a tradition of using and improving Davis' (1989) “Technology Acceptance Model” (TAM) and extended versions of it. This article suggests a break with this tradition by showing that the TAM is limited in its understanding of technology adoption. Two alternative

Evaluation of the prognostic role of tumour-associated macrophages in newly diagnosed classical Hodgkin lymphoma and correlation with early FDG-PET assessment.

Science.gov (United States)

Cencini, Emanuele; Fabbri, Alberto; Rigacci, Luigi; Lazzi, Stefano; Gini, Guido; Cox, Maria Christina; Mancuso, Salvatrice; Abruzzese, Elisabetta; Kovalchuk, Sofia; Goteri, Gaia; Di Napoli, Arianna; Bono, Roberto; Fratoni, Stefano; Di Lollo, Simonetta; Bosi, Alberto; Leoncini, Lorenzo; Bocchia, Monica

2017-03-01

In Hodgkin Lymphoma (HL), about 20% of patients still have relapsed/refractory disease and late toxic effects rate continue to rise with time. 'Early FDG-PET' and tissue macrophage infiltration (TAM) emerged as powerful prognostic predictors. The primary endpoint was to investigate the prognostic role of both early FDG-PET and TAM; the secondary endpoint was to test if early FDG-PET positivity could correlate with high TAM score. A cohort of 200 HL patients was analysed. Induction treatment plan consisted of two to six courses of ABVD and, if indicated, involved field radiation therapy. All patients repeated CT scan and FDG-PET after two cycles and after the completion of therapy. TAM in diagnostic specimens was determined by immunohistochemistry with a monoclonal antibody (anti-CD68 KP1). Overall, early FDG-PET was negative in 163 patients (81.5%) and positive in 37 patients (18.5%), showing a significant correlation with the achievement of CR (p PET negative patients (p PET result. This study confirms that early FDG-PET has a high prognostic power, while TAM score does not seem to influence the outcome; in contrast to our original hypothesis, it does not correlate with FDG-PET assessment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Muscle changes in brachial plexus birth injury with elbow flexion contracture: an MRI study

Energy Technology Data Exchange (ETDEWEB)

Poeyhiae, Tiina H; Koivikko, Mika P; Lamminen, Antti E [University of Helsinki, Helsinki Medical Imaging Center, Helsinki (Finland); Peltonen, Jari I; Nietosvaara, A Y [Helsinki University Central Hospital, Hospital for Children and Adolescents, Helsinki (Finland); Kirjavainen, Mikko O [Helsinki University Central Hospital, Department of Orthopaedics and Traumatology, Helsinki (Finland)

2007-02-15

Muscle pathology of the arm and forearm in brachial plexus birth injury (BPBI) with elbow flexion contracture has not been evaluated with MRI. To determine whether limited range of motion of the elbow in BPBI is correlated with specific patterns of muscular pathology. For 15 BPBI patients, total active motion (TAM) of the elbow (extension-flexion) and the forearm (pronation-supination) were measured. MRI of the elbow joints and musculature allowed assessment of elbow congruency. Fatty infiltration and size reduction of the muscles were graded semiquantitatively. Mean TAM of the elbow was 113 (50 -140 ) and that of the forearm 91 (10 -165 ). The greater the size reduction of the brachioradialis muscle, the more diminished was elbow TAM. The more extensive the BPBI and muscle pathology of the pronator teres muscle, the more limited was the TAM of the forearm. Pathology of the supinator and brachialis muscles was evident in every patient. Extensive BPBI may result in marked limitation of TAM. Elbow flexion contracture seems to be caused mainly by brachialis muscle pathology. Prosupination of the forearm is better preserved when the pronator teres is not severely affected. MRI can reliably show the extent of muscle pathology in BPBI. (orig.)

High-capacity quantum key distribution via hyperentangled degrees of freedom

International Nuclear Information System (INIS)

Simon, David S; Sergienko, Alexander V

2014-01-01

Quantum key distribution (QKD) has long been a promising area for the application of quantum effects in solving real-world problems. However, two major obstacles have stood in the way of its widespread application: low secure key generation rates and short achievable operating distances. In this paper, a new physical mechanism for dealing with the first of these problems is proposed: the interplay between different degrees of freedom in a hyperentangled system (parametric down-conversion) is used to increase the Hilbert space dimension available for key generation while maintaining security. Polarization-based Bell tests provide security checking, while orbital angular momentum (OAM) and total angular momentum (TAM) provide a higher key generation rate. Whether to measure TAM or OAM is decided randomly in each trial. The concurrent noncommutativity of TAM with OAM and polarization provides the physical basis for quantum security. TAM measurements link polarization to OAM, so that if the legitimate participants measure OAM while the eavesdropper measures TAM (or vice-versa), then polarization entanglement is lost, revealing the eavesdropper. In contrast to other OAM-based QKD methods, complex active switching between OAM bases is not required; instead, passive switching by beam splitters combined with much simpler active switching between polarization bases makes implementation at high OAM more practical. (paper)

Muscle changes in brachial plexus birth injury with elbow flexion contracture: an MRI study

International Nuclear Information System (INIS)

Poeyhiae, Tiina H.; Koivikko, Mika P.; Lamminen, Antti E.; Peltonen, Jari I.; Nietosvaara, A.Y.; Kirjavainen, Mikko O.

2007-01-01

Muscle pathology of the arm and forearm in brachial plexus birth injury (BPBI) with elbow flexion contracture has not been evaluated with MRI. To determine whether limited range of motion of the elbow in BPBI is correlated with specific patterns of muscular pathology. For 15 BPBI patients, total active motion (TAM) of the elbow (extension-flexion) and the forearm (pronation-supination) were measured. MRI of the elbow joints and musculature allowed assessment of elbow congruency. Fatty infiltration and size reduction of the muscles were graded semiquantitatively. Mean TAM of the elbow was 113 (50 -140 ) and that of the forearm 91 (10 -165 ). The greater the size reduction of the brachioradialis muscle, the more diminished was elbow TAM. The more extensive the BPBI and muscle pathology of the pronator teres muscle, the more limited was the TAM of the forearm. Pathology of the supinator and brachialis muscles was evident in every patient. Extensive BPBI may result in marked limitation of TAM. Elbow flexion contracture seems to be caused mainly by brachialis muscle pathology. Prosupination of the forearm is better preserved when the pronator teres is not severely affected. MRI can reliably show the extent of muscle pathology in BPBI. (orig.)

The assessment of a novel electrical stimulation waveform recently introduced for the treatment of overactive bladder

International Nuclear Information System (INIS)

Slovak, M; Barker, A T; Chapple, C R

2013-01-01

Transdermal amplitude modulated signal (TAMS) is a novel electrical stimulus which has been recently introduced for the treatment of overactive bladder (OAB) syndrome. It has been suggested that it has advantages over conventional waveforms by providing more effective penetration of the skin to enhance the efficacy of therapy. As there is no literature which supports this, we performed this study to evaluate potential advantages of the TAMS signal for electrical stimulation of subcutaneous nerves as compared to conventional stimuli. The stimuli were applied on forearms of ten healthy volunteers and electrical parameters of stimuli and sensation measurements were recorded. None of the recorded electrical parameters showed significant differences (paired t-test p ≥ 0.250) between the TAMS and conventional waveforms. Similarly, the mean sensation recorded at motor threshold level and at 50% of maximal motor response level showed no differences (paired t-test p = 0.242 and p = 0.687 respectively). It is unlikely, based on the results of this study, that TAMS provides any enhancement of the efficacy of conventional stimuli. We would recommend that further studies are carried out to clearly demonstrate in man what, if any, advantages the TAMS waveform has over conventional stimulation before it is widely deployed into clinical practice. (paper)

Inhibition of MAP kinase promotes the recruitment of corepressor SMRT by tamoxifen-bound estrogen receptor alpha and potentiates tamoxifen action in MCF-7 cells

International Nuclear Information System (INIS)

Hong, Wei; Chen, Linfeng; Li, Juan; Yao, Zhi

2010-01-01

Estrogen receptor alpha (ERα), a ligand controlled transcription factor, plays an important role in breast cancer growth and endocrine therapy. Tamoxifen (TAM) antagonizes ERα activity and has been applied in breast cancer treatment. TAM-bound ERα associates with nuclear receptor-corepressors. Mitogen-activated protein kinase (MAPK) has been elucidated to result in cross-talk between growth factor and ERα mediated signaling. We show that activated MAPK represses interaction of TAM-bound ERα with silencing mediator for retinoid and thyroid hormone receptors (SMRT) and inhibits the recruitment of SMRT by ERα to certain estrogen target genes. Blockade of MAPK signaling cascade with MEK inhibitor U0126 promotes the interaction and subsequently inhibits ERα activity via enhanced recruitment of SMRT, leading to reduced expression of ERα target genes. The growth rate of MCF-7 cells was decelerated when treated with both TAM and U0126. Moreover, the growth of MCF-7 cells stably expressing SMRT showed a robust repression in the presence of TAM and U0126. These results suggest that activated MAPK signaling cascade attenuates antagonist-induced recruitment of SMRT to ERα, suggesting corepressor mediates inhibition of ERα transactivation and breast cancer cell growth by antagonist. Taken together, our finding indicates combination of antagonist and MAPK inhibitor could be a helpful approach for breast cancer therapy.

Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

Energy Technology Data Exchange (ETDEWEB)

Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

1988-01-01

We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Ke-Fei He

2014-01-01

Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

Bandwidth Analysis of Functional Interconnects Used as Test Access Mechanism

NARCIS (Netherlands)

Van den Berg, A.; Ren, P.; Marinissen, E.J.; Gaydadjiev, G.; Goossens, K.

2010-01-01

Test data travels through a System on Chip (SOC) from the chip pins to the Core-Under-Test (CUT) and vice versa via a Test Access Mechanism (TAM). Conventionally, a TAM is implemented using dedicated communication infrastructure. However, also existing functional interconnect, such as a bus or

Bandwidth analysis of functional interconnects used as test access mechanism

NARCIS (Netherlands)

Berg, van den Ardy; Ren, P.; Marinissen, Erik Jan; Gaydadjiev, G.N.; Goossens, K.G.W.

2010-01-01

Test data travels through a System on Chip (SOC) from the chip pins to the Core-Under-Test (CUT) and vice versa via a Test Access Mechanism (TAM). Conventionally, a TAM is implemented using dedicated communication infrastructure. However, also existing functional interconnect, such as a bus or

A meta-analysis of the technology acceptance model : investigating subjective norm and moderation effects

NARCIS (Netherlands)

Schepers, J.J.L.; Wetzels, M.G.M.

2007-01-01

We conducted a quantitative meta-analysis of previous research on the technology acceptance model (TAM) in an attempt to make well-grounded statements on the role of subjective norm. Furthermore, we compared TAM results by taking into account moderating effects of one individual-related factor (type

The acceptance and use of a virtual learning environment in China

NARCIS (Netherlands)

Raaij, van E.M.; Schepers, J.J.L.

2008-01-01

The success of a virtual learning environment (VLE) depends to a considerable extent on student acceptance and use of such an e-learning system. After critically assessing models of technology adoption, including the Technology Acceptance Model (TAM), TAM2, and the Unified Theory of Acceptance and

An Exploration of the Factors Influencing the Adoption of an IS Governance Framework

Science.gov (United States)

Parker, Sharon L.

2013-01-01

This research explored IT governance framework adoption, leveraging established IS theories. It applied both the technology acceptance model (TAM) and the technology, organization, environment (TOE) models. The study consisted of developing a model utilizing TOE and TAM, deriving relevant hypotheses. Interviews with a group of practitioners…

A study of the Teachers` Academy for Mathematics and Science

Energy Technology Data Exchange (ETDEWEB)

Brett, B.; Scheirer, M.A.; Raizen, S.

1994-09-15

The Teachers` Academy for Mathematics and Science in Chicago (TAMS) is a freestanding institution founded in 1989 by scientists and a variety of other stakeholders, to advance the systemic reform of mathematics and science education in Chicago`s public schools. It focuses on the ``re-tooling`` of its elementary level teachers. The TAMS program, which has been funded in part by the DOE, contributes to strategic goals two through five of the Office of University and Science Education (OUSE). This evaluation of TAMS by the National Center for Improving Science Education is primarily a qualitative study that summarizes the history and current status of the organization and its programs. Data was obtained through extensive interviews, observations, and document review, using a framework of templates to guide data collection and analyses. The findings are organized around a series of lessons learned from the first three years of TAMS and conclusions about its current status.

Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

Science.gov (United States)

Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

2014-01-01

Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

Science.gov (United States)

Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

2016-05-09

Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer.

The technology acceptance model: its past and its future in health care.

Science.gov (United States)

Holden, Richard J; Karsh, Ben-Tzion

2010-02-01

Increasing interest in end users' reactions to health information technology (IT) has elevated the importance of theories that predict and explain health IT acceptance and use. This paper reviews the application of one such theory, the Technology Acceptance Model (TAM), to health care. We reviewed 16 data sets analyzed in over 20 studies of clinicians using health IT for patient care. Studies differed greatly in samples and settings, health ITs studied, research models, relationships tested, and construct operationalization. Certain TAM relationships were consistently found to be significant, whereas others were inconsistent. Several key relationships were infrequently assessed. Findings show that TAM predicts a substantial portion of the use or acceptance of health IT, but that the theory may benefit from several additions and modifications. Aside from improved study quality, standardization, and theoretically motivated additions to the model, an important future direction for TAM is to adapt the model specifically to the health care context, using beliefs elicitation methods.

Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

Science.gov (United States)

Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

2017-09-26

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment

International Nuclear Information System (INIS)

Mori, Kazumasa; Haraguchi, Shigeki; Hiori, Miki; Shimada, Jun; Ohmori, Yoshihiro

2015-01-01

Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman’s rank analysis. An increase in the rate of CD163 + TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4 + Th cell infiltration. Although CCR4 + cells rarely infiltrated, CXCR3 + and CCR5 + cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163 + TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu

Anti-cancer Effect of Xao Tam Phan Paramignya trimera Methanol Root Extract on Human Breast Cancer Cell Line MCF-7 in 3D Model.

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Nguyen-Thi, Lam-Huyen; Nguyen, Sinh Truong; Tran, Thao Phuong; Phan-Lu, Chinh-Nhan; The Van, Trung; Van Pham, Phuc

2018-04-24

Cancer is one of the leading causes of death in the world. A great deal of effort has been made to discover new agents for cancer treatment. Xao tam phan (Paramignya trimera) is a traditional medicine of Vietnam used in cancer treatment for a long time, yet there is not much scientific evidence proving its anticancer potency. The study aimed to evaluate the toxicity of Paramignya trimera extract (PTE) on multicellular tumor spheres (MCTS) of MCF-7 cells using hanging drop technique. Firstly, MCF-7 cells were seeded on hanging drop plates, spheroid size was tracked, and growth curve was measured by MTT assay and AlamarBlue ® assay. The necrotic core of MCTS was evaluated by propidium iodide (PI) staining. Toxicity of doxorubicin (DOX) and tirapazamine (TPZ) was then tested on 3D model compared to 2D culture condition. The results showed that the IC50 of DOX on 3D MCF-7 cells was nearly 50 times greater than monolayer MCF-7 cells. In contrast, TPZ (an agent which is specifically toxic under hypoxic conditions) had significantly lower IC50 in 3D condition than in 2D. The toxicity tests for PTE showed that PTE strongly inhibited MCF-7 cells in both 2D and 3D conditions. Interestingly, the IC50 of PTE in 3D model was remarkably lower than in 2D (IC50 value was 168.9 ± 11.65 μg/ml compared to 260.8 ± 16.54 μg/ml, respectively). The invasion assay showed that PTE completely inhibited invasion of MCF-7 cells at 250 μg/mL concentration. Also, flow cytometry results indicated that PTE effectively induced apoptosis in MCF-7 spheroids in 3D condition at 250 μg/mL concentration. The results from this study emphasize the promise of PTE in cancer therapy.

Pre-Service Teachers' Attitude towards Information and Communication Technology Usage: A Ghanaian Survey

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Gyamfi, Stephen Adu

2017-01-01

This study employed the Technology Acceptance Model (TAM) to empirically investigate factors that influence Ghanaian pre-service teachers' attitudes towards Information and Communication Technology (ICT) usage. To achieve this aim, the study extended the TAM framework by adding leadership support and job relevance as exogenous variables. Data were…

Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems

NARCIS (Netherlands)

C. D'Oliveira; A. Feenstra; H.W. Vos (Helma); A.D.M.E. Osterhaus (Albert); B.R. Shiels; A.W.C.A. Cornelissen; F. Jongejan

1997-01-01

textabstractAllelic forms (Tams1-1 and Tams1-2) of the major merozoite surface antigen gene of Theileria annulata have recently been expressed in Escherichia coli and in Salmonella typhimurium aroA vaccine strain SL3261. To test the potential of subunit vaccines against T. annulata infection, we

The Role of Peer Influence and Perceived Quality of Teaching in Faculty Acceptance of Web-Based Learning Management Systems

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Salajan, Florin D.; Welch, Anita G.; Ray, Chris M.; Peterson, Claudette

2015-01-01

This study's primary investigation is the impact of "peer influence" and "perceived quality of teaching" on faculty members' usage of web-based learning management systems within the Technology Acceptance Model (TAM) framework. These factors are entered into an extended TAM as external variables impacting on the core constructs…

78 FR 46379 - Exelon Generation Company, LLC, License Renewal Application for Braidwood Station, Units 1 and 2

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2013-07-31

... Comments'' in the SUPPLEMENTARY INFORMATION section of this document. FOR FURTHER INFORMATION CONTACT: Tam... Commission, Washington, DC 20555-0001; telephone: 301-415-3617, email: Tam[email protected] . SUPPLEMENTARY...). Pursuant to 36 CFR 800.8(c), the NRC intends to use its process and documentation for the preparation of...

Análisis de cocitación de autor en el modelo de aceptación tecnológico, 2005-2010

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Córdoba-Cely, Carlos

2012-06-01

Full Text Available This paper explores the research trends of the Technology Acceptance Model (TAM using Author co-citation analysis (ACA methods, from January 2005 to June 2010. Through the ISI Web of Knowledge (WoK 38 key authors were selected: a Factor Analysis was performed and different techniques of information visualization, such as Multidimensional Scaling (MDS and Pathfinder Network (PFNET, were applied. The goal of this article is to identify the most popular research topics of TAM over the five years studied. The results obtained reveal two new research themes, as well as the existence of three constructs highlighted by researchers of TAM. The results are discussed.

Este artículo explora las tendencias de investigación en el Modelo de Aceptación Tecnológico (TAM a través del método de Análisis de Cocitación de Autor (ACA entre los anos 2005 y 2010. Por medio de la ISI Web of Knowledge (WoK se identificaron 38 autores claves sobre los cuales se realizó un Análisis Factorial y un análisis de redes Pathfinder. El objetivo de este documento es complementar estas técnicas de visualización de conocimiento para identificar los tópicos de investigación más populares en los últimos cinco años del TAM. Los resultados muestran la existencia de dos nuevos tópicos de investigación así como la existencia de tres constructos destacados por los investigadores del TAM. Se discuten los resultados obtenidos.

Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

International Nuclear Information System (INIS)

Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

2014-01-01

Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe 3 O 4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe 3 O 4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue. (papers)

Survival benefit of tamoxifen and aromatase inhibitor in male and female breast cancer.

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Eggemann, Holm; Altmann, Udo; Costa, Serban-Dan; Ignatov, Atanas

2018-02-01

Our goal was to compare the survival advantage of tamoxifen (TAM) and aromatase inhibitor (AI) in female (FBC) and male breast cancer (MBC). We performed a retrospective study of 2785 FBC and 257 MBC patients treated with hormonal therapy. The median follow-up was 106 months (range 3-151 months) and 42 months (range 2-115 months) for FBC and MBC, respectively. The patients were divided into two groups according to the hormonal therapy used: TAM-treated and AI-treated. MBC was characterized by older age, advanced tumor stage, and higher rate of lymph node metastases, in comparison with FBC. Matching analysis was performed using six prognostic criteria: patient age, tumor stage, tumor grade, lymph node status, human epidermal growth factor receptor (HER2) status, and administration of chemotherapy. The female and male patients were matched 2:1. In this analysis, 316 women and 158 men treated with TAM, and 60 women and 30 men treated with AI, were included. The overall survival (OS) was estimated by the Kaplan-Meier method and was compared between FBC and MBC. TAM-treated FBC and MBC patients had similar 5-year OS, 85.1 and 89.2%, respectively (p = 0.972). Notably, FBC patients treated with AI had significantly greater 5-year OS (85.0%) in comparison with AI-treated MBC patients (5-year OS of 73.3%; p = 0.028). The OS of TAM-treated patients with MBC was similar to the OS of TAM-treated FBC patients, whereas AI treatment is associated with poorer survival of MBC patients.

Initiative action of tumor-associated macrophage during tumor metastasis

Directory of Open Access Journals (Sweden)

Saroj Singh

2017-06-01

In this review article, we present an overview of mechanisms responsible for TAMs recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. We describe the interplay between Th17 cells and other immune cells in the tumor microenvironment, and we assess both the potential antitumorigenic and pro-tumorigenic activities of Th17 cells and their associated cytokines. Understanding the nature of Th17 cell responses in the tumor microenvironment will be important for the design of more efficacious cancer immunotherapies. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

International Nuclear Information System (INIS)

Moerkens, Marja; Zhang, Yinghui; Wester, Lynn; Water, Bob van de; Meerman, John HN

2014-01-01

Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10 -12 to 10 -6 M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK 1/3 , AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM

78 FR 73451 - Defense Federal Acquisition Regulation Supplement: Unallowable Fringe Benefit Costs (DFARS Case...

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2013-12-06

... contract. Penalties may be waived in accordance with FAR 42.709-5(c). 9. Exceeding the Actual Costs of... not face the possibility of False Claims Act prosecutions, Civil False Claims Act damages, qui tam... possibility of False Claims Act prosecutions, Civil False Claims Act damages, qui tam lawsuits or debarment...

48 CFR 1201.104 - Applicability.

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2010-10-01

... Transportation Acquisition Manual (TAM): (1) Statute; (2) (FAR) 48 CFR chapter 1 or other applicable regulation; (3) (TAR) 48 CFR chapter 12; (4) DOT Orders; and (5) TAM. (c) The Maritime Administration may depart....C. 113(e)(15) but shall adhere to those regulations to the maximum extent practicable. Exceptions...

Learning Computerese: The Role of Second Language Learning Aptitude in Technology Acceptance

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Warner, Janis A.; Koufteros, Xenophon; Verghese, Anto

2014-01-01

This article introduces a new construct coined as Computer User Learning Aptitude (CULA). To establish construct validity, CULA is embedded in a nomological network that extends the technology acceptance model (TAM). Specifically, CULA is posited to affect perceived usefulness and perceived ease of use, the two underlying TAM constructs.…

Applying the Extended Technology Acceptance Model to the Use of Clickers in Student Learning: Some Evidence from Macroeconomics Classes

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Wu, Xiaoyu; Gao, Yuan

2011-01-01

This paper applies the extended technology acceptance model (exTAM) in information systems research to the use of clickers in student learning. The technology acceptance model (TAM) posits that perceived ease of use and perceived usefulness of technology influence users' attitudes toward using and intention to use technology. Research subsequent…

Modelling the Intention to Use Technology for Teaching Mathematics among Pre-Service Teachers in Serbia

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Teo, Timothy; Milutinovic, Verica

2015-01-01

This study aims to examine the variables that influence Serbian pre-service teachers' intention to use technology to teach mathematics. Using the technology acceptance model (TAM) as the framework, we developed a research model to include subjective norm, knowledge of mathematics, and facilitating conditions as external variables to the TAM. In…

Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment

Science.gov (United States)

Finkernagel, Florian; Lieber, Sonja; Schnitzer, Evelyn; Legrand, Nathalie; Schober, Yvonne; Nockher, W. Andreas; Toth, Philipp M.; Diederich, Wibke E.; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf

2015-01-01

The nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor associated with macrophage polarization. However, its function in tumor-associated macrophages (TAMs) has not been investigated to date. Here, we report the PPARβ/δ-regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients. Comparison with monocyte-derived macrophages shows that the vast majority of direct PPARβ/δ target genes are upregulated in TAMs and largely refractory to synthetic agonists, but repressible by inverse agonists. Besides genes with metabolic functions, these include cell type-selective genes associated with immune regulation and tumor progression, e.g., LRP5, CD300A, MAP3K8 and ANGPTL4. This deregulation is not due to increased expression of PPARβ/δ or its enhanced recruitment to target genes. Instead, lipidomic analysis of malignancy-associated ascites revealed high concentrations of polyunsaturated fatty acids, in particular linoleic acid, acting as potent PPARβ/δ agonists in macrophages. These fatty acid ligands accumulate in lipid droplets in TAMs, thereby providing a reservoir of PPARβ/δ ligands. These observations suggest that the deregulation of PPARβ/δ target genes by ligands of the tumor microenvironment contributes to the pro-tumorigenic polarization of ovarian carcinoma TAMs. This conclusion is supported by the association of high ANGPTL4 expression with a shorter relapse-free survival in serous ovarian carcinoma. PMID:25968567

In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus

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Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo M.; Goya, Alejandra B.

2014-01-01

Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment. PMID:24936598

Onset and duration of ejaculatory suppression effect of tamsulosin in goat

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Sakdichod Kimsakulvech

2016-07-01

Full Text Available The duration of ejaculatory suppression of alpha adrenoceptor antagonist (tamsulosin, TAM was investigated in goats. Five males were injected intramuscularly with TAM 80 μg/kg (179.8 nmol/kg. Semen was collected using an artificial vagina with estrous female goats and the semen quality and libido score were evaluated at 1, 3, 6 and 9 h post TAM injection. Two replicates were carried out in the study. Heart rates were also measured before the injection and at 30 min before semen collection. The results showed that the libido score was not affected by TAM. At 1 h post injection, the highest percentage of suppressed ejaculation (80% was recorded and this effect was maintained for up to 3 h post injection (60%. Thereafter the percentage of suppressed ejaculation was significantly decreased (p < 0.05 at 6 h (20% and ejaculation was completely recovered at 9 h post injection. The semen characteristics of the collectable semen, semen volume and number of spermatozoa were lowest at 1 h and 3 h, thereafter they suddenly increased at 6 h and the significantly highest peak was noted at 9 h post injection. TAM injection suppressed goat ejaculation within 1 h and the duration was maintained up to 3 h post injection.

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

International Nuclear Information System (INIS)

Liguori, Manuela; Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola

2011-01-01

Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

Energy Technology Data Exchange (ETDEWEB)

Liguori, Manuela; Solinas, Graziella; Germano, Giovanni [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Mantovani, Alberto [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Department of Translational Medicine, University of Milano, Milano 20089 (Italy); Allavena, Paola, E-mail: paola.allavena@humanitasresearch.it [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy)

2011-09-28

Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

77 FR 30371 - Airworthiness Directives; International Aero Engines AG Turbofan Engines

Science.gov (United States)

2012-05-23

.... Request To Allow Special Flight Permits United Airlines and TAM Airlines requested that we allow Special... change the AD. Request To Delay USI Start Time and Repeat Inspection Time TAM Airlines requested that we....C. 106(g), 40113, 44701. Sec. 39.13 [Amended] 0 2. The FAA amends Sec. 39.13 by removing...

Perceived Convenience in an Extended Technology Acceptance Model: Mobile Technology and English Learning for College Students

Science.gov (United States)

Chang, Chi-Cheng; Yan, Chi-Fang; Tseng, Ju-Shih

2012-01-01

Since convenience is one of the features for mobile learning, does it affect attitude and intention of using mobile technology? The technology acceptance model (TAM), proposed by David (1989), was extended with perceived convenience in the present study. With regard to English language mobile learning, the variables in the extended TAM and its…

The Role of Voluntariness in Distance Education Students' Usage of a Course Website

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Ramayah, T.

2010-01-01

This study looks at the usage of a course website among distance learning business management students in a public institution of higher learning in Malaysia. The Technology Acceptance Model (TAM) was used as the basis of the research framework but voluntariness was added as a possible moderating factor. TAM postulates that perceived usefulness…

Understanding Which Residues of the Active Site and Loop Structure of a Tyrosine Aminomutase Define Its Mutase and Lyase Activities.

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Attanayake, Gayanthi; Walter, Tyler; Walker, Kevin D

2018-05-30

Site-directed mutations and substrate analogues were used to gain insights into the branch-point reaction of the 3,5-dihydro-5-methylidene-4 H-imidazol-4-one (MIO)-tyrosine aminomutase from Oryza sativa ( OsTAM). Exchanging the active residues of OsTAM (Y125C/N446K) for those in a phenylalanine aminomutase TcPAM altered its substrate specificity from tyrosine to phenylalanine. The aminomutase mechanism of OsTAM surprisingly changed almost exclusively to that of an ammonia lyase making cinnamic acid (>95%) over β-phenylalanine [Walter, T., et al. (2016) Biochemistry 55, 3497-3503]. We hypothesized that the missing electronics or sterics on the aryl ring of the phenylalanine substrate, compared with the sizable electron-donating hydroxyl of the natural tyrosine substrate, influenced the unexpected lyase reactivity of the OsTAM mutant. The double mutant was incubated with 16 α-phenylalanine substituent analogues of varying electronic strengths and sterics. The mutant converted each analogue principally to its acrylate with ∼50% conversion of the p-Br substrate, making only a small amount of the β-amino acid. The inner loop structure over the entrance to the active site was also mutated to assess how the lyase and mutase activities are affected. An OsTAM loop mutant, matching the loop residues of TcPAM, still chiefly made >95% of the acrylate from each substrate. A combined active site:loop mutant was most reactive but remained a lyase, making 10-fold more acrylates than other mutants did. While mutations within the active site changed the substrate specificity of OsTAM, continued exploration is needed to fully understand the interplay among the inner loop, the substrate, and the active site in defining the mutase and lyase activities.

Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

International Nuclear Information System (INIS)

Waalkes, Michael P.; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

2006-01-01

Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 μg/pup/day) or tamoxifen (TAM; 10 μg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-α, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES

Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

Science.gov (United States)

Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

2013-08-01

The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

Erratum: Correction to: The effects of the calcium-magnesium-bicarbonate content in thermal mineral water on chronic low back pain: a randomized, controlled follow-up study

Science.gov (United States)

Gáti, Tamás; Tefner, Ildikó Katalin; Kovács, Lajos; Hodosi, Katalin; Bender, Tamás

2018-05-01

The original article mistakenly displays each set of author names in the wrong order, i.e., first names as last names and vice versa. The author correct names are: Tamás Gáti, Ildikó Katalin Tefner, Lajos Kovács, Katalin Hodosi, Tamás Bender. The original article has been corrected.

User Acceptance of Social Learning Systems in Higher Education: An Application of the Extended Technology Acceptance Model

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Akman, Ibrahim; Turhan, Cigdem

2017-01-01

This study aims to explore the users' behaviour and acceptance of social media for learning in higher educational institutions with the help of the extended Technology Acceptance Model (TAM). TAM has been extended to investigate how ethical and security awareness of users affect the actual usage of social learning applications. For this purpose, a…

Correction to: The effects of the calcium-magnesium-bicarbonate content in thermal mineral water on chronic low back pain: a randomized, controlled follow-up study

Science.gov (United States)

Gáti, Tamás; Tefner, Ildikó Katalin; Kovács, Lajos; Hodosi, Katalin; Bender, Tamás

2018-02-01

The original article mistakenly displays each set of author names in the wrong order, i.e., first names as last names and vice versa. The author correct names are: Tamás Gáti, Ildikó Katalin Tefner, Lajos Kovács, Katalin Hodosi, Tamás Bender. The original article has been corrected.

Lactate - A new frontier in the immunology and therapy of prostate cancer.

Science.gov (United States)

Nenu, Iuliana; Gafencu, Grigore-Aristide; Popescu, Tiberiu; Kacso, Gabriel

2017-01-01

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.

Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Tarek K. Motawi

2016-01-01

Full Text Available Although Tamoxifen (TAM is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

Baczoni, Tamás, Tibor Balla et al. eds. 2014. A Nagy Háború, 1914-1918 - kézzelfogható hadtörténelem (The Great War, 1914-1918 - Tangible Military History]. Budapest: Zrínyi Kiadó, Honvédelmi Minisztérium Hadtörténeti Intézet és Múzeum munkatársai (Staff of the Institute and Museum of Military History Ministry of Defense. 68 pp. Two DVDs and fifty-six reproduced documentary inserts.

Directory of Open Access Journals (Sweden)

George Deák

2017-09-01

Full Text Available Baczoni, Tamás, Tibor Balla et al. eds. 2014. A Nagy Háború, 1914-1918 - kézzelfogható hadtörténelem (The Great War, 1914-1918 - Tangible Military History]. Budapest: Zrínyi Kiadó, Honvédelmi Minisztérium Hadtörténeti Intézet és Múzeum munkatársai (Staff of the Institute and Museum of Military History Ministry of Defense. 68 pp. Two DVDs and fifty-six reproduced documentary inserts.

Transient abnormal myelopoesis in an infant with Down syndrome

African Journals Online (AJOL)

2010-01-13

Jan 13, 2010 ... syndrome and trisomy 21 mosaicism (1). The majorities of infants with TAM are asymptomatic and picked up incidentally on routine testing. Most cases of TAM resolve over the first few months of life, but 13Á33% may go on to develop AML within the first four years of life. Neonates with Down syndrome are ...

Dutasteride plus tamsulosin fixed-dose combination first-line therapy versus tamsulosin monotherapy in the treatment of benign prostatic hyperplasia: a budget impact analysis in the Greek healthcare setting.

Science.gov (United States)

Geitona, Maria; Karabela, Pinelopi; Katsoulis, Ioannis A; Kousoulakou, Hara; Lyberopoulou, Eleni; Bitros, Eleftherios; Xaplanteris, Loukas; Papanicolaou, Sotiria

2014-09-26

The purpose of this study was to explore the budget impact of dutasteride plus tamsulosin fixed-dose combination (DUT + TAM FDC) versus tamsulosin monotherapy, in the treatment of patients with benign prostatic hyperplasia (BPH) from the perspective of the Greek healthcare insurance system. A Microsoft Excel-based model was developed to estimate the financial consequences of adopting DUT + TAM FDC within the Greek healthcare setting. The model, compared six mutually exclusive health states in two alternative treatment options: current standard of care and the introduction of DUT + TAM FDC in the market. The model used clinical inputs from the CombAT study; data on resource use associated with the management of BPH in Greece were derived from expert panel, and unit cost data were derived from official reimbursement tariffs. A payer perspective was taken into account. As patient distribution data between public and private sectors are not available in Greece two scenarios were investigated, considering the whole eligible population in each scenario. A 4 year time horizon was taken into account and included treatment costs, number of transurethral resections of the prostate (TURPs) and acute urinary retention (AUR) episodes avoided. The clinical benefit from the market adoption of DUT + TAM FDC in Greece was 1,758 TURPs and 972 episodes of AUR avoided cumulatively in a four year period. The increase in total costs from the gradual introduction of DUT + TAM FDC to the Greek healthcare system ranges from €1.3 million in the first year to €5.8 million in the fourth year, for the public sector, and €1.2 million to €4.0 million, for the private sector. This represents an increase of 1.91% to 7.94% for the public sector and 1.10% 3.29% in the private sector, during the 4-year time horizon. Budget impact analysis (BIA) results indicated that the gradual introduction of DUT + TAM FDC, would increase the overall budget of the disease, however providing

Anomaly depth detection in trans-admittance mammography: a formula independent of anomaly size or admittivity contrast

International Nuclear Information System (INIS)

Zhang, Tingting; Lee, Eunjung; Seo, Jin Keun

2014-01-01

Trans-admittance mammography (TAM) is a bioimpedance technique for breast cancer detection. It is based on the comparison of tissue conductivity: cancerous tissue is identified by its higher conductivity in comparison with the surrounding normal tissue. In TAM, the breast is compressed between two electrical plates (in a similar architecture to x-ray mammography). The bottom plate has many sensing point electrodes that provide two-dimensional images (trans-admittance maps) that are induced by voltage differences between the two plates. Multi-frequency admittance data (Neumann data) are measured over the range 50 Hz–500 kHz. TAM aims to determine the location and size of any anomaly from the multi-frequency admittance data. Various anomaly detection algorithms can be used to process TAM data to determine the transverse positions of anomalies. However, existing methods cannot reliably determine the depth or size of an anomaly. Breast cancer detection using TAM would be improved if the depth or size of an anomaly could also be estimated, properties that are independent of the admittivity contrast. A formula is proposed here that can estimate the depth of an anomaly independent of its size and the admittivity contrast. This depth estimation can also be used to derive an estimation of the size of the anomaly. The proposed estimations are verified rigorously under a simplified model. Numerical simulation shows that the proposed method also works well in general settings. (paper)

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas.

Science.gov (United States)

Li, Yan; He, Hai; Jia, Xinru; Lu, Wan-Liang; Lou, Jinning; Wei, Yen

2012-05-01

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

Science.gov (United States)

Netea-Maier, Romana T; Smit, Johannes W A; Netea, Mihai G

2018-01-28

In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Justifying a Set of Basic Characteristics of High Temperature Cold Accumulators in Their Designing for the Ground-Based Systems

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E. S. Khromov

2015-01-01

Full Text Available The ground-based systems use a wide variety of heat-emitting equipment. For temperature control of equipment and facilities, the thermal management systems (TMS are included in the ground-based systems. However, in operation, the off-nominal situations with increased heat emission are possible. To avoid overheating of equipment or environment in facilities, where equipment is placed, is possible through completing a set of TMS by high-temperature cold accumulators (CA.When filling CA by thermal accumulating materials (TAM with change in phase at the temperature level exceeding the ambient temperature, CA integration in TMS is simplified and the need to increase the cooling capacity of the sources of its cold is eliminated. Among the known multiple-cycle TAMs with change in phase "melting-solidification" in a set of characteristics, the most promising are crystal hydrates of salts and their systems, as well as paraffin, especially clean. However, advantages and disadvantages of these classes of TAM are different and disable us to develop a generic version of the CA design.The objective of this work is to identify a set of the main characteristics that significantly affect the CA efficiency. To achieve the goal is used a mathematical simulation of heat exchange and phase change processes, using CA with intermediate coolant as an example. Simulation is based on generation and solution of the system of equations of a thermal balance for the coolant circulating through the inner tube of CA container. The system of equations is solved using Excel tools.Varying values of studied characteristics and generalization of results allowed to us define a following set: TAM thermal conductivity, temperature difference in the coolant – TAM system, TAM container dimensions. The results can be applied when developing a CA, as a part of the "TMS-CA heat generation facility" of the ground-based systems with a specified heat absorption capacity at given temperature

Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy.

Science.gov (United States)

Shchors, Ksenya; Persson, Anders I; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S; Hanahan, Douglas; Weiss, William A; Evan, Gerard I

2013-04-16

Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRas(V12) mouse model crossed into the p53ER(TAM) background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ER(TAM) allele. The p53ER(TAM) protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRas(V12);p53(+/KI) mice abrogate the p53 pathway by mutating p19(ARF)/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ER(TAM) allele. By contrast, gliomas arising in GFAP-HRas(V12);p53(KI/KI) mice develop in the absence of functional p53. Such tumors retain a functional p19(ARF)/MDM2-signaling pathway, and restoration of p53ER(TAM) allele triggers p53-tumor-suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14(ARF)/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRas(V12);p53(KI/KI) animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ER(TAM) activity mitigated the selective pressure to inactivate the p19(ARF)/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance.

Integrative analysis of miRNA and gene expression reveals regulatory networks in tamoxifen-resistant breast cancer

DEFF Research Database (Denmark)

Joshi, Tejal; Elias, Daniel; Stenvang, Jan

2016-01-01

and 14-3-3 family genes. Integrating the inferred miRNA-target relationships, we investigated the functional importance of 2 central genes, SNAI2 and FYN, which showed increased expression in TamR cells, while their corresponding regulatory miRNA were downregulated. Using specific chemical inhibitors......Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer, however, tamoxifen resistance is frequently observed. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA......-mediated gene regulation in three clinically-relevant tamoxifen-resistant breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all Tam...

The Use of a Mobile Learning Management System at an Online University and Its Effect on Learning Satisfaction and Achievement

OpenAIRE

Won Sug Shin; Minseok Kang

2015-01-01

This study investigates online students’ acceptance of mobile learning and its influence on learning achievement using an information system success and extended technology acceptance model (TAM). Structural equation modeling was used to test the structure of individual, social, and systemic factors influencing mobile learning’s acceptance, and how said acceptance influences learning satisfaction and achievement. Unlike earlier TAM-related research that did not provide a broad view of technol...

Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

DEFF Research Database (Denmark)

Brünner, N; Yee, D; Kern, F G

1993-01-01

xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay......-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)...

Tendencia en la mortalidad por fiebre reumática aguda y cardiopatía reumática crónica en Venezuela, 1955-1994

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Isaacura César

1998-01-01

Full Text Available Este estudio incluye defunciones por fiebre reumática aguda (FRA y cardiopatía reumática crónica (CRC registradas en Venezuela de 1955 a 1994, según edad y sexo. Se calcularon tasas de mortalidad por 100.000 habitantes, ajustadas según método directo a la población mundial estándar de la OMS. Se produjo un descenso en la tasa ajustada de mortalidad (TAM por FR para ambos sexos de 7,68 a 1,08 (Variación Porcentual [VP] -85,9%; sexo masculino de 7,53 a 0,84 (VP -88,8% y sexo femenino de 7,83 a 1,33 (VP -83,0%. Las TAM fueron mayores en el sexo femenino. La proporción de muertes por FR sobre las producidas por enfermedades circulatorias (CIE-6 330-334,400-447; CIE-7 330-334,400-447; CIE-8 390-438; CIE-9 390-438 descendió en 88,5%. Se observó, para ambos sexos, un descenso en las TAM por FRA (VP -93,5% y CRC (VP -85,1%. El porcentaje de defunciones por FRA y CRC ocurridas en menores de 45 años mostró una tendencia ascendente. La reducción en las TAM por FR puede ser atribuible a mejoras socioeconómicas, así como a prevención con penicilina. La estabilización en las TAM a partir de 1980 podría explicarse por el deterioro socioeconómico experimentado en Venezuela y por la aparición de cepas más virulentas del EBHA.

Molecular dynamics simulation and binding free energy studies of novel leads belonging to the benzofuran class inhibitors of Mycobacterium tuberculosis Polyketide Synthase 13.

Science.gov (United States)

Cruz, Jorddy N; Costa, José F S; Khayat, André S; Kuca, Kamil; Barros, Carlos A L; Neto, A M J C

2018-05-04

In this work, the binding mechanism of new Polyketide Synthase 13 (Pks13) inhibitors has been studied through molecular dynamics simulation and free energy calculations. The drug Tam1 and its analogs, belonging to the benzofuran class, were submitted to 100 ns simulations, and according to the results obtained for root mean square deviation, all the simulations converged from approximately 30 ns. For the analysis of backbone flotation, the root mean square fluctuations were plotted for the Cα atoms; analysis revealed that the greatest fluctuation occurred in the residues that are part of the protein lid domain. The binding free energy value (ΔG bind ) obtained for the Tam16 lead molecule was of -51.43 kcal/mol. When comparing this result with the ΔG bind values for the remaining analogs, the drug Tam16 was found to be the highest ranked: this result is in agreement with the experimental results obtained by Aggarwal and collaborators, where it was verified that the IC 50 for Tam16 is the smallest necessary to inhibit the Pks13 (IC 50  = 0.19 μM). The energy decomposition analysis suggested that the residues which most interact with inhibitors are: Ser1636, Tyr1637, Asn1640, Ala1667, Phe1670, and Tyr1674, from which the greatest energy contribution to Phe1670 was particularly notable. For the lead molecule Tam16, a hydrogen bond with the hydroxyl of the phenol not observed in the other analogs induced a more stable molecular structure. Aggarwal and colleagues reported this hydrogen bonding as being responsible for the stability of the molecule, optimizing its physic-chemical, toxicological, and pharmacokinetic properties.

Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity

Energy Technology Data Exchange (ETDEWEB)

Tarlani, Aliakbar, E-mail: Tarlani@ccerci.ac.ir [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Narimani, Khashayar [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Mohammadipanah, Fatemeh; Hamedi, Javad [Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran 14155-6455 (Iran, Islamic Republic of); University of Tehran Biocompound Collection (UTBC), Microbial Technology and Products Research Center, University of Tehran, Tehran (Iran, Islamic Republic of); Tahermansouri, Hasan [Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol (Iran, Islamic Republic of); Amini, Mostafa M. [Department of Chemistry, Shahid Behshti University, 1983963113, Tehran (Iran, Islamic Republic of)

2015-06-30

Graphical abstract: In an antibacterial test, grafted copper(II) macrocyclic complex on the surface of MWCNT showed higher antibacterial activity against Bacillus subtilis compared to the individual MWCNT-COOH and the complex. - Highlights: • Copper(II) tetraaza macrocyclic complex covalently bonded to modified MWCNT. • Grafting of the complex carried out via an interaction between −C(=O)Cl group and NH of the ligand. • The samples were subjected in an antibacterial assessment to compare their activity. • Immobilized complex showed higher antibacterial activity against Bacillus subtilis ATCC 6633 compared to separately MWCNT-C(C=O)-OH and CuTAM. - Abstract: In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the I{sub D}/I{sub G} ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.

Spectrophotometric determination of yttrium with 2-(2-thiazolylazo)-5-dimethylaminophenol

International Nuclear Information System (INIS)

Tsurumi, Chikao; Furuya, Keiichi.

1975-01-01

Spectrophotometric determination of small amounts of yttrium with 2-(2-thiazolylazo)-5-dimethylaminophenol (TAM) in the presence of zephiramine was investigated. The recommended procedures were as follows; 2.0 ml of water, 7.0 ml of TAM-methanolic solution (2x10 -4 mol/l) and 2.0 ml of zephiramine-aqueous solution (1x10 -2 mol/l) were added to a solution containing less than 35 μg of yttrium and its pH was adjusted to 8.0 with 0.1 mol/l ammonium chloride-0.1 mol/l ammonium hydroxide solution. The solution was transferred to a 25 ml volumetric flask and diluted to the mark with water. After 20 minutes, the absorbance at 575 nm against a reagent blank was measured. The color of yttrium-TAM complex is reddish-violet in the presence of zephiramine and is stable for 90 minutes after color development. The yttrium-TAM complex shows an absorption maximum at 575 nm. The absorbance at 575 nm is constant in a pH range from 7.5 to 8.3. The molar extinction coefficient at this wavelength is 7.2x10 4 l.mol -1 .cm -1 . The band obeys Beer's law up to the concentration of 1.4 μg/ml of yttrium. The molar ratio of yttrium to TAM in the complex is 1 : 2. A number of ions interfere with the determination can be masked by the addition of various masking agents and removed in terms of trioctylamine-xylene extraction. Manganese, tantalum, tin(II), citrate and tartrate ions interfere with the determination. (auth.)

Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

Science.gov (United States)

McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

2017-07-01

Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

Efficacy and safety of tamsulosin hydrochloride 0.2 mg and combination of tamsulosin hydrochloride 0.2 mg plus solifenacin succinate 5 mg after transurethral resection of the prostate: a prospective, randomized controlled trial

Science.gov (United States)

Shin, Yu Seob; Zhang, Li Tao; You, Jae Hyung; Choi, In Sung; Zhao, Chen; Park, Jong Kwan

2016-01-01

Objective The objective of this study was to evaluate the safety and efficacy of tamsulosin hydrochloride 0.2 mg (TAM) and its combination with solifenacin succinate 5 mg (SOL) after transurethral resection of the prostate (TURP). Patients and methods The patients were randomized into three groups: TURP (group 1), TURP plus TAM (group 2), and TURP plus TAM + SOL (group 3). Patients in group 2 and group 3 received medication for 4 weeks. The primary efficacy end points were the mean change in total International Prostate Symptom Score (IPSS) and IPSS subscores. The secondary end points included quality-of-life score, Overactive Bladder Symptom Score, and short-form voiding and storage score of International Continence Society. Results In total, 37 men (31.8%) in group 1, 37 men (31.8%) in group 2, and 42 men (36.2%) in group 3 completed the study. In total IPSS, no significant improvement was seen from baseline to the end of treatment in groups 2 and 3 compared with group 1. However, in group 2, the decrement in the IPSS storage score was smaller than group 1 (P=0.02), and in group 3, the decrement in the IPSS voiding score was smaller than group 1 (P=0.05). In groups 2 and 3 compared with group 1, improvements in the quality of life score, total score of Overactive Bladder Symptom Score, and short-form voiding score and storage score of International Continence Society were not statistically significant. Conclusion Treatment with TAM and combination of TAM and SOL did not have significant additional benefits for lower urinary tract symptoms during the early recovery period after TURP. PMID:27698559

AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

International Nuclear Information System (INIS)

Zhao Wenhui; Zhang Qingyuan; Kang Xinmei; Jin Shi; Lou Changjie

2009-01-01

Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host.

Science.gov (United States)

Rai, Rakesh K; Vishvakarma, Naveen K; Mohapatra, Tribhuban M; Singh, Sukh Mahendra

2012-09-01

This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-β in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state. Bone marrow cell of Listeria-administered tumor-bearing mice showed augmented survival, declined expression of p53 upregulated modulator of apoptosis with an upregulated differentiation into activation responsive bone marrow-derived macrophages along with altered expression of macrophage-colony stimulating factor, macrophage-colony stimulating factor receptor, and granulocyte macrophage-colony stimulating factor receptor. These findings indicate that Listeria infection is associated with an augmented differentiation of macrophages accompanied by tumoricidal activation of TAM.

Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization.

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Chen, Xin; Ying, Xiang; Wang, Xinjing; Wu, Xiaoli; Zhu, Qinyi; Wang, Xipeng

2017-07-01

Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear. Herein, we demonstrated that hypoxia induces the high expression of microRNA-940 (miR‑940) in exosomes derived from epithelial ovarian cancer (EOC). We also found that miR‑940 is highly expressed in exosomes isolated from ascites of EOC patients. Moreover, the overexpression of miR‑940 in macrophages delivered by exosomes stimulated M2 phenotype polarization, while the M2 subtype macrophages promoted EOC proliferation and migration. These results highlight the function of hypoxia in enhancing the high level of expression of miR‑940 in tumor exosomes taken up by macrophages. We also showed that the tumor-promoting function of miR‑940 is mediated by TAM polarization in EOC. These findings show that tumor-derived exosomal miR‑940 induced by hypoxia plays an important role in stimulating TAM polarization in the progression of EOC.

Establishment of a Model of Microencapsulated SGC7901 Human Gastric Carcinoma Cells Cocultured with Tumor-Associated Macrophages

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Jin-Ming Zhu

2018-01-01

Full Text Available The important factors of poor survival of gastric cancer (GC are relapse and metastasis. For further elucidation of the mechanism, a culture system mimicking the microenvironment of the tumor in humans was needed. We established a model of microencapsulated SGC7901 human GC cells and evaluated the effects of coculturing spheres with tumor-associated macrophages (TAMs. SGC7901 cells were encapsulated in alginate-polylysine-sodium alginate (APA microcapsules using an electrostatic droplet generator. MTT assays showed that the numbers of microencapsulated cells were the highest after culturing for 14 days. Metabolic curves showed consumption of glucose and production of lactic acid by day 20. Immunocytochemistry confirmed that Proliferating Cell Nuclear Antigen (PCNA and Vascular Endothelial Growth Factor (VEGF were expressed in microencapsulated SGC7901 cells on days 7 and 14. The expression of PCNA was observed outside spheroids; however, VEGF was found in the entire spheroids. PCNA and VEGF were increased after being cocultured with TAMs. Matrix metalloproteinase-2 (MMP-2 and matrix metalloproteinase-9 (MMP-9 expressions were detected in the supernatant of microencapsulated cells cocultured with TAMs but not in microencapsulated cells. Our study confirms the successful establishment of the microencapsulated GC cells. TAMs can promote PCNA, VEGF, MMP-2, and MMP-9 expressions of the GC cells.

Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

OpenAIRE

Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

2011-01-01

Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages pro...

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

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Hiscox Stephen

2012-10-01

Full Text Available Abstract Background Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. Methods CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression or MCF7 cells (± transfection with the CD44 gene were treated with the CD44 ligand, hyaluronon (HA, or heregulin and their in vitro growth (MTT, migration (Boyden chamber and wound healing and invasion (Matrigel transwell migration determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. Results TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

International Nuclear Information System (INIS)

Hiscox, Stephen; Gee, Julia; Baruha, Bedanta; Smith, Chris; Bellerby, Rebecca; Goddard, Lindy; Jordan, Nicola; Poghosyan, Zaruhi; Nicholson, Robert I; Barrett-Lee, Peter

2012-01-01

Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration

Prospective comparison of breast pain in patients participating in a randomized trial of breast-conserving surgery and tamoxifen with or without radiotherapy

International Nuclear Information System (INIS)

Rayan, Gamal; Dawson, Laura A.; Bezjak, Andrea; Lau, Anthea; Fyles, Anthony W.; Yi, Q.-L.; Merante, Pat; Vallis, Katherine A.

2003-01-01

Purpose: To determine whether breast pain affects quality of life (QOL) after breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast radiotherapy (RT). Methods and Materials: A randomized clinical trial was carried out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need for breast RT in addition to TAM in women ≥50 years treated with breast-conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast pain was carried out during the last 2 years of the randomized clinical trial. The short-form McGill Pain Questionnaire (SF-MPQ), the European Organization for Research and Treatment of Cancer (EORTC) QOL (QLQ-C30) and EORTC breast cancer module (QLQ-BR23) questionnaires were completed by patients within 1 week of randomization in the randomized clinical trial (baseline) and at 3, 6, and 12 months. Results: Eighty-six patients participated in the breast pain study; 41 received RT plus TAM and 45 received TAM alone. The median age was 70 years (range 51-80). The baseline pain and QOL scores were similar for the two groups. No significant difference was found between the two groups for each scale of the QLQ-C30 and QLQ-BR23 questionnaires at 3, 6, or 12 months (p>0.100), except that at 12 months, the score for role function (QLQ-C30) was higher in the RT plus TAM group than in the RT-only group (p=0.02). At 3 months, the difference between the mean scores for the SF-MPQ was 0.553 (p=0.47). At 12 months, the pain scores had decreased in both groups; the difference was 0.199 (p=0.71). The number of breast operations or surgical complications did not correlate with breast pain in either group. Acute RT toxicity scores did not correlate with breast pain or QOL scores at 12 months. Conclusion: These results suggest that breast RT does not significantly contribute to breast pain or adversely impact the QOL up to 12 months after treatment in postmenopausal patients with node-negative breast cancer who take

Factors Influencing E-district Adoption: An Empirical Assessment in Indian Context

OpenAIRE

Baishya, Kuldeep; Samalia, Harsh Vardhan; Joshi, Rohit

2017-01-01

The purpose of this confirmatory study is to explore the factors influencing the acceptance of e-district services by the citizens inAssam, a North-East state of India. Taking unified theory of acceptance and use of technology (UTAUT), technology acceptance model (TAM) and TAM 3 as the basis, a conceptual framework is developed. The study uses semi-structured interviews, focus groups, and a questionnaire based survey through 166 valid data points to validate the conceptual framework. Moreover...

The Role of Tumor Associated Macrophage in Recurrent Growth of Tumor Stem Cell

Science.gov (United States)

2011-09-01

recent cancer stem cell (CSC) theory, recurrent tumor must arise from a dormant tumor stem cell whose re-growth is triggered by shifting of...microenvironment. This project aims at clarifying the roles of TAM in recurrent growth of dormant stem cell in breast cancer. We hypothesize that the balance of...dormancy and recurrence is determined by the ability of the tumor stem cells to recruit TAM which in turn promotes self-renewal of the stem cell . We

Evaluation of the Acceptance of Audience Response System by Corporations Using the Technology Acceptance Model

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Chu, Hsing-Hui; Lu, Ta-Jung; Wann, Jong-Wen

The purpose of this research is to explore enterprises' acceptance of Audience Response System (ARS) using Technology Acceptance Model (TAM). The findings show that (1) IT characteristics and facilitating conditions could be external variables of TAM. (2) The degree of E-business has positive significant correlation with behavioral intention of employees. (3) TAM is a good model to predict and explain IT acceptance. (4) Demographic variables, industry and firm characteristics have no significant correlation with ARS acceptance. The results provide useful information to managers and ARS providers that (1) ARS providers should focus more on creating different usages to enhance interactivity and employees' using intention. (2) Managers should pay attention to build sound internal facilitating conditions for introducing IT. (3) According to the degree of E-business, managers should set up strategic stages of introducing IT. (4) Providers should increase product promotion and also leverage academic and government to promote ARS.

The use of induced mutation combined with crossing in high quality rice breeding

International Nuclear Information System (INIS)

Do Huu At; Bui Huy Thuy; Nguyen Van Bich; Tran Duy Quy; Nguyen Minh Cong

2001-01-01

The high quality rice varieties: Tam thom mutant rice Var., DT17 rice Var, DT21 glutinous rice Var were formed by induced mutation combined with crossing. Tam thom mutant rice Var. lost photosensitivity, could be planted 2 crops/year. DT17 rice Var with high yielding capacity, suitable for growth on lowland in summer crop, is replacing step-by-step Moctuyen rice Var. in North Vietnam. DT21 glutinous rice Var. could be planted 2 crops/year and had short growth duration, average yield was 4.0-4.5 tons/ha. These three ones had good quality, soft and scent cooked rice, suitable for customers and export requirements. Tam thom mutant rice Var. DT17 rice Var., DT21 and glutinous rice Var. were adopted for regional production by Ministry of Agriculture and Rural Development and allowed to be in trial production. (author)

The use of induced mutation combined with crossing in high quality rice breeding

Energy Technology Data Exchange (ETDEWEB)

Do Huu At; Bui Huy Thuy; Nguyen Van Bich; Tran Duy Quy [Agricultural Genetics Institute, Division of Genetics and Hybrid Rice Technology, Hanoi (Viet Nam); Nguyen Minh Cong [Hanoi No. 1 Teacher Training Univ., Department of Genetics (Viet Nam)

2001-03-01

The high quality rice varieties: Tam thom mutant rice Var., DT17 rice Var, DT21 glutinous rice Var were formed by induced mutation combined with crossing. Tam thom mutant rice Var. lost photosensitivity, could be planted 2 crops/year. DT17 rice Var with high yielding capacity, suitable for growth on lowland in summer crop, is replacing step-by-step Moctuyen rice Var. in North Vietnam. DT21 glutinous rice Var. could be planted 2 crops/year and had short growth duration, average yield was 4.0-4.5 tons/ha. These three ones had good quality, soft and scent cooked rice, suitable for customers and export requirements. Tam thom mutant rice Var. DT17 rice Var., DT21 and glutinous rice Var. were adopted for regional production by Ministry of Agriculture and Rural Development and allowed to be in trial production. (author)

A Preliminary Introduction to the OTAM: Exploring Users’ Perceptions of their on-going Interaction with Adopted Technologies

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Shirlee-ann Knight

2011-03-01

Full Text Available ABSTRACT A common criticism directed at Davis’ (1986; 1989 Technology Acceptance Model relates to its failure to adequately frame the “experienced” user’s ongoing adoption and exploitation of information technologies. Given the pervasive nature of technology into individual users’ ongoing, everyday communication and information interactions, along with the “new adopter” becoming an increasingly rare entity, the TAM is in danger of becoming a somewhat obsolete framework for investigating user-technology interaction. Presented is a critical analysis of the development and current state of the TAM, followed by a proposed addition to the existing Perceived Usefulness (PU and Perceived Ease of Use (PEoU TAM constructs. The paper contends that the inclusion of a Perception of Interaction (PoI construct allows researchers to develop an investigative framework which facilitates an exploration of users’ ongoing perceptions of the predictability of their technology interaction processes.

Students’ Perceptions About Learning Environment of a Distance Course Based on Technology Acceptance Model: A Descriptive Study

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Erman UZUN

2013-03-01

Full Text Available Technology Acceptance Model (TAM is a measure to assess the underlying reasons about the use of a technology. In this study an extended version of TAM were used. This extended version composed of three factors. These are “perceived motivation towards learning environment”, “perceived usefulness” and “perceived ease of use”. In this study, the learning environment of a distance course was investigated to see students’ perceptions. This distance course was delivered from one university to the other university via video-conferencing with ITL Learning Gateway content management system during the whole semester. The participants were the 32 first year vocational higher education institution students. The descriptive findings revealed that each factor of TAM perceived by students as having moderate advantages. It is believed that the underlying reason of this situation was based on the students’ low computer competency and e-learning experiences.

Control of the molecular density in a chemically adsorbed thiophene system monolayer

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Tanaka Yosuke

2013-08-01

Full Text Available Chemically absorbed monolayers (CAM of thienyl functionalized n-alkyltrichlorosilane 11-(3-thienyl undecyltrichlorosilane (TUTS have been prepared with two methods which are the standard technique (TUTS-STD and the twice adsorption method (TUTS-TAM. The existence of TUTS-CAM was confirmed with water contact angle measurements, calculation of thickness with ellipsometry, fourier transform infrared reflection adsorption spectroscopy (FTIR-RAS. Here are described is the comparison of TUTS-STD and TUTS-TAM characterized by using Electron Spectroscopy for Chemical Analysis (ESCA and ultraviolet visible (UV-vis absorption spectroscopy. TUTS-TAM showed more densely packing than TUTS-STD by these measurements. Moreover, these TUTS-CAM polymerized by chemical oxidative polymerization and UV-Vis absorption spectra was measured to confirm the conjugated bond length of the polymerized thienyl groups. UV-vis spectra of the polymerized TUTS-CAM showed a new broad absorbance band at longer wavelength than 700nm.

INTENTION TO PURCHASE VIA THE INTERNET: A COMPARISON OF TWO THEORETICAL MODELS

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Jasman J. Ma'ruf

2005-01-01

Full Text Available This study compares two models for predicting intention to purchase via the Internet. The behavioral intention to purchase via the Internet was examined as a function of attitude towards purchase, perceived usefulness, and perceived ease of use Technology Acceptance Model (TAM, or attitude towards purchase, subjective norm, and perceived risk (Theory of Planned Behavior [TPB]. Results indicate that both models significantly influenced behavioral intention to purchase. We compared both models, and found that TPB (adjusted R2 = 0.55 is better than TAM (0.44 in explaining behavioral intention to purchase (BI. After we integrated TAM and TPB, we found that perceived risk (β = –0.332 is the primary determinant of BI, with subjective norm (SN (β = 0.210 as the significant secondary determinant, followed by attitude (A towards purchase (β = 0.175, perceived usefulness (β = 0.159, and perceived ease of use (β = 0.069.

Remediation of surface water polluted by effluent discharges from mining activities in the Eastern Region of Ghana

International Nuclear Information System (INIS)

Kusi, Samuel

2017-07-01

Heavy metals are very toxic to the environment and humans at large. Exposures to heavy metals have significant health disorders. In this research, the mandate to find novel adsorbent to reduce lead and mercury concentrations from water samples from Birim River in the Eastern Region of Ghana was studied. The turbidity of the water samples from Kibi, Anyinam and Kade indicated that, the river is very turbid (an average of 355 NTU) and therefore not recommended for domestic use without treatment. The modification of rice husk and orange peels with tartaric acid showed that modified rice husk had better binding efficiency for Pb and Hg. A series of batch experiments using tartaric acid modified rice husk (RH-TAM), tartaric acid orange peel modified (OP-TAM), unmodified rice husk (UM-RH) and unmodified orange peel (UM-OP) for the removal of Pb and Hg showed that the sorption processes depended on pH, contact time and adsorbent dosage. A pH of 5 with 0.5 g/20 ml of adsorbent solution maintained at a temperature of 35 o C ± 2 for a period of four (4) hours yielded the highest adsorption efficiency for both modified and unmodified adsorbents. The adsorption efficiencies recorded for RH –TAM and UM-RH were 75. 56 % and 69.93 % respectively for Pb. Similarly, Hg adsorption efficiencies for both RH-TAM and UM-RH were 53. 26 % and 45.11 % respectively. The adsorption efficiencies of OP –TAM was 62.03 % for Pb and 44.57% for Hg. The unmodified orange peel (UM-OP) had the least adsorption efficiencies of 51.88 % for Pb and 42.39% for Hg. The Langmuir isotherm fitted the experimental data for Pb and Hg better than the Freundlich isotherm. (author)

Fundamental investigation on influence of external heat on chip formation during thermal assisted machining

Science.gov (United States)

Alkali, A. U.; Ginta, T. L.; Abdulrani, A. M.; Elsiti, N. M.

2018-04-01

Various heat sources have been investigated by numerous researchers to reveal machinability benefits of thermally assisted machining (TAM) process. Fewer engineering materials have been tested. In the same vein, those researches continue to demonstrate effective performance of TAM in terms of bulk material removal rate, improved surface finish, prolong tool life and reduction of cutting forces among others. Experimental investigation on the strain-hardenability and flow stress of material removed with respect to increase in temperature in TAM has not been given attention in previous studies. This study investigated the pattern of chip morphology and segmentation giving close attention to influence of external heat source responsible for strain – hardenability of the material removed during TAM and dry machining at room temperature. Full immersion down cut milling was used throughout the machining conditions. Machining was conducted on AISI 316L using uncoated tungsten carbide end mill insert at varying cutting speeds (V) of 50, 79, and 100 m/min, and feed rates (f) of 0.15, 0.25, and 0.4 mm/tooth while the depth of cut was maintained at 0.2mm throughout the machining trials. The analyses of chip formation, segmentations and stain hardenability were carried out by using LMU light microscope, field emission microscopy and micro indentation. The study observed that build up edge is formed when a stagnation zone develops in front of tool tip which give rise to poor thermal gradient for conduction heat to be transferred within the bulk material during dry machining. This promotes varying strain – hardening of the material removed with evident high chips hardness and thickness, whereas TAM circumvents such impairment by softening the shear zone through local preheat.

Development of a health information technology acceptance model using consumers' health behavior intention.

Science.gov (United States)

Kim, Jeongeun; Park, Hyeoun-Ae

2012-10-01

For effective health promotion using health information technology (HIT), it is mandatory that health consumers have the behavioral intention to measure, store, and manage their own health data. Understanding health consumers' intention and behavior is needed to develop and implement effective and efficient strategies. To develop and verify the extended Technology Acceptance Model (TAM) in health care by describing health consumers' behavioral intention of using HIT. This study used a cross-sectional descriptive correlational design. We extended TAM by adding more antecedents and mediating variables to enhance the model's explanatory power and to make it more applicable to health consumers' behavioral intention. Additional antecedents and mediating variables were added to the hypothetical model, based on their theoretical relevance, from the Health Belief Model and theory of planned behavior, along with the TAM. We undertook structural equation analysis to examine the specific nature of the relationship involved in understanding consumers' use of HIT. Study participants were 728 members recruited from three Internet health portals in Korea. Data were collected by a Web-based survey using a structured self-administered questionnaire. The overall fitness indices for the model developed in this study indicated an acceptable fit of the model. All path coefficients were statistically significant. This study showed that perceived threat, perceived usefulness, and perceived ease of use significantly affected health consumers' attitude and behavioral intention. Health consumers' health status, health belief and concerns, subjective norm, HIT characteristics, and HIT self-efficacy had a strong indirect impact on attitude and behavioral intention through the mediators of perceived threat, perceived usefulness, and perceived ease of use. An extended TAM in the HIT arena was found to be valid to describe health consumers' behavioral intention. We categorized the concepts in

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

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Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

2014-01-01

First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

Tamoxifen is a potent antioxidant modulator for sperm quality in patients with idiopathic oligoasthenospermia.

Science.gov (United States)

Guo, Li; Jing, Jun; Feng, Yu-Ming; Yao, Bing

2015-09-01

To explore the new mechanisms of tamoxifen (TAM) in the treatment for patients with idiopathic oligoasthenospermia-antioxidation. In a prospective, randomized, controlled clinical trial, 120 cases of idiopathic oligoasthenospermia were enrolled and randomly assigned to the indomethacin group (n = 60) treated with indomethacin (25 mg, bid) and TAM group (n = 60) treated with TAM (10 mg, bid) for 3 months. Before and after treatment, we evaluated semen parameters, serum malondialdehyde (MDA) and total antioxidant capacity (TAC), seminal plasma MDA and TAC, spermatozoa intracellular reactive oxygen species (ROS), sperm succinate dehydrogenase (SDH) activity, sperm mitochondrial membrane potential (MMP), and sperm adenosine triphosphate (ATP) content. The independent t test and one-way repeated measures analysis of variance were used to compare the variables between and within two groups. In the indomethacin group, the percentage of progressive motile sperms, total motility, sperm MMP, and ATP content were increased significantly after 3-month treatment (P sperm count, sperm concentration, the percentage of progressive motile sperms, total motility, serum and seminal plasma TAC, sperm MMP, and ATP content were significantly improved or increased (P sperm count, sperm concentration, serum TAC, seminal plasma TAC, spermatozoa intracellular ROS, and sperm SDH activity. TAM treatment can significantly improve sperm quality, which is achieved through alleviating oxidative stress, improving sperm mitochondrial functionality, and subsequently increasing sperm motility.

Effect of long-term treatment with steroid hormones or tamoxifen on the progesterone receptor and androgen receptor in the endometrium of ovariectomized cynomolgus macaques

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Cline J Mark

2003-02-01

Full Text Available Abstract The progesterone receptor (PR and androgen receptor (AR belong to the nuclear receptor superfamily. Two isoforms of PR (A and B have been identified with different functions. The expression of AR, each isoform of PR and their involvement in long-term effects on the endometrium after hormonal replacement therapy (HRT or tamoxifen (TAM treatment is not known. The aims of this study were to determine PR(A+B, PRB and AR distribution by immunohistochemistry in the macaque (Macaca fascicularis endometrium. Ovariectomized (OVX animals were orally treated continuously for 35 months with either conjugated equine estrogens (CEE; medroxyprogesterone acetate (MPA; the combination of CEE/MPA; or TAM. Treatment with CEE/MPA tended to down-regulate PR in the superficial glands, but increased it in the stroma. TAM treatment increased both the PR and PRB levels in the stroma. Overall, less than 20% of the cells were positive for the PRB isoform and less variation was observed after steroid treatment. AR was found in the stroma, mainly distributed in the basal layer of the endometrium in the OVX and steroid treated groups, but was absent in the TAM treated group. No AR was found in the glandular epithelium. The present data show that long-term hormone treatment affects the PR level, and also the ratio between PRA and PRB in the endometrium.

Postmastectomy irradiation in high-risk breast cancer patients

International Nuclear Information System (INIS)

Overgaard, M.; Juul Christensen, J.; Johansen, H.; Nybo-Rasmussen, A.; Brincker, H.; Kooy, P. van der; Frederiksen, P.L.; Laursen, F.; Panduro, J.; Soerensen, N.E.; Gadeberg, C.C.; Hjelm-Hansen, M.; Overgaard, J.; West Andersen, K.; Zedeler, K.

1988-01-01

All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation+CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF+TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation+TAM, TAM or CMF+TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival. (orig.)

Continuous monitoring of plutonium solution in a conversion plant

International Nuclear Information System (INIS)

Hassan, B.; Piana, M.; Mousalli, G.; Saukkonen, H.; Hosima, T.; Kawa, T.

2000-01-01

This paper describes the implementation of a safeguards Tank Monitoring System (TAMS) in a Plutonium Conversion Plant (PCP). TAMS main objective is to provide the International Atomic Energy Agency (IAEA) (the Agency) with continuous data for safeguards evaluation and review of inventories and flows of plutonium solutions. It has been designed to monitor, in unattended mode, the inventory of each tank and transactions of solutions between tanks, as well as to confirm the absence of borrowing plutonium solutions from and to a neighboring reprocessing plant. The instrumentation consists of one electronic scanner that collects pressure data from electromanometers connected to the tank dip tubes, one uninterruptable power supply and one personal computer operating in a Windows-NT environment. The pressure data transmitted to the acquisition system is saved and converted to volume and density values, coupled with a graph capability to display events in each tank at intervals of 15 seconds. The system operation has not only strengthened the safeguards measures in PCP but also reduced inspection effort while minimizing intrusion to normal plant activities and radiation exposure to personnel. TAMS is a powerful, reliable tool that has significantly improved the effectiveness of safeguards implementation at PCP. The future combined use of TAMS with remote monitoring (RM) will further enhance efficiency of the safeguards measures at PCP. (author)

Transmission acoustic microscopy investigation

Science.gov (United States)

Maev, Roman; Kolosov, Oleg; Levin, Vadim; Lobkis, Oleg

The nature of acoustic contrast, i.e. the connection of the amplitude and phase of the output signal of the acoustic microscope with the local values of the acoustic parameters of the sample (density, elasticity, viscosity) is a central problem of acoustic microscopy. A considerable number of studies have been devoted to the formation of the output signal of the reflection scanning acoustic microscope. For the transmission acoustic microscope (TAM) this problem has remained almost unstudied. Experimental investigation of the confocal system of the TAM was carried out on an independently manufactured laboratory mockup of the TAM with the working frequency of the 420 MHz. Acoustic lenses with the radius of curvature of about 500 microns and aperture angle of 45 deg were polished out in the end faces of two cylindrical sound conductors made from Al2O3 single crystals with an axis parallel to the axis C of the crystal (the length of the sound conductor is 20 mm; diameter, 6 mm). At the end faces of the sound conductor, opposite to the lenses, CdS transducers with a diameter of 2 mm were disposed. The electric channel of the TAM provided a possibility for registering the amplitude of the microscope output signal in the case of the dynamic range of the 50 dB.

A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships.

Science.gov (United States)

Pucci, Ferdinando; Venneri, Mary Anna; Biziato, Daniela; Nonis, Alessandro; Moi, Davide; Sica, Antonio; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele

2009-07-23

We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1(+)Cd11b(+) neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction-based gene arrays. TEMs sharply differed from ECs and Gr1(+)Cd11b(+) cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2(+) embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be co-opted by tumors.

Potentials of Local Economic Development in Aspect of Tourism

OpenAIRE

Viktória Csizmadiáné Czuppon; Edina Sáriné Csajka; Tamás Molnár

2015-01-01

The objective of the study is to introduce the potentials of local economic development in one of the least favoured micro regions, Tamási. The paper examines operating and planned activities at settlements of the micro region. The authors introduce local economic development activities that support tourism. The economic development planning in Tamási micro region has typically two directions. One of them is the utilisation of thermal water and the use of further potentials of the thermal bat...

A Conceptual Model of eLearning Adoption

Directory of Open Access Journals (Sweden)

Muneer Abbad

2011-05-01

Full Text Available Internet-based learning systems are being used in many universities and firms but their adoption requires a solid understanding of the user acceptance processes. The technology acceptance model (TAM has been used to test the acceptance of various technologies and software within an e-learning context. This research aims to discuss the main factors of a successful e-learning adoption by students. A conceptual research framework of e-learning adoption is proposed based on the TAM model.

Matching methods to produce maps for pest risk analysis to resources

Directory of Open Access Journals (Sweden)

Richard Baker

2013-09-01

Full Text Available Decision support systems (DSSs for pest risk mapping are invaluable for guiding pest risk analysts seeking to add maps to pest risk analyses (PRAs. Maps can help identify the area of potential establishment, the area at highest risk and the endangered area for alien plant pests. However, the production of detailed pest risk maps may require considerable time and resources and it is important to match the methods employed to the priority, time and detail required. In this paper, we apply PRATIQUE DSSs to Phytophthora austrocedrae, a pathogen of the Cupressaceae, Thaumetopoea pityocampa, the pine processionary moth, Drosophila suzukii, spotted wing Drosophila, and Thaumatotibia leucotreta, the false codling moth. We demonstrate that complex pest risk maps are not always a high priority and suggest that simple methods may be used to determine the geographic variation in relative risks posed by invasive alien species within an area of concern.

Inhibition of CSF-1R supports T-cell mediated melanoma therapy.

Directory of Open Access Journals (Sweden)

Marjolein Sluijter

Full Text Available Tumor associated macrophages (TAM can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+ myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNγ production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors.

Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice

DEFF Research Database (Denmark)

Brünner, N; Bronzert, D; Vindeløv, L L

1989-01-01

The effects of estradiol and tamoxifen (TAM) on the estrogen-dependent human breast cancer cell line MCF-7 grown in vitro and in nude mice were compared. The effect on growth was determined by cell number in vitro and by tumor growth curves in nude mice. The effects on the cell cycle kinetics were...... determined by repeated flow cytometric DNA analyses in vitro and in vivo and by the technique of labeled mitosis in nude mouse-grown tumors. Under in vitro conditions, estradiol induced a pronounced increase in S-phase fraction and cell number. TAM inhibited growth of MCF-7 cells with a concomitant increase...... in the G1 phase from 60% to 75%. In nude mice, MCF-7 only formed tumors in estradiol-supplemented mice. No differences were observed in growth and cell kinetics between 0.1 and 1.0 mg of estradiol. Daily i.p. injections of TAM resulted in tumor growth inhibition with shrinkage of tumors. The flow...

1H DNP at 1.4 T of Water Doped with a Triarylmethyl-Based Radical

DEFF Research Database (Denmark)

Wind, Robert A.; Ardenkjær-Larsen, Jan Henrik

1999-01-01

Recently a triarylmethyl-based (TAM) radical has been developed for research in biological and other aqueous systems, and in low magnetic fields, 10 mT or less, large 1H dynamic nuclear polarization (DNP) enhancements have been reported. In this paper the DNP properties of this radical have been...... perpendicular to the electric component of the microwave field. It was found that with this probe the temperature increase in the sample after 4 s of microwave irradiation with an incident power of 10 W was only 16°C. For the investigations, 10 mM of the TAM radical was dissolved in deionized, but not degassed...... than the largest high-resolution magnet available to date. It is concluded that DNP MRM in this field, which corresponds to a standard microwave frequency of 9 GHz, has the potential to significantly increase the sensitivity in NMR and MRI experiments of small aqueous samples doped with the TAM radical....

Temporally-controlled site-specific recombination in zebrafish.

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Stefan Hans

Full Text Available Conventional use of the site-specific recombinase Cre is a powerful technology in mouse, but almost absent in other vertebrate model organisms. In zebrafish, Cre-mediated recombination efficiency was previously very low. Here we show that using transposon-mediated transgenesis, Cre is in fact highly efficient in this organism. Furthermore, temporal control of recombination can be achieved by using the ligand-inducible CreER(T2. Site-specific recombination only occurs upon administration of the drug tamoxifen (TAM or its active metabolite, 4-hydroxy-tamoxifen (4-OHT. Cre-mediated recombination is detectable already 4 or 2 hours after administration of TAM or 4-OHT, demonstrating fast recombination kinetics. In addition, low doses of TAM allow mosaic labeling of single cells. Combined, our results show that conditional Cre/lox will be a valuable tool for both, embryonic and adult zebrafish studies. Furthermore, single copy insertion transgenesis of Cre/lox constructs suggest a strategy suitable also for other organisms.

Cross-national comparisons of college students' attitudes toward diet/fitness apps on smartphones.

Science.gov (United States)

Cho, Jaehee; Lee, H Erin; Quinlan, Margaret

2017-10-01

Based on the technology acceptance model (TAM), we explored the nationally-bounded roles of four predictors (subjective norms, entertainment, recordability, and networkability) in determining the TAM variables of perceived usefulness (PU), perceived ease of use (PEOU), and behavioral intention (BI) to use diet/fitness apps on smartphones. College students in the US and South Korea were invited to participate in a survey. We obtained 508 questionnaires (304 from the US and 204 from Korea). Data were analyzed mainly through path analysis. The four factors positively predicted the PU and PEOU of diet/fitness apps. While the effects of the predictors on the three TAM components were generally stronger among the US students than Korean students, the effect of subjective norms on the BI of diet/fitness apps was weaker among Korean students. Findings from the cross-national comparisons were helpful for thoroughly understanding the contextualized mechanisms involved in the adoption of diet/fitness apps.

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

Science.gov (United States)

Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

2016-04-01

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

Long-term outcomes of ductal carcinoma in situ of the breast: a systematic review, meta-analysis and meta-regression analysis

International Nuclear Information System (INIS)

Stuart, Kirsty E.; Houssami, Nehmat; Taylor, Richard; Hayen, Andrew; Boyages, John

2015-01-01

To summarize data on long-term ipsilateral local recurrence (LR) and breast cancer death rate (BCDR) for patients with ductal carcinoma in situ (DCIS) who received different treatments. Systematic review and study-level meta-analysis of prospective (n = 5) and retrospective (n = 21) studies of patients with pure DCIS and with median or mean follow-up time of ≥10 years. Meta-regression was performed to assess and adjust for effects of potential confounders – the average age of women, period of initial treatment, and of bias – follow-up duration on recurrence- and death-rates in each treatment group. LR and BCDR rates by local treatment used were reported. Outside of randomized trials, remaining studies were likely to have tailored patient treatment according to the clinical situation. Nine thousand four hundred and four DCIS cases in 9391 patients with 10-year follow-up were included. The adjusted meta-regression LR rate for mastectomy was 2.6 % (95 % CI, 0.8–4.5); breast-conserving surgery with radiotherapy (RT), 13.6 % (95 % CI, 9.8–17.4); breast-conserving surgery without RT, 25.5 % (95 % CI, 18.1–32.9); and biopsy-only (residual predominately low-grade DCIS following inadequate excision), 27.8 % (95 % CI, 8.4–47.1). RT + tamoxifen (TAM) in conservation surgery (CS) patients resulted in lower LR compared to one or no adjuvant treatments: LR rate for CS + RT + TAM, 9.7 %; CS + RT(no TAM), 14.1 %; CS + TAM(no RT), 24.7 %; CS(alone), 25.1 % (linear trend for treatment P < 0.0001). Compared to CS + RT + TAM, a significantly higher invasive LR was observed for CS(alone), odds ratio (OR) 2.61 (P < 0.0001); CS + TAM(no RT), OR 2.52 (P = 0.001); CS + RT(no TAM), OR 1.59 (P = 0.022). BCDR was similar for mastectomy, breast-conserving surgery with or without RT (1.3–2.0 %) and non-significantly higher for biopsy-only (2.7 %). Additionally, the 15-year follow-up was reported where all like-studies had ≥ 15-year data sets; the biopsy-only patients had a

Revising TAM for hedonic location-based social networks: the influence of TAM, perceived enjoyment, innovativeness and extraversion

NARCIS (Netherlands)

Bouwman, Mariëlle E.; Kommers, Petrus A.M.; van Deursen, Alexander Johannes Aloysius Maria

2014-01-01

As a hedonic information system, a location-based social network (LBSN) is often seen as a promising innovative mobile service. However, research on LBSNs is still limited. Little is known about the factors influencing the intention to use LBSNs. Our study aims to explain the critical factors

Control of Flow Structure and Ignition of Hydrocarbon Fuel in Cavity and Behind Wallstep of Supersonic Duct by Filamentary DC Discharge

Science.gov (United States)

2011-01-01

Lindstrom , K.R. Jackson, S. Williams, R. Givens, W.F. Bailey, C.J. Tam, W.F. Terry, AIAA Journal 47, 2368 (2009). 13. S.T. Sanders, J.A. Baldwin, T.P...A. Kuthi, C. Jiang, P. Ronney, and Martin A. Gundersen, ―Transient Plasma Ignition of Quiescent and Flowing Air/Fuel Mixtures‖ IEEE Transactions on...applications at elevated temperature. JQSRT 103 (2007) 565–577. 17. C.D. Lindstrom , K.R. Jackson, S. Williams, R. Givens, W.F. Bailey, C.J. Tam, W.F

Análisis de la percepción de docentes, usuarios de una plataforma educativa a través de los modelos TPACK, SAMR y TAM3 en una institución de educación superior

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Víctor Manuel Samperio Pacheco

2018-03-01

Full Text Available Este documento da a conocer los resultados de una investigación en la que analizamos la percepción del beneficio educativo de los docentes usuarios del sistema de gestión del aprendizaje (LMS Blackboard, utilizado en la Universidad Autónoma del Estado de Hidalgo (UAEH. El eje central del estudio fue la pregunta ¿cuál es el beneficio de utilizar un LMS como herramienta tecnológica en el proceso educativo de la UAEH? El análisis se basó en las dimensiones teóricas de los modelos TPACK de Mishra y Koehler (2006, el modelo SAMR, desarrollado por Puentedura (2006, y el TAM3, de Venkatesh y Bala (2008. Es un estudio de caso múltiple en el cual usamos varios casos a la vez para abordar y describir una realidad. En esta investigación participaron tres docentes del campus Tlahuelilpan de la UAEH, quienes recurrieron a una entrevista semiestructurada para la obtención de datos. Los resultados muestran la necesidad de una capacitación no solo en lo tecnológico, sino también en lo pedagógico y curricular; una adecuada infraestructura y la modificación en las políticas institucionales. Esto responde a los modelos teóricos mencionados. Es conveniente que las instituciones de educación superior (IES tomen en cuenta lo anterior en el momento de implementar un sistema de gestión del aprendizaje como apoyo en el proceso educativo.

The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer

International Nuclear Information System (INIS)

Loh, Yan Ni; Hedditch, Ellen L; Baker, Laura A; Jary, Eve; Ward, Robyn L; Ford, Caroline E

2013-01-01

Acquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically. An in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. TamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT. These data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

Energy Technology Data Exchange (ETDEWEB)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)

2012-04-06

Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

International Nuclear Information System (INIS)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan

2012-01-01

Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

Assessment of complications in a randomized controlled study on multimodality therapy for patients following breast-conserving surgery

International Nuclear Information System (INIS)

Hiraoka, Masahiro; Inoue, Toshihiko; Kodama, Hiroshi; Sako, Masao

2002-01-01

We conducted a randomized controlled study to evaluate the safety and usefulness of a combined treatment of radiotherapy and chemotherapy with doxifluridine (5'-DFUR) plus tamoxifen (TAM) as an adjuvant therapy for breast cancer patients after conservative surgery. The complications observed in this trial are reported herein. A total of 550 patients were registered and randomized (based on factors such as T, N, with/without radiotherapy) to groups A and B. Drug regimens were: group A, 5'-DFUR 600 mg/body/day for 6 months and TAM 20 mg/body/day for 2 years; group B, 5'-DFUR 600 mg/body/day for 2 years and TAM 20 mg/body/day for 2 years. Radiotherapy (2 Gy x 5 times/week, for 5 weeks) was administered to 88.6% of evaluable patients (481/543). Radiation-related acute adverse reactions occurred in 28.5% of the 481 patients and moderate to severe reactions occurred in 1.5% of the patients. Delayed radiation-related adverse reactions occurred in 17.9% of group A patients and 25.6% of group B patients. Grade 3 reactions occurred in 6 of the group A patients (2.4%) and in 5 of the group B patients (1.9%); all adverse reactions subsided after dose reduction or discontinuation. These findings suggest that the combination therapy of irradiation and 5'-DFUR with TAM is safe for patients after breast conserving surgery. (author)

Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer.

Science.gov (United States)

Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie

2018-05-15

Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

Science.gov (United States)

Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

2011-01-01

Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

Directory of Open Access Journals (Sweden)

Marc Baay

2011-01-01

Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

Technology Acceptance and User Experience: A Review of the Experiential Component in HCI

DEFF Research Database (Denmark)

Hornbæk, Kasper; Hertzum, Morten

2017-01-01

Understanding the mechanisms that shape the adoption and use of information technology is central to human-computer interaction. Two accounts are particularly vocal about these mechanisms, namely the technology acceptance model (TAM) and work on user experience (UX) models. In this study we review...... 37 papers in the overlap between TAM and UX models to explore the experiential component of human-computer interactions. The models provide rich insights about what constructs influence the experiential component of human-computer interactions and about how these constructs are related. For example...

Hierarchical Self Assembly of Patterns from the Robinson Tilings: DNA Tile Design in an Enhanced Tile Assembly Model.

Science.gov (United States)

Padilla, Jennifer E; Liu, Wenyan; Seeman, Nadrian C

2012-06-01

We introduce a hierarchical self assembly algorithm that produces the quasiperiodic patterns found in the Robinson tilings and suggest a practical implementation of this algorithm using DNA origami tiles. We modify the abstract Tile Assembly Model, (aTAM), to include active signaling and glue activation in response to signals to coordinate the hierarchical assembly of Robinson patterns of arbitrary size from a small set of tiles according to the tile substitution algorithm that generates them. Enabling coordinated hierarchical assembly in the aTAM makes possible the efficient encoding of the recursive process of tile substitution.

Changes in the transcriptome of the human endometrial Ishikawa cancer cell line induced by estrogen, progesterone, tamoxifen, and mifepristone (RU486 as detected by RNA-sequencing.

Directory of Open Access Journals (Sweden)

Karin Tamm-Rosenstein

Full Text Available BACKGROUND: Estrogen (E2 and progesterone (P4 are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM and mifepristone (RU486 are widely used in breast cancer therapy and for contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1 showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage.

Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

Science.gov (United States)

Gavazza, Sergio

Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

Kelios pastabos apie baltų parodomųjų įvardžių vietininko formas

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Albertas Rosinas

2011-05-01

Full Text Available ZUM LOKATIVUS SINGULARIS DER DEMONSTRATIVPRONOMINA DER BALTISCHEN SPRACHENZusammenfassungVorliegender Beitrag setzt sich das Ziel, die Bildung und Entwicklung des Inessivus und Adessivus Sg. M. der Demonstrativpronomina der baltischen Sprachen zu erklären.1. Auf Grund des Inessivus Sg. M. liegt, des Verfassers Meinung nach, der alte Lokativus * tami, dessen Endung -i im Litauischen durch die neue *ḗn ersetzt ist. Aus der Form *tami + ēn konnte nur lett. tamī und lit. *tamije, vgl. iamije BrP, entstehen.2. Das Ersetzen des Femininums toj durch Maskulinum tam(i in den südniederlitauischen Mundarten wurde infolge des Zusammenfallens der Lokativendungen von Substantiva der io, iā, ē, i und konsonantischen Stämme bedingt.3. Im Lettischen vorhandene Lokativus tamā bekam ihre Endung -ā aus der Nebenform tā und demgemäss tamie — aus dem substantivischen Lokativus der i- Stämme, der auf -ie auslautet. Die Formen tanā und tanī scheinen das Ergebnis einer Vermischung von Lokativus tamā und Illativus tan (demgemäss Lokativus tamī und Illativus tan su sein.4. Adessivus Sg. M., der in den altlitauischen Schriften und in den isolierten litauischen Mundarten gebraucht wird, wurde vom alten Lokativus und einer Postposition -pi<-pie gebildet:a tamip und tamimp — diese kommen nur in altlitauischen Schriften vor. Die zweite Form (tamimp hat ihre Endung -mp von támp, b die Form támp scheint eine Neubildung zu sein; aus der Silbe –mi- (tami-pi fiel -i- aus, um dadurch die Anzahl der Silben im Deklinationssystem auszu­gleichen, c die Form túmp in K. Sirwids Punktay bekam ihr unregelmässiges -um- nach dem Mus­ter Allativus Pluralis durch Vermittlung der Substantiva der u- Stämme. Derselben Herkunft ist wahr­scheinlich auch die in Gervėčiai gebräuchliche Form túnk, anstatt *támk.

Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition

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Cristiana Perrotta

2018-05-01

Full Text Available Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO-generating enzyme inducible nitric oxide synthase (iNOS. NO has divergent effects on tumors, since it can either stimulate tumor cells growth or promote their death depending on the source of it; likewise the role of iNOS in cancer differs depending on the cell type. The role of NO generated by TAMs has not been investigated. Using different tumor models in vitro and in vivo we found that NO generated by iNOS of M2-polarized TAMs is able to protect tumor cells from apoptosis induced by the chemotherapeutic agent cisplatin (CDDP. Here, we demonstrate that the protective effect of NO depends on the inhibition of acid sphingomyelinase (A-SMase, which is activated by CDDP in a pathway involving the death receptor CD95. Mechanistic insights indicate that NO actions occur via generation of cyclic GMP and activation of protein kinase G (PKG, inducing phosphorylation of syntaxin 4 (synt4, a SNARE protein responsible for A-SMase trafficking and activation. Noteworthy, phosphorylation of synt4 at serine 78 by PKG is responsible for the proteasome-dependent degradation of synt4, which limits the CDDP-induced exposure of A-SMase to the plasma membrane of tumor cells. This inhibits the cytotoxic mechanism of CDDP reducing A-SMase-triggered apoptosis. This is the first demonstration that endogenous NO system is a key mechanism through which TAMs protect tumor cells from chemotherapeutic drug-induced apoptosis. The identification of the pathway responsible for A-SMase activity downregulation in tumors leading to chemoresistance warrants further investigations as a means to identify new anti-cancer molecules capable of specifically

Trophic transfer of trace metals: Subcellular compartmentalization in a polychaete and assimilation by a decapod crustacean

Science.gov (United States)

Rainbow, P.S.; Poirier, L.; Smith, B.D.; Brix, K.V.; Luoma, S.N.

2006-01-01

The chemical form of accumulated trace metal in prey is important in controlling the bioavailataility of dietary metal to a predator. This study investigated the trophic transfer of radiolabelled Ag, Cd and Zn from the polychaete worm Nereis diversicolor to the decapod crustacean Palaemonetes varians. We used 2 populations of worms with different proportions of accumulated metals in different subcellular fractions as prey, and loaded the worms with radiolabelled metals either from sediment or from solution. Accumulated radiolabelled metals were fractionated into 5 components : metal-rich granules (MRG), cellular debris, organelles, metallothionein-like proteins (MTLP), and other (heat-sensitive) proteins (HSP). Assimilation efficiencies (AE) of the metals by P. varians were measured from the 4 categories of prey (i.e. 2 populations, radiolabelled from sediment or solution). There were significant differences for each metal between the AEs from the different prey categories, confirming that origin of prey and route of uptake of accumulated trace metal will cause intraspecific differences in subsequent metal assimilation. Correlations were sought between AEs and selected fractions or combinations of fractions of metals in the prey-MRG, Trophically Available Metal (TAM = MTLP + HSP + organelles) and total protein (MTLP + HSP). TAM explained 28% of the variance in AEs for Ag, but no consistent relationships emerged between AEs and TAM or total protein when the metals were considered separately. AEs did, however, show significant positive regressions with both TAM and total protein when the 3 metals were considered together, explaining only about 21 % of the variance in each case. A significant negative relationship was observed between MRG and AE for all metals combined. The predator (P. varians) can assimilate dietary metal from a range of the fractions binding metals in the prey (N. diversicolor), with different assimilation efficiencies summated across these

Does Usability Matter? An Analysis of the Impact of Usability on Technology Acceptance in ERP Settings

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Brenda M Scholtz

2016-11-01

Full Text Available Though the field of management information systems, as a sector and a discipline, is the inventor of many guidelines and models, it appears to be a slow runner on practical implications of interface usability. This usability can influence end users’ attitude and behavior to use IT. The purpose of this paper was to examine the interface usability of a popular Enterprise Resource Planning (ERP software system, SAP, and to identify related issues and implications to the Technology Acceptance Model (TAM. A survey was conducted of 112 SAP ERP users from an organization in the heavy metal industry in Bangladesh. The partial least squares technique was used to analyze the survey data. The survey findings empirically confirmed that interface usability has a significant impact on users’ perceptions of usefulness and ease of use which ultimately affects attitudes and intention to use the ERP software. The research model extends the TAM by incorporating three criteria of interface usability. It is the first known study to investigate usability criteria as an extension of TAM.

Discussions about acceptance of the free software for management and creation of referencial database for papers

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Flavio Ribeiro Córdula

2016-03-01

Full Text Available Objective. This research aimed to determine the degree of acceptance, by the use of the Technology Acceptance Model - TAM, of the developed software, which allows the construction and database management of scientific articles aimed at assisting in the dissemination and retrieval of stored scientific production in digital media. Method. The research is characterized as quantitative, since the TAM, which guided this study is essentially quantitative. A questionnaire developed according to TAM guidelines was used as a tool for data collection. Results. It was possible to verify that this software, despite the need of fixes and improvements inherent to this type of tool, obtained a relevant degree of acceptance by the sample studied. Conciderations. It also should be noted that although this research has been directed to scholars in the field of information science, the idea that justified the creation of the software used in this study might contribute to the development of science in any field of knowledge, aiming at the optimization results of a search conducted in a specialized database can provide.

Effect of paclitaxel, epirubicin and tamoxifen on labelling index in cultured ehrlich ascites tumor cells

International Nuclear Information System (INIS)

Arican, G. Oe.; Oezalpan, A.

2001-01-01

The effect of Paclitaxel (PAC), Epirubicin (EPR) and Tamoxifen (TAM) on ''3H-thymidine labelling index (''3H-TdR LI) of Ehrlich ascites tumor cells (EAT) was investigated in cultured. In the present study, an estrogen receptor positive ER(+) hyper diploid cell lines were studied. We used optimum doses of PAC, EPR and TAM (12 mg/ml, 12 mg/ml and 2 mg/ml, respectively). Cells were treated with these doses for 0, 4, 8, 16 and 32 hours. At the end of these periods, both control and treated cells were labelled for 5 mCi/ml 3H-thymidine for 30 minutes. The results showed that inhibition of DNA synthesis in cultured EAT cells were increased in the combined treatment of two drugs when compared to the treatment of a single drug (p<0.01). In the treatment of three drugs, however, this effect reached a maximum (p<0.001). As a result, PAC+EPR+TAM treatment's had a maximum synergistic effect at 4 hours treatment

Studies on the feasibility of using crystalline silicotitanates for the separation of cesium-137 from fast reactor high-level liquid waste

International Nuclear Information System (INIS)

Venkatesan, K.A.; Sukumaran, V.; Antony, M.P.; Srinivasan, T.G.

2009-01-01

The commercially available crystalline silicotitanate inorganic ion xchanger, IONSIV IE-911, and its parent precursor, TAM-5, have been valuated for the removal of 137 Cs from nitric acid medium and simulated high-level liquid waste. The distribution coefficient (K d ) of cesium ecreased with increasing nitric acid concentration and at 3.0 M nitric acid, distribution coefficient of 1150 mL/g and 2600 mL/g were obtained for ONSIV IE-911 and TAM-5, respectively. Rapid uptake of cesium followed by the establishment of equilibrium occurring within three hours. Loading of cesium n ion exchangers increased with the increase in the concentration of cesium n aqueous phase and from Langmuir adsorption model the apparent capacity of cesium was 69 mg/g and 82 mg/g for IONSIV IE-911 and TAM-5, respectively. The performance of the sorbent under dynamic conditions was assessed by following breakthrough (BT) curve up to C/C o = 1, where C and C o are the concentrations of cesium in the effluent and feed, respectively. (author)

Examining Information Technology Acceptance by Individual Professionals

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Licen Indahwati Darsono

2005-06-01

Full Text Available The mixed results of information technology (IT investment have made the investigation of user acceptance of IT increasingly challenging. A growing body of research in user acceptance of IT literature has limited focus on individual professionals as target users. Therefore, this research investigates how external variables, namely individual differences and system characteristics influence lecturers as individual professionals to accept the internet technology. Technology Acceptance Model (TAM and Theory of Planned Behavior (TPB are used as the main reference in this research. Findings of this research indicate that individual differences (computer self-efficacy, knowledge of search domain and system characteristics (terminology, screen design, relevance have indirect impact through perceived ease of use, perceived usefulness, and attitude on lecturers’ intention to use the internet. Specifically, computer self-efficacy and screen design have direct and indirect impact on intention. One issue concerning with the explanatory power of the proposed research model, which is based on TAM and TPB, compared to the rival model, which is called extended TAM, is also analyzed.

An extension of technology acceptance model to determine factors that influence the intention to use electronic collection system in Nigerian federal hospitals

Science.gov (United States)

Kabir, Muhammad Auwal; Saidin, Siti Zabedah; Ahmi, Aidi

2017-10-01

The aim of this paper is to develop a conceptual framework that would be used in determining the factors that influence the behavioral intention to use electronic collection system in federal government owned hospitals in Nigeria. The framework is supported by Technology Acceptance Model (TAM) as the underlying theory of the study. Past literature on individual user intention were thoroughly reviewed and found that TAM is fit appropriate in explaining the phenomenon under study. Based on the reviewed literature, it is expected that perceived usefulness and perceived ease of use will influence the intention of users (employees) to use e-collection system in the performance of their job tasks in Nigerian federal hospitals. In other words, users with higher perception on the system's usefulness and its ease of use are more likely to express their interest and willingness to use the system. In addition, the study has extended TAM with facilitating conditions construct and the research is expected to discover the level of its influence on behavioral intention to use e-collection system.

Evaluation of teledermatology adoption by health-care professionals using a modified Technology Acceptance Model.

Science.gov (United States)

Orruño, Estibalitz; Gagnon, Marie Pierre; Asua, José; Ben Abdeljelil, Anis

2011-01-01

We examined the main factors affecting the intention of physicians to use teledermatology using a modified Technology Acceptance Model (TAM). The investigation was carried out during a teledermatology pilot study conducted in Spain. A total of 276 questionnaires were sent to physicians by email and 171 responded (62%). Cronbach's alpha was acceptably high for all constructs. Theoretical variables were well correlated with each other and with the dependent variable (Intention to Use). Logistic regression indicated that the original TAM model was good at predicting physicians' intention to use teledermatology and that the variables Perceived Usefulness and Perceived Ease of Use were both significant (odds ratios of 8.4 and 7.4, respectively). When other theoretical variables were added, the model was still significant and it also became more powerful. However, the only significant predictor in the modified model was Facilitators with an odds ratio of 9.9. Thus the TAM was good at predicting physicians' intention to use teledermatology. However, the most important variable was the perception of Facilitators to using the technology (e.g. infrastructure, training and support).

Determinantes de guerra de preços e conluio no transporte aéreo brasileiro

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Ana Carolina Campana Nascimento

2011-12-01

Full Text Available Este artigo tem como objetivo identificar possíveis padrões de guerras de preço e formação de conluio pelas companhias aéreas que operam no trecho Rio de Janeiro - São Paulo (GOL e TAM e estimar as condições que facilitaram os dois fenômenos no período de 2002 a 2010. Para tanto, utilizaram-se a teoria dos jogos, a teoria econômica dos cartéis e os modelos logit como instrumentos de análise. Os resultados obtidos mostram que os fatores determinantes desses dois fenômenos são diferentes para cada companhia aérea: a TAM apresentou maior probabilidade de formação de conluio que a GOL no período analisado, enquanto esta última teve maior probabilidade de entrar em uma guerra de preços do que em um conluio. Além disso, as variáveis utilizadas neste estudo não conseguiram explicar a probabilidade da TAM praticar guerra de preços.

Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-gamma production by tumor-associated macrophages.

Science.gov (United States)

Komohara, Yoshihiro; Takemura, Kenichi; Lei, Xiao Feng; Sakashita, Naomi; Harada, Mamoru; Suzuki, Hiroshi; Kodama, Tatsuhiko; Takeya, Motohiro

2009-11-01

Class A scavenger receptors (SR-A, CD204) are highly expressed in tumor-associated macrophages (TAM). To investigate the function of SR-A in TAM, wild-type and SR-A-deficient (SR-A(-/-)) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR-A(-/-) mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)-gamma mRNA increased significantly in tumor tissues from SR-A(-/-) mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN-gamma production by cultured macrophages, and production of NO and IFN-gamma increased in SR-A(-/-) macrophages in vitro. IFN-beta production by cultured macrophages was also elevated in SR-A(-/-) macrophages in vitro. These results suggested that the antitumor activity of macrophages increased in SR-A(-/-) mice because of upregulation of NO and IFN-gamma production. These data indicate an important role of SR-A in regulating TAM function by inhibiting toll-like receptor (TLR)4-IFN-beta signaling.

Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

International Nuclear Information System (INIS)

Clarke, C.L.; Satyaswaroop, P.G.

1985-01-01

A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with [17 alpha-methyl- 3 H]promegestone ([ 3 H]R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of [3H]R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of [ 3 H]R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases*

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Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J.; Nie, Guangjun

2016-01-01

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID:26895960

G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer

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Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J.; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

2016-01-01

ABSTRACT Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DRlo macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p CSF blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called “gate-keeper” subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression. PMID:27141367

Ethanol Extract of Mylabris phalerata Inhibits M2 Polarization Induced by Recombinant IL-4 and IL-13 in Murine Macrophages

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Hwan-Suck Chung

2017-01-01

Full Text Available Mylabris phalerata (MP is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment. In this line, we screened oriental medicines to find M1 polarizing medicines in M2-polarized macrophages. Among approximately 400 types of oriental medicine, the ethanol extract of M. phalerata (EMP was the most proficient in increasing TNF-α secretion in M2-polarized macrophages and TAM. Although EMP enhanced the levels of an M1 cytokine (TNF-α and a marker (CD86, it significantly reduced the levels of an M2 marker (arginase-1 in M2-polarized macrophages. In addition, EMP-treated macrophages increased the levels of M1 markers (Inos and Tnf-α and reduced those of the enhanced M2 markers (Fizz-1, Ym-1, and arginase-1. EMP-treated macrophages significantly reduced Lewis lung carcinoma cell migration in a transwell migration assay and inhibited EL4-luc2 lymphoma proliferation. In our mechanism study, EMP was found to inhibit STAT3 phosphorylation in M2-polarized macrophages. These results suggest that EMP is effective in treating TAM-mediated tumor progression and metastasis.

Therapeutic effects of anti-CD115 monoclonal antibody in mouse cancer models through dual inhibition of tumor-associated macrophages and osteoclasts.

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Laetitia Fend

Full Text Available Tumor progression is promoted by Tumor-Associated Macrophages (TAMs and metastasis-induced bone destruction by osteoclasts. Both myeloid cell types depend on the CD115-CSF-1 pathway for their differentiation and function. We used 3 different mouse cancer models to study the effects of targeting cancer host myeloid cells with a monoclonal antibody (mAb capable of blocking CSF-1 binding to murine CD115. In mice bearing sub-cutaneous EL4 tumors, which are CD115-negative, the anti-CD115 mAb depleted F4/80(+ CD163(+ M2-type TAMs and reduced tumor growth, resulting in prolonged survival. In the MMTV-PyMT mouse model, the spontaneous appearance of palpable mammary tumors was delayed when the anti-CD115 mAb was administered before malignant transition and tumors became palpable only after termination of the immunotherapy. When administered to mice already bearing established PyMT tumors, anti-CD115 treatment prolonged their survival and potentiated the effect of chemotherapy with Paclitaxel. As shown by immunohistochemistry, this therapeutic effect correlated with the depletion of F4/80(+CD163(+ M2-polarized TAMs. In a breast cancer model of bone metastasis, the anti-CD115 mAb potently blocked the differentiation of osteoclasts and their bone destruction activity. This resulted in the inhibition of cancer-induced weight loss. CD115 thus represents a promising target for cancer immunotherapy, since a specific blocking antibody may not only inhibit the growth of a primary tumor through TAM depletion, but also metastasis-induced bone destruction through osteoclast inhibition.

Improving social marketing mix in non-profit organizations

OpenAIRE

Bilvinaitė, Arūnė

2014-01-01

Socialinio marketingo sąvoka dažniausiai yra siejama su ne pelno siekiančiomis organizacijomis. Marketingo principai tradiciškai naudojami pateikiant prekes ar paslaugas vartotojams. Tačiau pastaruoju metu jie vis dažniau taikomi, siekiant pagelbėti žmonėms ir aplinkai, veikti tiek atskirų asmenų ar jų grupių bei visos visuomenės elgseną dėl tam tikrų priežasčių, siekiant tam tikro rezultato. Toks marketingo naudojimas sąlygojo socialinio marketingo koncepcijos atsiradimą. Darbo objektas- soc...

Panda crosses the Atlantic

International Nuclear Information System (INIS)

Anon.

1999-01-01

The development of the Panda software by Electricite de France (EdF) for monitoring hydroelectric power plants is traced from the early stages using TAM-TAM software for the Macintosh for data acquisition, checking, transfer to external sites, and archiving, to the development of Panda software in order to make the software compatible with remote measurement systems. The installation of Panda at two Argentinian hydroelectric power stations by EdF to make the monitoring of systems more reliable is reported, and the different chain of operations carried out by Panda are described. Panda's technical data, and simple data collection systems are outlined. (UK)

The 'TaR(T)AM' (and 'CUHN') trick

International Nuclear Information System (INIS)

Poizat, Francois

2009-01-01

The author criticizes the TarTAM (transient regulated tariff of market adjustment) which was introduced in 2006 to circumvent the European directive of electricity market deregulation, and to support some industrial clients. The author gives a summarized description of this arrangement, discusses the cost of its implementation and the creation of the CUHN (hydraulic and nuclear unitary contribution). He comments the reaction of the CRE (Commission for energy regulation), the changes in the contribution and distribution of these arrangements. The law articles which introduced the TarTAM are given in appendix, and the main and critical aspects are outlined

Biorremediación de los efluentes de cultivo del camarón Litopenaeus vannamei (Boone, 1931 utilizando tapetes microbianos en un sistema de recirculación Bioremediacion of effluents ones of the culture of Litopenaeus vannamei (Boone, 1931 using microbial mats in a recirculating system

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Carlos Lezama-Cervantes

2010-01-01

Full Text Available Se desarrolló un sistema de recirculación (SR integrando el cultivo del camarón con tapetes microbianos buscando mitigar los impactos ambientales de los subproductos del cultivo del camarón y avanzar hacia la biorremediación del agua de cultivo. Los consorcios microbianos obtenidos de ambientes naturales (TaM estuvieron constituidos por bacterias (55,6%, cianófitas (18,4%, diatomeas (9%, nemátodos (5,6% y clorófitas (1,4%, entre los grupos taxonómicos principales. La remoción de nutrientes y sólidos se evaluó en un SR (2 ciclos/hora conteniendo (n = 3 60 y 120 ind m-2 de Litopenaeus vannamei. Los resultados demostraron que los TaM redujeron los niveles de nitrógeno amoniacal por encima del 71% diariamente; la demanda bioquímica de oxígeno (DBO5 se redujo más de 68% y los sólidos suspendidos (SST hasta en 62% al compararse con los sistemas control (p 0,05. El agua bio-remediada tiene un efecto positivo en el cultivo de Litopenaeus vannamei, y promueve el crecimiento y sobrevivencia en presencia de TaM en el SR.We developed a recirculating system integrating shrimp culture with microbial mats aiming to mitigate the environmental impacts of by-products from shrimp culture and to advance toward the bioremediation of the shrimp culture water. The microbial consortia collected from natural environments (TaM was constituted by bacteria (55.6%, Cyanophyte (18.4%, diatoms (9%, nematods (5.6% and Chlorophyte algae (1.4% among the major taxonomic groups. The removal of nutrients and solids by these mats was assessed in a recirculating system (2 cycles/hour (n = 3 containing 60 and 120 ind m-2 of Litopenaeus vannamei. Results showed that the microbial mat reduces daily up to 71% of ammonia nitrogen, decreases around 68% of the biochemical oxygen demand (DBO5 and up to 62% of suspended solids (SST when comparing to the control systems (p 0.05. The Bioremediated culture water had a positive effect on the culture of Litopenaeus vannamei, and

Crustal structure of the Transantarctic Mountains, Ellsworth Mountains and Marie Byrd Land, Antarctica: constraints on shear wave velocities, Poisson's ratios and Moho depths

Science.gov (United States)

Ramirez, C.; Nyblade, A.; Emry, E. L.; Julià, J.; Sun, X.; Anandakrishnan, S.; Wiens, D. A.; Aster, R. C.; Huerta, A. D.; Winberry, P.; Wilson, T.

2017-12-01

A uniform set of crustal parameters for seismic stations deployed on rock in West Antarctica and the Transantarctic Mountains (TAM) has been obtained to help elucidate similarities and differences in crustal structure within and between several tectonic blocks that make up these regions. P-wave receiver functions have been analysed using the H-κ stacking method to develop estimates of thickness and bulk Poisson's ratio for the crust, and jointly inverted with surface wave dispersion measurements to obtain depth-dependent shear wave velocity models for the crust and uppermost mantle. The results from 33 stations are reported, including three stations for which no previous results were available. The average crustal thickness is 30 ± 5 km along the TAM front, and 38 ± 2 km in the interior of the mountain range. The average Poisson's ratios for these two regions are 0.25 ± 0.03 and 0.26 ± 0.02, respectively, and they have similar average crustal Vs of 3.7 ± 0.1 km s-1. At multiple stations within the TAM, we observe evidence for mafic layering within or at the base of the crust, which may have resulted from the Ferrar magmatic event. The Ellsworth Mountains have an average crustal thickness of 37 ± 2 km, a Poisson's ratio of 0.27, and average crustal Vs of 3.7 ± 0.1 km s-1, similar to the TAM. This similarity is consistent with interpretations of the Ellsworth Mountains as a tectonically rotated TAM block. The Ross Island region has an average Moho depth of 25 ± 1 km, an average crustal Vs of 3.6 ± 0.1 km s-1 and Poisson's ratio of 0.30, consistent with the mafic Cenozoic volcanism found there and its proximity to the Terror Rift. Marie Byrd Land has an average crustal thickness of 30 ± 2 km, Poisson's ratio of 0.25 ± 0.04 and crustal Vs of 3.7 ± 0.1 km s-1. One station (SILY) in Marie Byrd Land is near an area of recent volcanism and deep (25-40 km) seismicity, and has a high Poisson's ratio, consistent with the presence of partial melt in the crust.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

Science.gov (United States)

Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

2014-01-01

Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving

Depletion of tumor-associated macrophages switches the epigenetic profile of pancreatic cancer infiltrating T cells and restores their anti-tumor phenotype.

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Borgoni, Simone; Iannello, Andrea; Cutrupi, Santina; Allavena, Paola; D'Incalci, Maurizio; Novelli, Francesco; Cappello, Paola

2018-01-01

Pancreatic Ductal Adenocarcinoma (PDA) is characterized by a complex tumor microenvironment that supports its progression, aggressiveness and resistance to therapies. The delicate interplay between cancer and immune cells creates the conditions for PDA development, particularly due to the functional suppression of T cell anti-tumor effector activity. However, some of the mechanisms involved in this process are still poorly understood. In this study, we analyze whether the functional and epigenetic profile of T cells that infiltrate PDA is modulated by the microenvironment, and in particular by tumor-associated macrophages (TAMs). CD4 and CD8 T cells obtained from mice orthotopically injected with syngeneic PDA cells, and untreated or treated with Trabectedin, a cytotoxic drug that specifically targets TAMs, were sorted and analyzed by flow cytometry and characterized for their epigenetic profile. Assessment of cytokine production and the epigenetic profile of genes coding for IL10, T-bet and PD1 revealed that T cells that infiltrated PDA displayed activated Il10 promoter and repressed T-bet activity, in agreement with their regulatory phenotype (IL10 high /IFNγ low , PD1 high ). By contrast, in Trabectedin-treated mice, PDA-infiltrating T cells displayed repressed Il10 and Pdcd1 and activated T-bet promoter activity, in accordance with their anti-tumor effector phenotype (IL10 low /IFNγ high ), indicating a key role of TAMs in orchestrating functions of PDA-infiltrating T cells by modulating their epigenetic profile towards a pro-tumoral phenotype. These results suggest the targeting of TAMs as an efficient strategy to obtain an appropriate T cell anti-tumor immune response and open new potential combinations for PDA treatment.

[The Technology Acceptance Model and Its Application in a Telehealth Program for the Elderly With Chronic Illnesses].

Science.gov (United States)

Chang, Chi-Ping

2015-06-01

Many technology developments hold the potential to improve the quality of life of people and make life easier and more comfortable. New technologies have been well accepted by most people. Information sharing in particular is a major catalyst of change in our current technology-based society. Technology has widely innovated life and drastically changed lifestyles. The Technology Acceptance Model (TAM), a model developed to address the rapid advances in computer technology, is used to explain and predict user acceptance of new information technology. In the past, businesses have used the TAM as an assessment tool to predict user acceptance when introducing new technology products. They have also used external factors in the model to influence user perceptions and beliefs and to ensure the successful spread of new technologies. Informatization plays a critical role in healthcare services. Due to the rapid aging of populations and upward trends in the incidence of chronic illness, requirements for long-term care have increased in both quality and quantity. Therefore, there has been an increased emphasis on integrating healthcare and information technology. However, most elderly are significantly less adept at technology use than the general population. Therefore, we reexamined the effect that the essential concepts in a TAM exerted on technology acceptance. In the present study, the technology acceptance experience with regard to telehealth of the elderly was used as an example to explain how the revised technology acceptance model (TAM 2) may be effectively applied to enhance the understanding of technology care among nurses. The results may serve as a reference for future research on healthcare-technology use in long-term care or in elderly populations.

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases.

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Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J; Nie, Guangjun

2016-04-15

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Acceptance of Health Information Technologies, Acceptance of Mobile Health: A Review Article.

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Garavand, A; Samadbeik, M; Kafashi, M; Abhari, Sh

2017-12-01

Mobile health is one of the new technologies for the utilization of health information. For its successful implementation as well as any other system, we must primarily measure the adoption and use of its factors. The purpose of this study was to systematically investigate published articles about the factors affecting the adoption of mobile health and categorizing the factors affecting the adoption of this system. This study is a comprehensive review done by searching major databases such as Google Scholar, Emerald, Science Direct, Iran Medex, SID, Magiran, Pub med, etc. In addition, we use Mobile, mobile Health + adoption, mobile Health + TAM, Health + TAM keywords in the range of 2004 to 2015. Among the studies that use information technology theories to survey the factors affecting the adoption of mobile health, TAM model was used more than other models. Factors such as perceived ease of use, perceived usefulness and facilitating condition form TUATU are the most effective in the adoption of mobile health. Results showed that by considering factors such as perceived ease of use, perceived usefulness and facilitating condition can increase the adoption of mobile health system. Consequently, these factors are recommended to be considered in planning to run systems.

Crystallization and preliminary X-ray crystallographic studies of β-transaminase from Mesorhizobium sp. strain LUK

International Nuclear Information System (INIS)

Kim, Bokyung; Park, Ok Kyeung; Bae, Ju Young; Jang, Tae-ho; Yoon, Jong Hwan; Do, Kyoung Hun; Kim, Byung-Gee; Yun, Hyungdon; Park, Hyun Ho

2011-01-01

β-Transaminase from Mesorhizobium sp. strain LUK was crystallized. The crystals were found to belong to the orthorhombic space group C222 1 , with unit-cell parameters a = 90.91, b = 192.17, c = 52.75 Å. The crystals were obtained at 293 K and diffracted to a resolution of 2.5 Å. β-Transaminase (β-TA) catalyzes the transamination reaction between β-aminocarboxylic acids and keto acids. This enzyme is a particularly suitable candidate for use as a biocatalyst for the asymmetric synthesis of enantiochemically pure β-amino acids for pharmaceutical purposes. The β-TA from Mesorhizobium sp. strain LUK (β-TAMs) belongs to a novel class in that it shows β-transaminase activity with a broad and unique substrate specificity. In this study, β-TAMs was overexpressed in Escherichia coli with an engineered C-terminal His tag. β-TAMs was then purified to homogeneity and crystallized at 293 K. X-ray diffraction data were collected to a resolution of 2.5 Å from a crystal that belonged to the orthorhombic space group C222 1 , with unit-cell parameters a = 90.91, b = 192.17, c = 52.75 Å

Full-sky formulae for weak lensing power spectra from total angular momentum method

International Nuclear Information System (INIS)

Yamauchi, Daisuke; Taruya, Atsushi; Namikawa, Toshiya

2013-01-01

We systematically derive full-sky formulae for the weak lensing power spectra generated by scalar, vector and tensor perturbations from the total angular momentum (TAM) method. Based on both the geodesic and geodesic deviation equations, we first give the gauge-invariant expressions for the deflection angle and Jacobi map as observables of the CMB lensing and cosmic shear experiments. We then apply the TAM method, originally developed in the theoretical studies of CMB, to a systematic derivation of the angular power spectra. The TAM representation, which characterizes the total angular dependence of the spatial modes projected along a line-of-sight, can carry all the information of the lensing modes generated by scalar, vector, and tensor metric perturbations. This greatly simplifies the calculation, and we present a complete set of the full-sky formulae for angular power spectra in both the E-/B-mode cosmic shear and gradient-/curl-mode lensing potential of deflection angle. Based on the formulae, we give illustrative examples of non-vanishing B-mode cosmic shear and curl-mode of deflection angle in the presence of the vector and tensor perturbations, and explicitly compute the power spectra

Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue based regimens in ART-naïve and experienced patients

DEFF Research Database (Denmark)

Silberstein, F; Cozzi-Lepri, A; Ruiz, L

2007-01-01

BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started ...... were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. CONCLUSIONS: This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART.......BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started TA...... therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements >400 copies/mL after...

Acceptance of health information technology in health professionals: an application of the revised technology acceptance model.

Science.gov (United States)

Ketikidis, Panayiotis; Dimitrovski, Tomislav; Lazuras, Lambros; Bath, Peter A

2012-06-01

The response of health professionals to the use of health information technology (HIT) is an important research topic that can partly explain the success or failure of any HIT application. The present study applied a modified version of the revised technology acceptance model (TAM) to assess the relevant beliefs and acceptance of HIT systems in a sample of health professionals (n = 133). Structured anonymous questionnaires were used and a cross-sectional design was employed. The main outcome measure was the intention to use HIT systems. ANOVA was employed to examine differences in TAM-related variables between nurses and medical doctors, and no significant differences were found. Multiple linear regression analysis was used to assess the predictors of HIT usage intentions. The findings showed that perceived ease of use, but not usefulness, relevance and subjective norms directly predicted HIT usage intentions. The present findings suggest that a modification of the original TAM approach is needed to better understand health professionals' support and endorsement of HIT. Perceived ease of use, relevance of HIT to the medical and nursing professions, as well as social influences, should be tapped by information campaigns aiming to enhance support for HIT in healthcare settings.

Corrosion inhibition properties of pyrazolylindolenine compounds on copper surface in acidic media

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Ebadi Mehdi

2012-12-01

Full Text Available Abstract Background The corrosion inhibition performance of pyrazolylindolenine compounds, namely 4-(3,3-dimethyl-3H-indol-2-yl-pyrazole-1-carbothioamide (InPzTAm, 4-(3,3-dimethyl-3H-indol-2-yl-1H-pyrazole-1-carbothiohydrazide (InPzTH and 3,3-dimethyl-2-(1-phenyl-1H-pyrazol-4-yl-3H-indole (InPzPh, on copper in 1M HCl solution is investigated by electrochemical impedance spectroscopy (EIS, open circuit potential (OCP and linear scan voltammetry (LSV techniques. Results The results show that the corrosion rate of copper is diminished by the compounds with the inhibition strength in the order of: InPzTAm> InPzTH > InPzPh. The corrosion inhibition efficiencies for the three inhibitors are 94.0, 91.4 and 79.3, for InPzTAm, InPzTH and InPzPh respectively with the same inhibitor concentration (2 mM. Conclusion From the EIS, OCP and LSV results it was concluded that pyrazolylindolenine compounds with S-atom (with an amine group have illustrated better corrosion inhibition performance compared to hydrazine and phenyl group.

A trap activation model for hydrogen retention and isotope exchange in some refractory materials

International Nuclear Information System (INIS)

Brice, D.K.; Doyle, B.L.

1982-01-01

Our recently-developed Local Mixing Model (LMM) has been successful in describing and predicting the properties of hydrogen retention and isotope exchange for a variety of refractory materials. For some materials, however, the detailed predictions of the LMM are not observed. A Trap Activation Model (TAM) is proposed here to account for the observed departures from the LMM. Comparison of experimental room temperature saturation depth profiles for H + →Si with the predictions of TAM suggests that the hydrogen traps are multiple-vacancy complexes in this system. The observed profiles result from a beam-induced competition between trap creation/annihilation and H-trapping/detrapping. (orig.)

Applying the Technology Acceptance Model and flow theory to Cyworld user behavior: implication of the Web2.0 user acceptance.

Science.gov (United States)

Shin, Dong-Hee; Kim, Won-Yong; Kim, Won-Young

2008-06-01

This study explores attitudinal and behavioral patterns when using Cyworld by adopting an expanded Technology Acceptance Model (TAM). A model for Cyworld acceptance is used to examine how various factors modified from the TAM influence acceptance and its antecedents. This model is examined through an empirical study involving Cyworld users using structural equation modeling techniques. The model shows reasonably good measurement properties and the constructs are validated. The results not only confirm the model but also reveal general factors applicable to Web2.0. A set of constructs in the model can be the Web2.0-specific factors, playing as enhancing factor to attitudes and intention.

Technology acceptance model and the paths to online customer loyalty in an emerging market

Directory of Open Access Journals (Sweden)

Nguyen Thi Tuyet Mai

2013-12-01

Full Text Available The technology acceptance model (TAM has been well-known for decades. However, the global adoption of the Internet creates new interests in utilizing TAM in e-commerce and the post-consumption intention, especially in emerging markets. Data was collected from 758 online customers via a web-based survey in Vietnam. Particular contribution of the results is that perceived usefulness, perceived ease of use, fairness, trust and the quality of the customer interface have direct or indirect impacts on customer satisfaction and customer loyalty. Moreover, in emerging markets, trust was outlined as the strongest factor contributing to customer satisfaction and leading to customer loyalty.

Development of electronic medical record charting for hospital-based transfusion and apheresis medicine services: Early adoption perspectives

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Rebecca Levy

2010-01-01

Full Text Available Background: Electronic medical records (EMRs provide universal access to health care information across multidisciplinary lines. In pathology departments, transfusion and apheresis medicine services (TAMS involved in direct patient care activities produce data and documentation that typically do not enter the EMR. Taking advantage of our institution′s initiative for implementation of a paperless medical record, our TAMS division set out to develop an electronic charting (e-charting strategy within the EMR. Methods: A focus group of our hospital′s transfusion committee consisting of transfusion medicine specialists, pathologists, residents, nurses, hemapheresis specialists, and information technologists was constituted and charged with the project. The group met periodically to implement e-charting TAMS workflow and produced electronic documents within the EMR (Cerner Millenium for various service line functions. Results: The interdisciplinary working group developed and implemented electronic versions of various paper-based clinical documentation used by these services. All electronic notes collectively gather and reside within a unique Transfusion Medicine Folder tab in the EMR, available to staff with access to patient charts. E-charting eliminated illegible handwritten notes, resulted in more consistent clinical documentation among staff, and provided greater real-time review/access of hemotherapy practices. No major impediments to workflow or inefficiencies have been encountered. However, minor updates and corrections to documents as well as select work re-designs were required for optimal use of e-charting by these services. Conclusion: Documentation of pathology subspecialty activities such as TAMS can be successfully incorporated into the EMR. E-charting by staff enhances communication and helps promote standardized documentation of patient care within and across service lines. Well-constructed electronic documents in the EMR may also

Uplift of the Transantarctic Mountains and the bedrock beneath the East Antarctic ice sheet

Science.gov (United States)

ten Brink, Uri S.; Hackney, R.I.; Bannister, S.; Stern, T.A.; Makovsky, Y.

1997-01-01

In recent years the Transantarctic Mountains (TAM), the largest noncontractional mountain belt in the world, have become the focus of modelers who explained their uplift by a variety of isostatic and thermal mechanisms. A problem with these models is a lack of available data to compare with model predictions. We report here the results of a 312-km-long geophysical traverse conducted in 1993/1994 in the hinterland of the TAM. Using detailed subglacial topography and gravity measurements, we confirm the origin of the TAM as a flexural uplift of the edge of East Antarctica. Using an elastic model with a free edge, we can jointly fit the topography and the gravity with a plate having an elastic thickness of 85 ?? 15 km and a preuplift elevation of 700 ?? 50 m for East Antarctica. Using a variety of evidence, we argue that the uplift is coincident with a relatively minor tectonic event of transtensional motion between East and West Antarctica during the Eocene rather than the Late Cretaceous rifting event that created the Ross Embayment. We suggest that this transtensional motion caused the continuous plate to break, which created an escarpment that significantly increased the rates of erosion and exhumation. Results from the geophysical traverse also extend our knowledge of the bedrock geology from the exposures within the TAM to the ice covered interior. Our interpretation suggests that the Ferrar flood basalts extend at least 100 km westward under the ice. The Beacon Supergroup of Paleozoic and Mesozoic sediments thins gradually under the ice and its reconstructed thickness is reminiscent of profiles of foreland basins. Finally, there is no indication in the gravity field for an incomplete rebound due to significant melting of the East Antarctic ice sheet since the last glacial period.

Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

International Nuclear Information System (INIS)

Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S.; Rouchka, Eric C.; Hill, Bradford G.; Klinge, Carolyn M.

2016-01-01

Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

International Nuclear Information System (INIS)

Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

2014-01-01

Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma

Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice

Science.gov (United States)

Li, Qun; Zhang, Weiwei; Ke, Fang; Leng, Qibin; Wang, Hong; Chen, Jinfei; Wang, Honglin

2011-01-01

Background Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. Methodology/Principal Findings CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3GFP+) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. Conclusions/Significance TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model. PMID:21559338

INTENSI MAHASISWA YOGYAKARTA BERWIRAUSAHA BERBASIS TEKNOLOGI INFORMASI (TI

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Heru Kurnianto Tjahjono

2015-11-01

Full Text Available AbstractThe purpose of this study is to investigate intention to be entrepreneur among university students in Yogyakarta. Based on modification of TPB (theory of planned behavior and TAM (technology acceptance model, this research specifically examined whether entrepreneur’s personality is an important antecedent to explain attitude, risk perception and subjective norm of entrepreneur based on information technology (IT. This research tested whether attitude, risk perception and subjective norm of entrepreneur based on IT are important predictors to explain students’ intention to become entrepreneur based on IT. This research is a replication model proposed by Tjahjono and Palupi (2014. The samples in this research were 300 students from four large universities in Yogyakarta with purposive technique and were analyzed using structural equation modeling (SEM. The results of this research showed that attitude, risk perception, and subjective norm are consequences of entrepreneur’s personality and at the same time as antecedents to explain students’ intentions to be entrepreneur based on IT.Keywords: TPB, TAM and students intention to be entrepreneur.AbstrakPenelitian ini bertujuan untuk menginvestigasi intensi mahasiswa di Yogyakarta berwirausaha. Berbasis pada modifikasi TPB (theory of planned behavior dan TAM (technology acceptance model, penelitian ini secara spesifik menguji apakah kepribadian berwirausaha merupakan anteseden penting dalam menjelaskan sikap, persepsi resiko dan norma subjektif berwirausaha yang berbasis TI. Selanjutnya apakah sikap, persepsi resiko dan norma subjektif berwirausaha berbasis TI adalah prediktor penting dalam menjelaskan intensi mahasiswa berwirausaha yang berbasis TI. Penelitian ini merupakan replikasi model yang diajukan Tjahjono dan Palupi (2014. Sampel dalam penelitian ini adalah 300 mahasiswa 4 perguruan tinggi besar di Yogyakarta dengan teknik penyampelan secara purposive. Penelitian ini dianalisis

Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Radde, Brandie N.; Ivanova, Margarita M.; Mai, Huy Xuan; Alizadeh-Rad, Negin; Piell, Kellianne; Van Hoose, Patrick; Cole, Marsha P.; Muluhngwi, Penn; Kalbfleisch, Ted S. [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Rouchka, Eric C. [Bioinformatics and Biomedical Computing Laboratory, Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292 (United States); Hill, Bradford G. [Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States); Klinge, Carolyn M., E-mail: carolyn.klinge@louisville.edu [Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292 (United States)

2016-09-10

Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway.

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Wang, Yongmei; Cheng, Zhiqiang; Elalieh, Hashem Z; Nakamura, Eiichiro; Nguyen, Minh-Thanh; Mackem, Susan; Clemens, Thomas L; Bikle, Daniel D; Chang, Wenhan

2011-07-01

Systemic derangements and perinatal death of generalized insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) knockout mice preclude definitive assessment of IGF-1R actions in growth-plate (GP) chondrocytes. We generated cartilage-specific Igf1r knockout ((Cart) Igf1r(-/-)) mice to investigate local control of chondrocyte differentiation in the GP by this receptor. These mice died shortly after birth and showed disorganized chondrocyte columns, delayed ossification and vascular invasion, decreased cell proliferation, increased apoptosis, and increased expression of parathyroid hormone-related protein (Pthrp) RNA and protein in their GPs. The increased Pthrp expression in the knockout GPs likely was due to an increase in gene transcription, as determined by the increased activity of a LacZ reporter that was inserted downstream of the endogenous PTHrP promoter and bred into the knockout mice. To circumvent the early death of (Cart) Igf1r(-/-) mice and investigate the role of IGF-1R during postnatal growth, we made tamoxifen (Tam)-inducible, cartilage-specific Igf1r knockout ((TamCart) Igf1r(-/-)) mice. At 2 weeks of age and 7 to 8 days after Tam injection, the (TamCart) Igf1r(-/-) mice showed growth retardation with a disorganized GP, reduced chondrocyte proliferation, decreased type 2 collagen and Indian Hedgehog (Ihh) expression, but increased expression of PTHrP. Consistent with in vivo observations, in vitro knockout of the Igf1r gene by adenoviral expression of Cre recombinase suppressed cell proliferation, promoted apoptosis, and increased Pthrp expression. Our data indicate that the IGF-1R in chondrocytes controls cell growth, survival, and differentiation in embryonic and postnatal GPs in part by suppression of Pthrp expression. Copyright © 2011 American Society for Bone and Mineral Research.

Modeling the impact of a carbon tax: A trial analysis for Washington State

International Nuclear Information System (INIS)

Mori, Keibun

2012-01-01

In recent years, energy policy makers have proposed a carbon tax as an economy-wide policy tool to curb greenhouse gas (GHG) emissions. The quantification of its impact on GHG emissions has relied on an energy-economy model, whose complexity often makes it difficult to comprehend how it simulates the interaction of a carbon tax and energy demand. This study therefore aims at developing an alternative model called the Carbon Tax Analysis Model (C-TAM). The elasticity-based approach used in C-TAM is less sophisticated than an equilibrium-based approach used in an energy-economy model, but C-TAM is designed to maximize its predictive capabilities by using a wide range of elasticities for each sector and fuel use, accounting for likely changes in fuel mix for electricity generation, and addressing the model's sensitivity to elasticity estimates with Monte Carlo simulation. The trial analysis in this study evaluates a potential carbon tax in Washington State, suggesting a carbon tax at US$30 per metric ton of CO 2 (tCO 2 ) lowers GHG emissions by 8.4% from the business-as-usual (BAU) scenario in 2035. The study concludes that C-TAM can provide meaningful policy implications by forecasting detailed impact on revenues and energy demand for each sector and fuel use. - Highlights: ► An elasticity-based model is developed to forecast the impact of a carbon tax. ► This model can show detailed impacts on each sector and fuel use. ► Extensive literature review and sensitivity analyses cover the model's weakness. ► A carbon tax is effective in curbing greenhouse gas emissions in Washington State. ► A carbon tax is however more effective if implemented nationwide.

CBP Time and Attendance Management

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Department of Homeland Security — The TAMS, supports time and attendance (payroll), overtime cap monitoring, overtime scheduling functions, budget reporting, staffing level reporting, and a variety...

Transient absorption microscopy studies of energy relaxation in graphene oxide thin film.

Science.gov (United States)

Murphy, Sean; Huang, Libai

2013-04-10

Spatial mapping of energy relaxation in graphene oxide (GO) thin films has been imaged using transient absorption microscopy (TAM). Correlated AFM images allow us to accurately determine the thickness of the GO films. In contrast to previous studies, correlated TAM-AFM allows determination of the effect of interactions of GO with the substrate and between stacked GO layers on the relaxation dynamics. Our results show that energy relaxation in GO flakes has little dependence on the substrate, number of stacked layers, and excitation intensity. This is in direct contrast to pristine graphene, where these factors have great consequences in energy relaxation. This suggests intrinsic factors rather than extrinsic ones dominate the excited state dynamics of GO films.

Chen-Nester-Tung quasi-local energy and Wang-Yau quasi-local mass

Science.gov (United States)

Liu, Jian-Liang; Yu, Chengjie

2017-10-01

In this paper, we show that the Chen-Nester-Tung (CNT) quasi-local energy with 4D isometric matching references is closely related to the Wang-Yau (WY) quasi-local energy. As a particular example, we compute the second variation of the CNT quasi-local energy for axially symmetric Kerr-like spacetimes with axially symmetric embeddings at the obvious critical point (0 , 0) and find that it is a saddle critical point in most of the cases. Also, as a byproduct, we generalize a previous result about the coincidence of the CNT quasi-local energy and Brown-York mass for axially symmetric Kerr-like spacetimes by Tam and the first author Liu and Tam (2016) to general spacetimes.

Evaluation for computerized axial tomography to three anthropomorphic methods to estimate the thigh muscle area

International Nuclear Information System (INIS)

Fernandez Vieitez, Jorge Alberto; Alvarez Cuesta, Jose Alberto; Williams Wilson, Luis

2001-01-01

Three anthropometric methods to estimate the thigh muscle area (TMA, cm) were evaluated. Seventeen young males were taken as a sample. The TMA was estimated by using the formulas of Gurney-Jellife, Jones-Pearson, Housh, and others. In the same place where the measurements of circumferences and skinfolds were made, the TAM was determined by computerized axial tomography. It was used as a reference criterion with which the anthropometric values were compared. The methods of Gurney-Jellife and Jones-Pearson significantly overestimated the TAM obtained by CAT (9.0 + - 12.8 cm 2 [4.4 %]; p = 0.01 and 22.0 + - 14.9 cm 2 [10.9 %]; p = 1.6 . 10-5, respectively), whereas that of Housh and others underestimated the values of CAT (-48.8 + - 11.7 cm 2 [24.1 %]; p = 9.4 . 10-12). The Gurney-Jellife equation was the only one that proved to be interchangeable with CAT, on obtaining a coefficient of correlation (r) and a slope of regression (b) for the difference and the average between both methods that were not statistically significant (r 0,421; b = 0,21 + - 0.12, p = 0.09). It was concluded that of the 3 studied anthropometric methods, the Gurney-Jellife method offers the most accurate TAM values

Constraints on lateral gene transfer in promoting fimbrial usher protein diversity and function.

Science.gov (United States)

Stubenrauch, Christopher J; Dougan, Gordon; Lithgow, Trevor; Heinz, Eva

2017-11-01

Fimbriae are long, adhesive structures widespread throughout members of the family Enterobacteriaceae. They are multimeric extrusions, which are moved out of the bacterial cell through an integral outer membrane protein called usher. The complex folding mechanics of the usher protein were recently revealed to be catalysed by the membrane-embedded translocation and assembly module (TAM). Here, we examine the diversity of usher proteins across a wide range of extraintestinal (ExPEC) and enteropathogenic (EPEC) Escherichia coli , and further focus on a so far undescribed chaperone-usher system, with this usher referred to as UshC. The fimbrial system containing UshC is distributed across a discrete set of EPEC types, including model strains like E2348/67, as well as ExPEC ST131, currently the most prominent multi-drug-resistant uropathogenic E. coli strain worldwide. Deletion of the TAM from a naive strain of E. coli results in a drastic time delay in folding of UshC, which can be observed for a protein from EPEC as well as for two introduced proteins from related organisms, Yersinia and Enterobacter We suggest that this models why the TAM machinery is essential for efficient folding of proteins acquired via lateral gene transfer. © 2017 The Authors.

RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

Science.gov (United States)

Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

2017-01-01

According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

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Yi-Rang Na

Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

Science.gov (United States)

Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

2017-11-01

Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

Probing the active site of MIO-dependent 2,3-aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites

Science.gov (United States)

Bruner, Steven D.; Cooke, Heather

2012-01-01

The tyrosine aminomutase SgTAM produces (S)-β-tyrosine from l-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form α,β-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been no reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the α,β-unsaturated intermediates to form β-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray co-crystal structure of the SgTAM mutant of the catalytic base with l-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis. PMID:20577998

The Effects of Technology Innovativeness and System Exposure on Student Acceptance of E-textbooks

Directory of Open Access Journals (Sweden)

Madison N. Ngafeeson

2015-01-01

Full Text Available The efforts of educators in the last three decades have, among other things, focused on the use of information technology (IT in education. It has become commonplace to view information systems both as an effective carrier of course content as well as a cost-effective tool to improve student learning outcomes. One of such technologies is the e-book. Decision-makers in the education field need make sense of this technological transformation. However, despite the growing popularity of e-books in higher education, its adoption by students is yet to be crystalized. This study exploits the technology acceptance model (TAM framework to examine student acceptance of e-textbooks as “internally” impacted by technology innovativeness and “externally” influenced by system exposure. The results showed that students’ technology innovativeness is associated with student acceptance of e-textbooks and that system exposure was a strong moderator of the TAM relationships. The findings suggest that students’ openness to new technology, in general, is likely to positively affect the adoption of a specific new instructional technology. Additionally, system exposure was found to be a significant moderator of the TAM relationships. It is concluded that students’ technology innovativeness and system exposure must therefore be factored into instructional technology usage decision-making models.

Assessment of Metabolic Changes in Mycobacterium smegmatis Wild-Type and alr Mutant Strains: Evidence of a New Pathway of d-Alanine Biosynthesis.

Science.gov (United States)

Marshall, Darrell D; Halouska, Steven; Zinniel, Denise K; Fenton, Robert J; Kenealy, Katie; Chahal, Harpreet K; Rathnaiah, Govardhan; Barletta, Raúl G; Powers, Robert

2017-03-03

In mycobacteria, d-alanine is an essential precursor for peptidoglycan biosynthesis. The only confirmed enzymatic pathway to form d-alanine is through the racemization of l-alanine by alanine racemase (Alr, EC 5.1.1.1). Nevertheless, the essentiality of Alr in Mycobacterium tuberculosis and Mycobacterium smegmatis for cell survivability in the absence of d-alanine has been a point of controversy with contradictory results reported in the literature. To address this issue, we examined the effects of alr inactivation on the cellular metabolism of M. smegmatis. The M. smegmatis alr insertion mutant TAM23 exhibited essentially identical growth to wild-type mc 2 155 in the absence of d-alanine. NMR metabolomics revealed drastically distinct phenotypes between mc 2 155 and TAM23. A metabolic switch was observed for TAM23 as a function of supplemented d-alanine. In the absence of d-alanine, the metabolic response directed carbon through an unidentified transaminase to provide the essential d-alanine required for survival. The process is reversed when d-alanine is available, in which the d-alanine is directed to peptidoglycan biosynthesis. Our results provide further support for the hypothesis that Alr is not an essential function of M. smegmatis and that specific Alr inhibitors will have no bactericidal action.

Reversing Age Related Changes of the Laryngeal Muscles by Chronic Electrostimulation of the Recurrent Laryngeal Nerve.

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Michael Karbiener

Full Text Available Age related atrophy of the laryngeal muscles -mainly the thyroarytenoid muscle (TAM- leads to a glottal gap and consequently to a hoarse and dysphonic voice that significantly affects quality of life. The aim of our study was to reverse this atrophy by inducing muscular hypertrophy by unilateral functional electrical stimulation (FES of the recurrent laryngeal nerve (RLN in a large animal model using aged sheep (n = 5. Suitable stimulation parameters were determined by fatiguing experiments of the thyroarytenoid muscle in an acute trial. For the chronic trial an electrode was placed around the right RLN and stimulation was delivered once daily for 29 days. We chose a very conservative stimulation pattern, total stimulation time was two minutes per day, or 0.14% of total time. Overall, the mean muscle fiber diameter of the stimulated right TAM was significantly larger than the non-stimulated left TAM (30μm±1.1μm vs. 28μm±1.1 μm, p<0.001. There was no significant shift in fiber type distribution as judged by immunohistochemistry. The changes of fiber diameter could not be observed in the posterior cricoarytenoid muscle (PCAM. FES is a possible new treatment option for reversing the effects of age related laryngeal muscle atrophy.

[Intoxications specific to the Aquitaine region].

Science.gov (United States)

Bédry, R; Gromb, S

2009-07-01

Some intoxications are more specifically linked to the Aquitaine region than to other regions of France, due to environmental circumstances (fauna, flora, climate) or traditional activities (gastronomy). Three types of intoxications are particular in this area. Pine processionary caterpillar envenomations (Thaumetopoea pityocampa), a Southern Europe pinewood parasite, are frequently encountered in the Landes' forest. They are responsible of ocular and/or skin lesions with urticaria or contact dermatitis, seldom associated with immediate IgE hypersensitivity. According to the south Atlantic coastal region geology and the marine streams, venomous marine animals are mainly located in Charente-Maritime for jellyfish, in Gironde and in Landes for weeverfish and in Atlantic Pyrenees for sea anemone. Usually not dangerous, first-aid workers treat most cases of these envenomations. Some endemic mushrooms (Tricholoma auratum) which grow on the dunes of the Atlantic coastal region, are usually considered as very good comestibles, but were recently responsible for serious intoxications: T.auratum was responsible of several cases of rhabdomyolysis, without neurological involvement, nor renal or hepatic lesion. Three deaths were notified. Animal studies confirmed the responsibility of the mushrooms.

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

Directory of Open Access Journals (Sweden)

Mahin Khatami

2014-01-01

dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2 and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine, facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-b, PGE2. M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9 is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin and tumorigenic (Yang properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

Energy Technology Data Exchange (ETDEWEB)

Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

2014-01-27

dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health.

Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

International Nuclear Information System (INIS)

Khatami, Mahin

2014-01-01

dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune system and effective preventive and therapeutic approaches and accurate risk assessment toward improvement of public health

Efficacy and safety of tamsulosin hydrochloride 0.2 mg and combination of tamsulosin hydrochloride 0.2 mg plus solifenacin succinate 5 mg after transurethral resection of the prostate: a prospective, randomized controlled trial

Directory of Open Access Journals (Sweden)

Shin YS

2016-09-01

Full Text Available Yu Seob Shin,1,* Li Tao Zhang,1,* Jae Hyung You,1 In Sung Choi,1 Chen Zhao,2 Jong Kwan Park1 1Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Medical Device Clinical Trial Center of Chonbuk National University, Jeonju, Republic of Korea; 2Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to evaluate the safety and efficacy of tamsulosin hydrochloride 0.2 mg (TAM and its combination with solifenacin succinate 5 mg (SOL after transurethral resection of the prostate (TURP.Patients and methods: The patients were randomized into three groups: TURP (group 1, TURP plus TAM (group 2, and TURP plus TAM + SOL (group 3. Patients in group 2 and group 3 received medication for 4 weeks. The primary efficacy end points were the mean change in total International Prostate Symptom Score (IPSS and IPSS subscores. The secondary end points included quality-of-life score, Overactive Bladder Symptom Score, and short-form voiding and storage score of International Continence Society.Results: In total, 37 men (31.8% in group 1, 37 men (31.8% in group 2, and 42 men (36.2% in group 3 completed the study. In total IPSS, no significant improvement was seen from baseline to the end of treatment in groups 2 and 3 compared with group 1. However, in group 2, the decrement in the IPSS storage score was smaller than group 1 (P=0.02, and in group 3, the decrement in the IPSS voiding score was smaller than group 1 (P=0.05. In groups 2 and 3 compared with group 1, improvements in the quality of life score, total score of Overactive Bladder Symptom Score, and short-form voiding score and storage score of International Continence Society were not statistically

Assimilation and subcellular partitioning of elements by grass shrimp collected along an impact gradient

International Nuclear Information System (INIS)

Seebaugh, David R.; Wallace, William G.

2009-01-01

Chronic exposure to polluted field conditions can impact metal bioavailability in prey and may influence metal transfer to predators. The present study investigated the assimilation of Cd, Hg and organic carbon by grass shrimp Palaemonetes pugio, collected along an impact gradient within the New York/New Jersey Harbor Estuary. Adult shrimp were collected from five Staten Island, New York study sites, fed 109 Cd- or 203 Hg-labeled amphipods or 14 C-labeled meals and analyzed for assimilation efficiencies (AE). Subsamples of amphipods and shrimp were subjected to subcellular fractionation to isolate metal associated with a compartment presumed to contain trophically available metal (TAM) (metal associated with heat-stable proteins [HSP - e.g., metallothionein-like proteins], heat-denatured proteins [HDP - e.g., enzymes] and organelles [ORG]). TAM- 109 Cd% and TAM- 203 Hg% in radiolabeled amphipods were ∼64% and ∼73%, respectively. Gradients in AE- 109 Cd% (∼54% to ∼75%) and AE- 203 Hg% (∼61% to ∼78%) were observed for grass shrimp, with the highest values exhibited by shrimp collected from sites within the heavily polluted Arthur Kill complex. Population differences in AE- 14 C% were not observed. Assimilated 109 Cd% partitioned to the TAM compartment in grass shrimp varied between ∼67% and ∼75%. 109 Cd bound to HSP in shrimp varied between ∼15% and ∼47%, while 109 Cd associated with metal-sensitive HDP was ∼17% to ∼44%. Percentages of assimilated 109 Cd bound to ORG were constant at ∼10%. Assimilated 203 Hg% associated with TAM in grass shrimp did not exhibit significant variation. Percentages of assimilated 203 Hg bound to HDP (∼47%) and ORG (∼11%) did not vary among populations and partitioning of 203 Hg to HSP was not observed. Using a simplified biokinetic model of metal accumulation from the diet, it is estimated that site-specific variability in Cd AE by shrimp and tissue Cd burdens in field-collected prey (polychaetes Nereis spp

Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

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Euphemia Yee Leung

2014-09-01

Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

Extraction - spectrophotometric determination of tantalum (V) with 2-(2-thiazolylazo)-5-dimethylaminophenol and 1,3-diphenylguanidine

International Nuclear Information System (INIS)

Tsurumi, C.; Furuya, K.; Kamada, H.

1981-01-01

Tantalum(V)-2-(2-thiazolylazo)-5-dimethylaminophenol (TAM) chelate anion is extracted quantitatively into benzyl alcohol with 1,3-diphenylguanidine (DPG) to form a ternary complex. In the organic phase, the complex has an absorption maximum at 605 nm. The optimum pH range for the extraction is 4.1 to 4.9 and the ternary complex is stable for at least 50 min. Beer's law is obeyed over a concentration range of 2 to 18 μg of tantalum(V) in 10 ml of the organic phase. The molar absorptivity of the ternary complex is 4.1 x 10 4 l mol -1 at 605 nm. The composition of the ternary complex is considered to be (TaO 2 ) 2 (TAM) 3 (DPG + ). (author)

131I labeling of tamoxifen and biodistribution studies in rats

International Nuclear Information System (INIS)

Biber Muftuler, F.Z.; Unak, P.; Teksoz, S.; Acar, C.; Yolcular, S.; Yuerekli, Y.

2008-01-01

Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131 I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue

An extension of the technology acceptance model for business intelligence systems: project management maturity perspective

Directory of Open Access Journals (Sweden)

Mirjana Pejić Bach

2017-01-01

Full Text Available Business intelligence systems (BISs refer to wide range of technologies and applications useful for retrieving and analyzing the large amount of information with the goal to generate knowledge useful for making effective business decision. In order to investigate adoption of BISs in companies, we propose a model based on the technology acceptance model (TAM that is expanded by variables representing the concept of a project management maturity (PMM. The survey on the sample of USA companies has been conducted with the chief information officer (CIO as the main informant. Structural equations model has been developed in order to test the research model. Results indicate that TAM expanded with the notion of PMM is useful in increasing understanding of BISs adoption in companies.

Turizm pazarlamasında görsel ve yazılı tanıtım materyali içeriğinin satın alma niyetine etkileri: Eksik bilgiye dayalı çıkarım yaklaşımı

OpenAIRE

Bilim, Yasin

2010-01-01

Tanıtım ve pazarlama alanındaki çalışmalarda, reklamda verilen bilgilerin reklamı yapılan destinasyonu tam anlamıyla yansıtabildiğini varsayılmaktadır. Bununla birlikte, destinasyonlar nadiren tam bilgiyle tanıtılmakta ve bu yüzden tüketiciler genel olarak satın alma kararını sınırlı bilgiye dayandırarak vermektedirler. Eksik bilgi, 'karar vermek için gerekli olan ürün özelliklerinden bir ya da birkaçının olmaması' olarak tanımlanmaktadır. Bilginin eksikliği yaygın bir durumdur. Yapılan bir a...

Genetic improvement of soybean through induced mutagenesis

International Nuclear Information System (INIS)

Manjaya, J.G.; Nandanwar, R.S.; Thengane, R.J.; Muthiah, A.R.

2009-01-01

Soybean (Glycine max (L.) Merril) is one of the important oilseed crops of India. The country produces more than 9.00 million tonnes of soybean per annum and has acquired first place amongst oilseed crops grown in India. Narrow genetic base of cultivated varieties in soybean is of global concern. Efficient mutant production systems, through physical or chemical mutagenesis, have been well established in soybean. A vast amount of genetic variability, of both quantitative and qualitative traits, has been generated through experimental mutagenesis. Two soybean varieties TAMS-38 and TAMS 98-21 have been developed and released for commercial cultivation by Bhabha Atomic Research Centre (BARC). In this paper the role of mutation breeding in soybean improvement has been discussed. (author)

Coppers context, and conjoints: a reassessment of TAM

NARCIS (Netherlands)

Bouwman, Harry; van de Wijngaert, Lidwien

2009-01-01

This study examines the role and explanatory value of context-, task- and information-related characteristics vis-a-vis individual characteristics in relation with respect to the adoption of mobile technologies and applications. We combine insights from adoption and acceptance literature with media

Kto tam shagajet levoi? Pravoi! Pravoi! / Oleg Samorodni

Index Scriptorium Estoniae

Samorodni, Oleg, 1961-

2006-01-01

Faktum & Ariko poolt läbi viidud uuringust selgus, et Eesti elanikud eelistavad Riigikogu valimistel hääletada pigem parempoolsete parteide poolt. Autor analüüsib parem- ja vasakpoolsete parteide ideoloogia olemust Eesti ühiskonnas

TenCompetence Assessment Model (TAM), ver 1.0

NARCIS (Netherlands)

Petrov, Milen; Aleksieva-Petrova, Adelina

2007-01-01

The software is available as an open source product through the TENCompetence Sourceforge software project repository. Available under the three clause BSD licence, Copyright TENCompetence Foundation.

The influence of relationship intention on cell phone users' attitudes ...

African Journals Online (AJOL)

Kirstam

2014-09-01

Sep 1, 2014 ... all customers are receptive to relationship marketing strategies; only some customers ... be managed throughout the service experience (Sharma, Tam & Kim 2012: 531), ..... This approach is appropriate, as the service.

75 FR 24997 - FPL Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 1 and 2; Environmental Assessment...

Science.gov (United States)

2010-05-06

... proposed action is necessary to correct a typographical error in Appendix C which incorrectly labels the... day of April 2010. For the Nuclear Regulatory Commission. Peter S. Tam, Senior Project Manager, Plant...

An Evaluation of GeoBEST Contingency Beddown Planning Software Using the Technology Acceptance Model

National Research Council Canada - National Science Library

Jensen, Shawn

2002-01-01

.... The Technology Acceptance Model (TAM) was applied, which measures a prospective user's perceptions of the technology's usefulness and ease-of-use and predicts their intentions to use the software in the future...

Induction and inhibition of oocyte maturation by EDCs in zebrafish

Directory of Open Access Journals (Sweden)

Tokumoto Mika

2005-12-01

Full Text Available Abstract Background Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH, which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC, diethylstilbestrol (DES, a nonsteroidal estrogen. Methods In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation. Results Among agents tested, tamoxifen (TAM and its metabolite 4-hydroxytamoxifen (4-OHT showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent. Conclusion These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.

Biodegradation analyses of trichloroethylene (TCE) by bacteria and its use for biosensing of TCE.

Science.gov (United States)

Chee, Gab-Joo

2011-09-30

Trichloroethylene (TCE) is a toxic, recalcitrant groundwater pollutant. TCE-degrading microorganisms were isolated from various environments. The aerobic bacteria isolated from toluene- and tryptophan-containing media were Pseudomonas sp. strain ASA86 and Burkholderia sp. strain TAM17, respectively; these are necessary for inducing TCE biodegradation in a selective medium. The half-degradation time of TCE to a concentration of 1mg/L was 18 h for strain ASA86 and 7 days for strain TAM17. While identifying toluene/TCE degradation genes, we found that in strain ASA86, the gene was the same as the todC1 gene product encoding toluene dioxygenase identified in Pseudomonas putida F1, and that in strain TAM17, the gene was similar to the tecA1 gene product encoding chlorobenzene dioxygenase identified in Burkholderia sp. PS12. A novel TCE biosensor was developed using strain ASA86 as the inducer of toluene under aerobic conditions. The TCE biosensor exhibited a linear relationship below 3 ppm TCE. Detection limit of the biosensor was 0.05 ppm TCE. The response time of the biosensor was less than 10 min. The biosensor response displayed a constant level during a 2 day period. The TCE biosensor displayed sufficient sensitivity for monitoring TCE in environmental systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages

Science.gov (United States)

Peterson, Teresa E.; Kirkpatrick, Nathaniel D.; Huang, Yuhui; Farrar, Christian T.; Marijt, Koen A.; Kloepper, Jonas; Datta, Meenal; Amoozgar, Zohreh; Seano, Giorgio; Jung, Keehoon; Kamoun, Walid S.; Vardam, Trupti; Snuderl, Matija; Goveia, Jermaine; Chatterjee, Sampurna; Batista, Ana; Muzikansky, Alona; Leow, Ching Ching; Xu, Lei; Batchelor, Tracy T.; Duda, Dan G.; Fukumura, Dai; Jain, Rakesh K.

2016-01-01

Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits of anti-VEGF receptor (VEGFR) treatment in murine GBM models and that circulating Ang-2 levels in GBM patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could improve survival in two orthotopic models of GBM, Gl261 and U87. Dual therapy using cediranib and MEDI3617 (an anti–Ang-2–neutralizing antibody) improved survival over each therapy alone by delaying Gl261 growth and increasing U87 necrosis, effectively reducing viable tumor burden. Consistent with their vascular-modulating function, the dual therapies enhanced morphological normalization of vessels. Dual therapy also led to changes in tumor-associated macrophages (TAMs). Inhibition of TAM recruitment using an anti–colony-stimulating factor-1 antibody compromised the survival benefit of dual therapy. Thus, dual inhibition of VEGFR/Ang-2 prolongs survival in preclinical GBM models by reducing tumor burden, improving normalization, and altering TAMs. This approach may represent a potential therapeutic strategy to overcome the limitations of anti-VEGFR monotherapy in GBM patients by integrating the complementary effects of anti-Ang2 treatment on vessels and immune cells. PMID:27044097

Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

International Nuclear Information System (INIS)

Ran, Sophia; Montgomery, Kyle E.

2012-01-01

It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

External Variables as Antecedents of Users Perception in Virtual Library Usage

Directory of Open Access Journals (Sweden)

Olusola I. Akinbobola

2016-05-01

Full Text Available Several studies extended the Technology Acceptance Model (TAM by examining the antecedents of perceived usefulness and perceived ease of use; the present study looks at demographic aspect of external variables in virtual library use among undergraduate students. The purpose of this study is to identify the demographic factors sex, level of study, cumulative grade point average, and computer knowledge that act as external factors that are antecedents of perceived usefulness and perceived ease of use. The university management makes a large investment in the provision of a virtual library; investigation of the virtual library acceptance by students is important. TAM and theory of reasoned action (TRA are utilised to theoretically test a model for the extension and to predict virtual library acceptance and usage. In a survey study, data was collected by using a structured questionnaire given to 394 randomly selected participants in a private university. Data were analysed by Pearson product moment correlation, multiple and hierarchical regression. The result of the study is consistent with TAM factors examined for explaining virtual library usage. The extension model accounts for 2.5% variance in perceived usefulness, 2.1% in perceived ease of use, 11.7% - 15.2% on intention to use and 7.2% on actual use of virtual library. Implications of the findings of the study on user’s virtual library training are discussed.

Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

Science.gov (United States)

Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

2017-05-02

Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

A semi-analytical iterative technique for solving chemistry problems

Directory of Open Access Journals (Sweden)

Majeed Ahmed AL-Jawary

2017-07-01

Full Text Available The main aim and contribution of the current paper is to implement a semi-analytical iterative method suggested by Temimi and Ansari in 2011 namely (TAM to solve two chemical problems. An approximate solution obtained by the TAM provides fast convergence. The current chemical problems are the absorption of carbon dioxide into phenyl glycidyl ether and the other system is a chemical kinetics problem. These problems are represented by systems of nonlinear ordinary differential equations that contain boundary conditions and initial conditions. Error analysis of the approximate solutions is studied using the error remainder and the maximal error remainder. Exponential rate for the convergence is observed. For both problems the results of the TAM are compared with other results obtained by previous methods available in the literature. The results demonstrate that the method has many merits such as being derivative-free, and overcoming the difficulty arising in calculating Adomian polynomials to handle the non-linear terms in Adomian Decomposition Method (ADM. It does not require to calculate Lagrange multiplier in Variational Iteration Method (VIM in which the terms of the sequence become complex after several iterations, thus, analytical evaluation of terms becomes very difficult or impossible in VIM. No need to construct a homotopy in Homotopy Perturbation Method (HPM and solve the corresponding algebraic equations. The MATHEMATICA® 9 software was used to evaluate terms in the iterative process.

TEACHING 'NATURAL PRODUCT CHEMISTRY' IN TANZANIA

African Journals Online (AJOL)

Temechegn

cultural differences to chemistry learning was highlighted in a Chemistry Education ... knowledge has been blended into the course are discussed. .... was given for Traditional African Medicine (TAM): “Traditional African medicine is a.

Vice-Chancellors Influence on Academic Staff Intentions to Use ...

African Journals Online (AJOL)

kmacharia

adoption and diffusion of Learning Management System (LMS) by academic staff for ... of TAM, as a supportive framework for investigating the academic staff ... This definition includes university-wide information systems that embrace blended.

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

Energy Technology Data Exchange (ETDEWEB)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

2012-10-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

International Nuclear Information System (INIS)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

2012-01-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

International Nuclear Information System (INIS)

Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

2012-01-01

Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68 + macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer

Study of the sorption of nuclear fuel fission products using non-ion exchange polymeric and inorganic materials

International Nuclear Information System (INIS)

Manorik, P.

1997-01-01

New tetrazamacrocycle and crown-ether poly-styrene and divinylbenzenepolystyrene derivatives (P-TAM and P-CE respectively) have been synthesized and studied as chemisorbents for Cs, Sr (P-CE) and Ru, Co (P-TAM) radioisotopes. It has been found that the tetraazamacro cycle modifier concentration in such material is about 5 x 10 -4 M/g material. Model solutions, containing Ru and other platinoid salts, and also Co salts, were used in experiments at concentrations of 5 x 10 -3 - 5 x 10 -6 M/L. It was shown that P-TAM quantitatively removes Ru and other platinoids from the water solution at pH = 0-1 during 1-2 days and practically all modifying groups participate in the sorption process. It was established that in alkaline solutions this sorbent also adsorbs Co, Cr and other 3d-metal ions. P-TAM also demonstrates a very high platinoid sorption selectivity (close to 100%) from solutions containing, for example, platinoids in the presence of a large excess of 3d-metal ions. 137 Cs sorption by some types of P-CE and IN-CE from Ringer-Locka model waste solution was also studied and it was found that K d (Bq/g) strongly depends not only on the crown-ether ring size but also on the form in which crown-ethers exist on the surface, for example when the modifier was in the form of the complex such as P-CE-L(L=K 3 Fe(CN) 6 or L=K 4 Fe(CN) 6 ) there was an increase in K' d value (Bq/mole of CE). The results of a study of 85 Sr removal by P-CE and IN-CE show that the chemisorption capacity strongly depends not only on the ''hole'' size of crown-ethers but also on the nature of encapsulated complexes, including ferrocyanides of different types. 32 refs, 5 figs, 5 tabs

Operator auditory perception and spectral quantification of umbilical artery Doppler ultrasound signals.

Directory of Open Access Journals (Sweden)

Ann Thuring

Full Text Available OBJECTIVE: An experienced sonographer can by listening to the Doppler audio signals perceive various timbres that distinguish different types of umbilical artery flow despite an unchanged pulsatility index (PI. Our aim was to develop an objective measure of the Doppler audio signals recorded from fetoplacental circulation in a sheep model. METHODS: Various degrees of pathological flow velocity waveforms in the umbilical artery, similar to those in human complicated pregnancies, were induced by microsphere embolization of the placental bed (embolization model, 7 lamb fetuses, 370 Doppler recordings or by fetal hemodilution (anemia model, 4 lamb fetuses, 184 recordings. A subjective 11-step operator auditory scale (OAS was related to conventional Doppler parameters, PI and time average mean velocity (TAM, and to sound frequency analysis of Doppler signals (sound frequency with the maximum energy content [MAXpeak] and frequency band at maximum level minus 15 dB [MAXpeak-15 dB] over several heart cycles. RESULTS: WE FOUND A NEGATIVE CORRELATION BETWEEN THE OAS AND PI: median Rho -0.73 (range -0.35- -0.94 and -0.68 (range -0.57- -0.78 in the two lamb models, respectively. There was a positive correlation between OAS and TAM in both models: median Rho 0.80 (range 0.58-0.95 and 0.90 (range 0.78-0.95, respectively. A strong correlation was found between TAM and the results of sound spectrum analysis; in the embolization model the median r was 0.91 (range 0.88-0.97 for MAXpeak and 0.91 (range 0.82-0.98 for MAXpeak-15 dB. In the anemia model, the corresponding values were 0.92 (range 0.78-0.96 and 0.96 (range 0.89-0.98, respectively. CONCLUSION: Audio-spectrum analysis reflects the subjective perception of Doppler sound signals in the umbilical artery and has a strong correlation to TAM-velocity. This information might be of importance for clinical management of complicated pregnancies as an addition to conventional Doppler parameters.

Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

National Research Council Canada - National Science Library

Tsan, Min-Fu

2004-01-01

Tumor-associated macrophages (TAM) may comprise up to 50% of the tumor mass in breast cancer and are capable of producing estrogen and angiogenic cytokines that regulate the growth and angiogenesis of breast cancer...

DOE hearing on the draft area recommendation report for the Crystalline Repository Project, State House, Boston, Massachusetts, April 8, 1986: Transcript of proceedings

International Nuclear Information System (INIS)

1986-01-01

This document contains a transcript of the comments of 48 witnesses. These meetings were held to hear public comments regarding the selection of a site for a second high-level nuclear waste repository. TAM

Thermochronological Evidence for Cenozoic Segmentation of Transantarctic Mountains

Science.gov (United States)

Zattin, M.; Pace, D.; Andreucci, B.; Rossetti, F.; Talarico, F.

2013-12-01

The Transantarctic Mountains (TAM) represent the boundary between the cratonic East Antarctica and the West Antarctica and are thus related to formation of the Western Antarctic Rift system (WARS). However, temporal relationships between timing of TAM uplift and evolution of the WARS are not clear. The large amount of existing thermochronological data indicate that exhumation of the TAM occurred at different times and extents, with main cooling events in the Early Cretaceous, Late Cretaceous, and early Cenozoic. Uplift of the different segments of the TAM was not recorded according to regular trends along the mountain chain, but instead appears diachronous and without a recognizable spatial pattern. Here we present apatite fission-track (AFT) data from 20 samples, collected from metamorphic and intrusive rocks from the region comprised between the Blue Glacier and the Byrd Glacier. AFT data show a large variety of ages, ranging from 28.0 to 88.8 Ma and without a clear correlation between age and elevation. As a whole, spatial variations suggest a decrease of ages from S to the region of the Koettlitz Glacier, where ages suddenly raise up to Cretaceous values. A marked increase of ages has been detected also south of Darwin Glacier, that is in correspondence of the Britannia Range. Thermal modelling shows that cooling paths are usually composite, with a main cooling event followed by slower cooling to present day temperatures. Time of main cooling event is late Cretaceous for samples from the Britannia Range whereas it is Eocene-Oligocene for samples from Koettlitz and Mulock areas. In any case, cooling rates are always quite low also during periods of enhanced uplift, with values not exceeding 5°C/Ma. These data support the idea of tectonic block segmentation of the TAM during the last phases of exhumation. Most of vertical displacements occurred during the Oligocene across transverse fault zones such as the Discovery Accommodation Zone to the north and the

Integrating health belief model and technology acceptance model: an investigation of health-related internet use.

Science.gov (United States)

Ahadzadeh, Ashraf Sadat; Pahlevan Sharif, Saeed; Ong, Fon Sim; Khong, Kok Wei

2015-02-19

Today, people use the Internet to satisfy health-related information and communication needs. In Malaysia, Internet use for health management has become increasingly significant due to the increase in the incidence of chronic diseases, in particular among urban women and their desire to stay healthy. Past studies adopted the Technology Acceptance Model (TAM) and Health Belief Model (HBM) independently to explain Internet use for health-related purposes. Although both the TAM and HBM have their own merits, independently they lack the ability to explain the cognition and the related mechanism in which individuals use the Internet for health purposes. This study aimed to examine the influence of perceived health risk and health consciousness on health-related Internet use based on the HBM. Drawing on the TAM, it also tested the mediating effects of perceived usefulness of the Internet for health information and attitude toward Internet use for health purposes for the relationship between health-related factors, namely perceived health risk and health consciousness on health-related Internet use. Data obtained for the current study were collected using purposive sampling; the sample consisted of women in Malaysia who had Internet access. The partial least squares structural equation modeling method was used to test the research hypotheses developed. Perceived health risk (β=.135, t1999=2.676) and health consciousness (β=.447, t1999=9.168) had a positive influence on health-related Internet use. Moreover, perceived usefulness of the Internet and attitude toward Internet use for health-related purposes partially mediated the influence of health consciousness on health-related Internet use (β=.025, t1999=3.234), whereas the effect of perceived health risk on health-related Internet use was fully mediated by perceived usefulness of the Internet and attitude (β=.029, t1999=3.609). These results suggest the central role of perceived usefulness of the Internet and

Influencia del Género en la Percepción y Adopción de e-Learning en Alumnos de Educación Superior en Chile

Directory of Open Access Journals (Sweden)

Patricio Esteban Ramírez-Correa

2010-11-01

El objetivo principal de este estudio es examinar las diferencias de género en la adopción de la tecnología en los estudiantes de educación superior en Chile. El modelo TAM es la herramienta utilizada para medir la aceptación y el uso de e-learning de los encuestados. Se utilizo Partial Least Squares (PLS, específicamente, el análisis multigrupo de PLS se usó para comparar las diferencias entre grupos. En resumen, podemos afirmar que en una muestra de estudiantes chilenos de educación superior su conducta de aceptación de la tecnología de e-learning coincide con el modelo TAM y los resultados no muestran diferencias estadísticamente significativas entre mujeres y hombres.

Process Considerations for the Asymmetric Synthesis of Chiral Amines using ω-Transaminase

DEFF Research Database (Denmark)

Lima Afonso Neto, Watson

in order to eliminate infeasible routes. This work illustrates the Laboratory scale characterization of different process options for the asymmetric synthesis of chiral amines catalysed by ω-transaminase (ω –TAm). The studied process options include: (i) the immobilization of the biocatalyst to improve its...... focused on development of comprehensive screening methodologies and guidelines to aid (i) the selection and characterization of suitable biocatalysts for the process; (ii) the selection and characterization of suitable carriers for immobilization of (S)- and (R)-selective ω-TAm; and (iii) the selection...... of suitable polymeric resins for product removal. The work has been performed in collaboration with c-LEcta GmbH (Leipzig, Germany) and DSM Innovative Synthesis (Geleen, The Netherlands) who supplied the enzymes for the case study, making possible the successful demonstration of the screening methodologies...