F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner
Yumimoto, Kanae; Akiyoshi, Sayuri; Ueo, Hiroki; Sagara, Yasuaki; Onoyama, Ichiro; Ueo, Hiroaki; Ohno, Shinji; Mori, Masaki; Mimori, Koshi; Nakayama, Keiichi I.
2015-01-01
The gene encoding F-box protein FBXW7 is frequently mutated in many human cancers. Although most previous studies have focused on the tumor-suppressive capacity of FBXW7 in tumor cells themselves, we determined that FBXW7 in the host microenvironment also suppresses cancer metastasis. Deletion of Fbxw7 in murine BM-derived stromal cells induced accumulation of NOTCH and consequent transcriptional activation of Ccl2. FBXW7-deficient mice exhibited increased serum levels of the chemokine CCL2, which resulted in the recruitment of both monocytic myeloid-derived suppressor cells and macrophages, thereby promoting metastatic tumor growth. Administration of a CCL2 receptor antagonist blocked the enhancement of metastasis in FBXW7-deficient mice. Furthermore, in human breast cancer patients, FBXW7 expression in peripheral blood was associated with serum CCL2 concentration and disease prognosis. Together, these results suggest that FBXW7 antagonizes cancer development in not only a cell-autonomous manner, but also a non-cell-autonomous manner, and that modulation of the FBXW7/NOTCH/CCL2 axis may provide a potential approach to suppression of cancer metastasis. PMID:25555218
Role of the autonomic nervous system in tumorigenesis and metastasis
Magnon, Claire
2015-01-01
Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis. PMID:27308436
Role of the autonomic nervous system in tumorigenesis and metastasis.
Magnon, Claire
2015-01-01
Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis.
[Hyperthyroidism by autonomous metastasis of thyroid carcinoma (author's transl)].
Mornex, R; Pousset, G; Briere, J; Daumont, M; Paffoy, J C
1976-01-01
Nine years after surgical ablation of a trabeculo-vesicular carcinoma of the tyroid, a patient developped bone and liver metastasis. She had clinical signs of thyrotoxicosis, clear increase of blood T3 and sligh increase of T4. The TSH secretion was blocked. Exogenous TSH increased iodine uptake in the thyroid and not in the metastasis. After 2 doses of 120 mCi of 131I, she became hypothyroid, the liver was normal and the scan revealed the disappearance of uptake in thyroid and in metastasis. Such a clinical course was previously found in only 10 cases despite the frequent funcitonal differenciation of the metastasis of thyroid carcinomas.
Chen, Limo; Gibbons, Don L; Goswami, Sangeeta; Cortez, Maria Angelica; Ahn, Young-Ho; Byers, Lauren A; Zhang, Xuejun; Yi, Xiaohui; Dwyer, David; Lin, Wei; Diao, Lixia; Wang, Jing; Roybal, Jonathon; Patel, Mayuri; Ungewiss, Christin; Peng, David; Antonia, Scott; Mediavilla-Varela, Melanie; Robertson, Gordon; Suraokar, Milind; Welsh, James W; Erez, Baruch; Wistuba, Ignacio I; Chen, Lieping; Peng, Di; Wang, Shanshan; Ullrich, Stephen E; Heymach, John V; Kurie, Jonathan M; Qin, F Xiao-Feng
2014-10-28
Immunosuppression of tumour-infiltrating lymphocytes (TIL) is a common feature of advanced cancer, but its biological basis has remained obscure. We demonstrate here a molecular link between epithelial-to-mesenchymal transition (EMT) and CD8(+) TIL immunosuppression, two key drivers of cancer progression. We show that microRNA-200 (miR-200), a cell-autonomous suppressor of EMT and metastasis, targets PD-L1. Moreover, ZEB1, an EMT activator and transcriptional repressor of miR-200, relieves miR-200 repression of PD-L1 on tumour cells, leading to CD8(+) T-cell immunosuppression and metastasis. These findings are supported by robust correlations between the EMT score, miR-200 levels and PD-L1 expression in multiple human lung cancer datasets. In addition to revealing a link between EMT and T-cell dysfunction, these findings also show that ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and suggest that subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.
MDA-9/Syntenin and IGFBP-2 Promote Angiogenesis in Human Melanoma
Das, Swadesh K.; Bhutia, Sujit K.; Azab, Belal; Kegelman, Timothy P.; Peachy, Leyla; Santhekadur, Prasanna K.; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B.
2012-01-01
Melanoma differentiation associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacological approaches were employed to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, CAM assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several pro-angiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the ECM activating Src and FAK resulting in activation by phosphorylation of Akt, which induces HIF-1α. The HIF-1α activates transcription of Insulin Growth Factor Binding Protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell non-autonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (non-autonomous). PMID:23233738
Li, Chung-Pin; Buza, Elizabeth L.; Blomberg, Rachel; Govindaraju, Priya; Avery, Diana; Monslow, James; Hsiao, Michael
2017-01-01
Pancreatic ductal adenocarcinomas (PDAs) are desmoplastic and can undergo epithelial-to-mesenchymal transition to confer metastasis and chemoresistance. Studies have demonstrated that phenotypically and functionally distinct stromal cell populations exist in PDAs. Fibroblast activation protein–expressing (FAP-expressing) cells act to enhance PDA progression, while α–smooth muscle actin myofibroblasts can restrain PDA. Thus, identification of precise molecular targets that mediate the protumorigenic activity of FAP+ cells will guide development of therapy for PDA. Herein, we demonstrate that FAP overexpression in the tumor microenvironment correlates with poor overall and disease-free survival of PDA patients. Genetic deletion of FAP delayed onset of primary tumor and prolonged survival of mice in the KPC mouse model of PDA. While genetic deletion of FAP did not affect primary tumor weight in advanced disease, FAP deficiency increased tumor necrosis and impeded metastasis to multiple organs. Lineage-tracing studies unexpectedly showed that FAP is not only expressed by stromal cells, but can also be detected in a subset of CD90+ mesenchymal PDA cells, representing up to 20% of total intratumoral FAP+ cells. These data suggest that FAP may regulate PDA progression and metastasis in cell-autonomous and/or non-cell-autonomous fashions. Together, these data support pursuing FAP as a therapeutic target in PDA. PMID:28978805
Chromosomal instability drives metastasis through a cytosolic DNA response.
Bakhoum, Samuel F; Ngo, Bryan; Laughney, Ashley M; Cavallo, Julie-Ann; Murphy, Charles J; Ly, Peter; Shah, Pragya; Sriram, Roshan K; Watkins, Thomas B K; Taunk, Neil K; Duran, Mercedes; Pauli, Chantal; Shaw, Christine; Chadalavada, Kalyani; Rajasekhar, Vinagolu K; Genovese, Giulio; Venkatesan, Subramanian; Birkbak, Nicolai J; McGranahan, Nicholas; Lundquist, Mark; LaPlant, Quincey; Healey, John H; Elemento, Olivier; Chung, Christine H; Lee, Nancy Y; Imielenski, Marcin; Nanjangud, Gouri; Pe'er, Dana; Cleveland, Don W; Powell, Simon N; Lammerding, Jan; Swanton, Charles; Cantley, Lewis C
2018-01-25
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.
Targeting tumor cell motility to prevent metastasis
Palmer, Trenis D.; Ashby, William J.; Lewis, John D.; Zijlstra, Andries
2011-01-01
Mortality and morbidity in patients with solid tumors invariably results from the disruption of normal biological function caused by disseminating tumor cells. Tumor cell migration is under intense investigation as the underlying cause of cancer metastasis. The need for tumor cell motility in the progression of metastasis has been established experimentally and is supported empirically by basic and clinical research implicating a large collection of migration-related genes. However, there are few clinical interventions designed to specifically target the motility of tumor cells and adjuvant therapy to specifically prevent cancer cell dissemination is severely limited. In an attempt to define motility targets suitable for treating metastasis, we have parsed the molecular determinants of tumor cell motility into five underlying principles including cell autonomous ability, soluble communication, cell-cell adhesion, cell-matrix adhesion, and integrating these determinants of migration on molecular scaffolds. The current challenge is to implement meaningful and sustainable inhibition of metastasis by developing clinically viable disruption of molecular targets that control these fundamental capabilities. PMID:21664937
Control of Metastatic Progression by microRNA Regulatory Networks
Pencheva, Nora; Tavazoie, Sohail F.
2015-01-01
Aberrant microRNA (miRNA) expression is a defining feature of human malignancy. Specific miRNAs have been identified as promoters or suppressors of metastatic progression. These miRNAs control metastasis through divergent or convergent regulation of metastatic gene pathways. Some miRNA regulatory networks govern cell-autonomous cancer phenotypes, while others modulate the cell-extrinsic composition of the metastatic microenvironment. The use of small RNAs as probes into the molecular and cellular underpinnings of metastasis holds promise for the identification of candidate genes for potential therapeutic intervention. PMID:23728460
Cooperativity Between Oncogenic PKC Epsilon and Pten Loss in Prostate Cancer Progression
2016-10-01
objective of our studies is to elucidate the mechanisms by which PKCε, in conjunction with Pten loss, lead to malignant transformation and metastasis...ligand for the G-protein-coupled receptor CXCR5. This led us to hypothesize that PKCε in conjunction Pten deficienty activate an autonomous autocrine
Preparing the “Soil”: The Premetastatic Niche
Kaplan, Rosandra N.; Rafii, Shahin; Lyden, David
2010-01-01
Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow–derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow–derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the “premetastatic niche,” which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception. PMID:17145848
Cunha, Stéphanie; Lin, Yi-Chun; Goossen, Elizabeth A.; DeVette, Christa I.; Albertella, Mark R.; Thomson, Stuart; Mulvihill, Mark J.; Welm, Alana L.
2017-01-01
SUMMARY Metastasis is the major cause of death in cancer patients, yet the genetic and epigenetic programs that drive metastasis are poorly understood. Here, we report an epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by the activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in the misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo. PMID:24388747
Genomics screens for metastasis genes
Yan, Jinchun; Huang, Qihong
2014-01-01
Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367
Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion
2014-10-01
Exosome Secretion PRINCIPAL INVESTIGATOR: Christine Vogel CONTRACTING ORGANIZATION: New York University, New York, NY 10012...30 Sep 2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5a. CONTRACT...NUMBER Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5b. GRANT NUMBER W81XWH-13-1-0467 5c. PROGRAM ELEMENT
McDonald, Oliver G; Li, Xin; Saunders, Tyler; Tryggvadottir, Rakel; Mentch, Samantha J; Warmoes, Marc O; Word, Anna E; Carrer, Alessandro; Salz, Tal H; Natsume, Sonoko; Stauffer, Kimberly M; Makohon-Moore, Alvin; Zhong, Yi; Wu, Hao; Wellen, Kathryn E; Locasale, Jason W; Iacobuzio-Donahue, Christine A; Feinberg, Andrew P
2017-03-01
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis.
A new semiquantitative method for evaluation of metastasis progression.
Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N
2012-01-01
Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.
Autonomic nerve development contributes to prostate cancer progression.
Magnon, Claire; Hall, Simon J; Lin, Juan; Xue, Xiaonan; Gerber, Leah; Freedland, Stephen J; Frenette, Paul S
2013-07-12
Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.
Defence R&D Canada's autonomous intelligent systems program
NASA Astrophysics Data System (ADS)
Digney, Bruce L.; Hubbard, Paul; Gagnon, Eric; Lauzon, Marc; Rabbath, Camille; Beckman, Blake; Collier, Jack A.; Penzes, Steven G.; Broten, Gregory S.; Monckton, Simon P.; Trentini, Michael; Kim, Bumsoo; Farell, Philip; Hopkin, Dave
2004-09-01
The Defence Research and Development Canada's (DRDC has been given strategic direction to pursue research to increase the independence and effectiveness of military vehicles and systems. This has led to the creation of the Autonomous Intelligent Systems (AIS) prgram and is notionally divide into air, land and marine vehicle systems as well as command, control and decision support systems. This paper presents an overarching description of AIS research issues, challenges and directions as well as a nominal path that vehicle intelligence will take. The AIS program requires a very close coordination between research and implementation on real vehicles. This paper briefly discusses the symbiotic relationship between intelligence algorithms and implementation mechanisms. Also presented are representative work from two vehicle specific research program programs. Work from the Autonomous Air Systems program discusses the development of effective cooperate control for multiple air vehicle. The Autonomous Land Systems program discusses its developments in platform and ground vehicle intelligence.
Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis.
Wang, Yifan; Zhou, Binhua P
2013-03-01
Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.
A non-cell-autonomous role for Ras signaling in C. elegans neuroblast delamination
Parry, Jean M.; Sundaram, Meera V.
2014-01-01
Receptor tyrosine kinase (RTK) signaling through Ras influences many aspects of normal cell behavior, including epithelial-to-mesenchymal transition, and aberrant signaling promotes both tumorigenesis and metastasis. Although many such effects are cell-autonomous, here we show a non-cell-autonomous role for RTK-Ras signaling in the delamination of a neuroblast from an epithelial organ. The C. elegans renal-like excretory organ is initially composed of three unicellular epithelial tubes, namely the canal, duct and G1 pore cells; however, the G1 cell later delaminates from the excretory system to become a neuroblast and is replaced by the G2 cell. G1 delamination and G2 intercalation involve cytoskeletal remodeling, interconversion of autocellular and intercellular junctions and migration over a luminal extracellular matrix, followed by G1 junction loss. LET-23/EGFR and SOS-1, an exchange factor for Ras, are required for G1 junction loss but not for initial cytoskeletal or junction remodeling. Surprisingly, expression of activated LET-60/Ras in the neighboring duct cell, but not in the G1 or G2 cells, is sufficient to rescue sos-1 delamination defects, revealing that Ras acts non-cell-autonomously to permit G1 delamination. We suggest that, similarly, oncogenic mutations in cells within a tumor might help create a microenvironment that is permissive for other cells to detach and ultimately metastasize. PMID:25371363
EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS
Lambert, Arthur W.; Pattabiraman, Diwakar R.; Weinberg, Robert A.
2016-01-01
Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and highlight the general principles of metastasis that have begun to emerge. PMID:28187288
Bankaitis, Katherine; Borriello, Lucia; Cox, Thomas; Lynch, Conor; Zijlstra, Andries; Fingleton, Barbara; Gužvić, Miodrag; Anderson, Robin; Neman, Josh
2017-04-01
During September 16th-20th 2016, metastasis experts from around the world convened for the 16th Biennial Congress of the Metastasis Research Society and 12th National Congress of the Chinese Tumor Metastasis Society in Chengdu, China to share most current data covering basic, translational, and clinical metastasis research. Presentations of the more than 40 invited speakers of the main congress and presentations from the associated Young Investigator Satellite Meeting are summarized in this report by session topic. The congress program also included three concurrent short talk sessions, an advocacy forum with Chinese and American metastatic patient advocates, a 'Meet the Professors Roundtable' session for young investigators, and a 'Meet the Editors' session with editors from Cancer Cell and Nature Cell Biology. The goal of integrating expertise and exchanging the latest findings, ideas, and practices in cancer metastasis research was achieved magnificently, thanks to the excellent contributions of many leaders in the field.
Walsh, Logan A; Alvarez, Mariano J; Sabio, Erich Y; Reyngold, Marsha; Makarov, Vladimir; Mukherjee, Suranjit; Lee, Ken-Wing; Desrichard, Alexis; Turcan, Şevin; Dalin, Martin G; Rajasekhar, Vinagolu K; Chen, Shuibing; Vahdat, Linda T; Califano, Andrea; Chan, Timothy A
2017-08-15
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Predictors of treatment use among foster mothers in an attachment-based intervention program.
Bick, Johanna; Dozier, Mary; Moore, Shannon
2012-01-01
The current study examined predictors of treatment use among 56 foster mothers who participated in an attachment-based intervention program for foster infants. Foster mothers' levels of treatment use were coded at early, middle, and late phases of the intervention program. Foster mothers' states of mind with regard to attachment predicted their understanding of the intervention session concepts. Specifically, autonomous foster mothers showed higher levels of understanding at the start of the intervention program, when compared with non-autonomous foster mothers. State of mind with regard to attachment also predicted foster mothers' levels of reflective functioning during the intervention sessions. Autonomous foster mothers showed higher levels of reflective functioning at early, middle, and late stages of the intervention program, when compared with non-autonomous foster mothers. The relevance of these findings for both treatment effectiveness and treatment delivery is discussed.
Metastasis Suppressor Genes: At the Interface Between the Environment and Tumor Cell Growth
Hurst, Douglas R.; Welch, Danny R.
2013-01-01
The molecular mechanisms and genetic programs required for cancer metastasis are sometimes overlapping, but components are clearly distinct from those promoting growth of a primary tumor. Every sequential, rate-limiting step in the sequence of events leading to metastasis requires coordinated expression of multiple genes, necessary signaling events, and favorable environmental conditions or the ability to escape negative selection pressures. Metastasis suppressors are molecules that inhibit the process of metastasis without preventing growth of the primary tumor. The cellular processes regulated by metastasis suppressors are diverse and function at every step in the metastatic cascade. As we gain knowledge into the molecular mechanisms of metastasis suppressors and cofactors with which they interact, we learn more about the process, including appreciation that some are potential targets for therapy of metastasis, the most lethal aspect of cancer. Until now, metastasis suppressors have been described largely by their function. With greater appreciation of their biochemical mechanisms of action, the importance of context is increasingly recognized especially since tumor cells exist in myriad microenvironments. In this review, we assemble the evidence that selected molecules are indeed suppressors of metastasis, collate the data defining the biochemical mechanisms of action, and glean insights regarding how metastasis suppressors regulate tumor cell communication to–from microenvironments. PMID:21199781
IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma
Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles
2016-01-01
Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663
IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.
Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles
2016-06-03
Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.
Tactical Decision Aids High Bandwidth Links Using Autonomous Vehicles
2004-01-01
1 Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) A. J. Healey, D. P. Horner, Center for Autonomous Underwater Vehicle...SUBTITLE Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6
Progress towards autonomous, intelligent systems
NASA Technical Reports Server (NTRS)
Lum, Henry; Heer, Ewald
1987-01-01
An aggressive program has been initiated to develop, integrate, and implement autonomous systems technologies starting with today's expert systems and evolving to autonomous, intelligent systems by the end of the 1990s. This program includes core technology developments and demonstration projects for technology evaluation and validation. This paper discusses key operational frameworks in the content of systems autonomy applications and then identifies major technological challenges, primarily in artificial intelligence areas. Program content and progress made towards critical technologies and demonstrations that have been initiated to achieve the required future capabilities in the year 2000 era are discussed.
Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles
2007-11-01
Tolerant Overactuated Autonomous Vehicles Casavola, A.; Garone, E. (2007) Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous ...Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Tolerant Overactuated Autonomous Vehicles 3.2 - 2 RTO-MP-AVT-145 UNCLASSIFIED/UNLIMITED Control allocation problem (CAP) - Given a virtual input v(t
2017-06-01
AUTONOMOUS CONTROL AND COLLABORATION (UTACC) HUMAN-MACHINE INTEGRATION MEASURES OF PERFORMANCE AND MEASURES OF EFFECTIVENESS by Thomas A...TACTICAL AUTONOMOUS CONTROL AND COLLABORATION (UTACC) HUMAN-MACHINE INTEGRATION MEASURES OF PERFORMANCE AND MEASURES OF EFFECTIVENESS 5. FUNDING...Tactical Autonomous Control and Collaboration (UTACC) program seeks to integrate Marines and autonomous machines to address the challenges encountered in
Scortegagna, Marzia; Cataisson, Christophe; Martin, Rebecca J.; Hicklin, Daniel J.; Schreiber, Robert D.; Yuspa, Stuart H.
2008-01-01
Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non–cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor κ B (NFκB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1–induced NFκB activation was composed of 2 elements, IκB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFκB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFα) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFα immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFκB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression. PMID:18199827
The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
Cortazar, Ana Rosa; Liu, Xiaojing; Urosevic, Jelena; Castillo-Martin, Mireia; Fernández-Ruiz, Sonia; Morciano, Giampaolo; Caro-Maldonado, Alfredo; Guiu, Marc; Zúñiga-García, Patricia; Graupera, Mariona; Bellmunt, Anna; Pandya, Pahini; Lorente, Mar; Martín-Martín, Natalia; Sutherland, James David; Sanchez-Mosquera, Pilar; Bozal-Basterra, Laura; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Berenguer, Antonio; Embade, Nieves; Ugalde-Olano, Aitziber; Lacasa-Viscasillas, Isabel; Loizaga-Iriarte, Ana; Unda-Urzaiz, Miguel; Schultz, Nikolaus; Aransay, Ana Maria; Sanz-Moreno, Victoria; Barrio, Rosa; Velasco, Guillermo; Pinton, Paolo; Cordon-Cardo, Carlos; Carracedo, Arkaitz
2016-01-01
Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator PGC1α suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is down-regulated in prostate cancer and associated to disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an Oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α-ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment. PMID:27214280
Engineering Review of ANCAUS/AVATAR: An Enabling Technology for the Autonomous Land Systems Program?
2003-12-01
technology for future Autonomous Land System (ALS) autonomous vehicles . Since 1989, forward thinking engineering has characterized the history of ANC/EUS and...technology for future autonomous vehicles and that; (2) ALS should adopt commercial/open source technology to support a new ALS architecture and (3) ALS
Xu, Xin; Zhang, Yun; Jasper, Jeff; Lykken, Erik; Alexander, Peter B; Markowitz, Geoffrey J; McDonnell, Donald P; Li, Qi-Jing; Wang, Xiao-Fan
2016-04-12
Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis and could serve as biomarkers for diagnostic purposes. To identify miRNAs that functionally suppress metastasis of TNBC, we employed a concerted approach with selecting miRNAs that display differential expression profiles from bioinformatic analyses of breast cancer patient databases and validating top candidates with functional assays using breast cancer cell lines and mouse models. We have found that miR-148a exhibits properties as a tumor suppressor as its expression is inversely correlated with the ability of both human and mouse breast cancer cells to colonize the lung in mouse xenograft tumor models. Mechanistically, miR-148a appears to suppress the extravasation process of cancer cells, likely by targeting two genes WNT1 and NRP1 in a cell non-autonomous manner. Importantly, lower expression of miR-148a is detected in higher-grade tumor samples and correlated with increased likelihood to develop metastases and poor prognosis in subsets of breast cancer patients, particularly those with TNBC. Thus, miR-148a is functionally defined as a suppressor of breast cancer metastasis and may serve as a prognostic biomarker for this disease.
Autonomy Level Specification for Intelligent Autonomous Vehicles
2003-09-01
Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6
MDA-9/syntenin and IGFBP-2 promote angiogenesis in human melanoma.
Das, Swadesh K; Bhutia, Sujit K; Azab, Belal; Kegelman, Timothy P; Peachy, Leyla; Santhekadur, Prasanna K; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B
2013-01-15
Melanoma differentiation-associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacologic approaches were used to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma, and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, chorioallantoic membrane (CAM) assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several proangiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the extracellular matrix (ECM), activating Src and FAK resulting in activation by phosphorylation of Akt, which induces hypoxia inducible factor 1-α (HIF-1α). The HIF-1α activates transcription of insulin growth factor-binding protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell nonautonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (nonautonomous).
Gómez, Montserrat García; Castañeda, Rosario; López, Vega García; Vidal, Manuel Martínez; Villanueva, Vicent; Espinosa, Mercedes Elvira
2012-01-01
Although asbestos was banned in Spain in 2001, monitoring the health of previously-exposed workers is required. In 2002 the Ministry of Health and the autonomous regions of Spain planned a health surveillance program for workers exposed to asbestos (Programa de Vigilancia de la Salud de los Trabajadores Expuestos al Amianto [PIVISTEA]) with employers' organizations, trade unions and scientific societies. The aim of this study was to evaluate the PIVISTEA to improve its effectiveness. A questionnaire with indicators for the year 2008 was sent to Spain's 17 autonomous regions, as well as to the autonomous cities of Ceuta and Melilla. The results were analyzed by evaluating the compliance of each program with the activities established by the PIVISTEA. In December 2008, a total of 22,158 workers from 14 autonomous regions and 306 companies were included in the program. The program had been started in 88% of the regions but surveillance activities remained scarce in 24%. Fifty-seven percent of the autonomous regions (69% of the total number of workers) provided the information requested. Seven autonomous regions provided data on the relationship between the diseases found and asbestos exposure. Only 5% of these diseases entitled affected individuals to receive compensation for occupational diseases. The health surveillance of workers previously exposed to asbestos in Spain, as well as medical-legal recognition of diseases caused by exposure at work, remain in adequate. Although the trend is positive, the effectiveness of many regional programs is limited, and inter-regional inequalities among affected workers have been detected. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.
The Twist Box Domain is Required for Twist1-induced Prostate Cancer Metastasis
Gajula, Rajendra P.; Chettiar, Sivarajan T.; Williams, Russell D.; Thiyagarajan, Saravanan; Kato, Yoshinori; Aziz, Khaled; Wang, Ruoqi; Gandhi, Nishant; Wild, Aaron T.; Vesuna, Farhad; Ma, Jinfang; Salih, Tarek; Cades, Jessica; Fertig, Elana; Biswal, Shyam; Burns, Timothy F.; Chung, Christine H.; Rudin, Charles M.; Herman, Joseph M.; Hales, Russell K.; Raman, Venu; An, Steven S.; Tran, Phuoc T.
2013-01-01
Twist1, a basic helix-loop-helix transcription factor, plays a key role during development and is a master regulator of the epithelial-mesenchymal transition (EMT) that promotes cancer metastasis. Structure-function relationships of Twist1 to cancer-related phenotypes are underappreciated, so we studied the requirement of the conserved Twist box domain for metastatic phenotypes in prostate cancer (PCa). Evidence suggests that Twist1 is overexpressed in clinical specimens and correlated with aggressive/metastatic disease. Therefore, we examined a transactivation mutant, Twist1-F191G, in PCa cells using in vitro assays which mimic various stages of metastasis. Twist1 overexpression led to elevated cytoskeletal stiffness and cell traction forces at the migratory edge of cells based on biophysical single-cell measurements. Twist1 conferred additional cellular properties associated with cancer cell metastasis including increased migration, invasion, anoikis resistance, and anchorage-independent growth. The Twist box mutant was defective for these Twist1 phenotypes in vitro. Importantly, we observed a high frequency of Twist1-induced metastatic lung tumors and extra-thoracic metastases in vivo using the experimental lung metastasis assay. The Twist box was required for PCa cells to colonize metastatic lung lesions and extra-thoracic metastases. Comparative genomic profiling revealed transcriptional programs directed by the Twist box that were associated with cancer progression, such as Hoxa9. Mechanistically, Twist1 bound to the Hoxa9 promoter and positively regulated Hoxa9 expression in PCa cells. Finally, Hoxa9 was important for Twist1-induced cellular phenotypes associated with metastasis. These data suggest that the Twist box domain is required for Twist1 transcriptional programs and PCa metastasis. PMID:23982216
Sun, Han; Luo, Liqun; Lal, Bachchu; Ma, Xinrong; Chen, Lieping; Hann, Christine L; Fulton, Amy M; Leahy, Daniel J; Laterra, John; Li, Min
2016-02-04
Two-pore domain potassium (K2P) channels act to maintain cell resting membrane potential--a prerequisite for many biological processes. KCNK9, a member of K2P family, is implicated in cancer, owing to its overexpression in human tumours and its ability to promote neoplastic cell survival and growth. However, KCNK9's underlying contributions to malignancy remain elusive due to the absence of specific modulators. Here we describe the development of monoclonal antibodies against the KCNK9 extracellular domain and their functional effects. We show that one antibody (Y4) with the highest affinity binding induces channel internalization. The addition of Y4 to KCNK9-expressing carcinoma cells reduces cell viability and increases cell death. Systemic administration of Y4 effectively inhibits growth of human lung cancer xenografts and murine breast cancer metastasis in mice. Evidence for Y4-mediated carcinoma cell autonomous and immune-dependent cytotoxicity is presented. Our study reveals that antibody-based KCNK9 targeting is a promising therapeutic strategy in KCNK9-expressing malignancies.
Autonomous Vehicle Systems Laboratory Research Capability Expansion Program
2017-12-03
currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. University of the Incarnate Word 4301 Broadway, Box #T-2 San Antonio...autonomous control , collaboration, and decision-making in unstructured, dynamic, and uncertain nonlinear environments for autonomous ground and air...vehicle systems. To fulfill the research goal, the PI has initiated fundamental research in the areas of autonomous rotorcraft control and
Communication and Control for Fleets of Autonomous Underwater Vehicles
2006-10-30
Washington State University (WSU) on fuzzy logic control systems [2-4] and autonomous vehicles [5-10]. The ALWSE-MC program developed at NAVSEA CSS was...rotating head sonar on crawlers as an additional sensor for navigation. We have previously investigated the use of video cameras on autonomous vehicles for...simulates autonomous vehicles performing mine reconnaissance/mapping, clearance, and surveillance in a littoral region. Three simulations were preformed
Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen
2010-06-01
In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 100%, 94.3%, 62.6%, and 43.5%, respectively. The study successfully establishes an orthotopic liver metastatic model of human primary gastric lymphoma in nude mice. The HGBL-0304 model can completely simulate the natural clinical process of primary gastric lymphoma and provides an ideal animal model for the research on the biology of metastasis and antimetastatic experimental therapies of primary gastric lymphoma.
Autonomous Attitude Determination System (AADS). Volume 1: System description
NASA Technical Reports Server (NTRS)
Saralkar, K.; Frenkel, Y.; Klitsch, G.; Liu, K. S.; Lefferts, E.; Tasaki, K.; Snow, F.; Garrahan, J.
1982-01-01
Information necessary to understand the Autonomous Attitude Determination System (AADS) is presented. Topics include AADS requirements, program structure, algorithms, and system generation and execution.
Decentralized Control of Autonomous Vehicles
2003-01-01
Autonomous Vehicles by John S. Baras, Xiaobo Tan, Pedram Hovareshti CSHCN TR 2003-8 (ISR TR 2003-14) Report Documentation Page Form ApprovedOMB No. 0704...AND SUBTITLE Decentralized Control of Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Decentralized Control of Autonomous Vehicles ∗ John S. Baras, Xiaobo Tan, and Pedram
1992-02-01
Postgraduate School Autonomous Under Vehicle (AUV) are then examined. Autonomous underwater vehicle (AUV), hard real-time system, real - time operating system , real-time programming language, real-time system, soft real-time system.
Experiments in teleoperator and autonomous control of space robotic vehicles
NASA Technical Reports Server (NTRS)
Alexander, Harold L.
1990-01-01
A research program and strategy are described which include fundamental teleoperation issues and autonomous-control issues of sensing and navigation for satellite robots. The program consists of developing interfaces for visual operation and studying the consequences of interface designs as well as developing navigation and control technologies based on visual interaction. A space-robot-vehicle simulator is under development for use in virtual-environment teleoperation experiments and neutral-buoyancy investigations. These technologies can be utilized in a study of visual interfaces to address tradeoffs between head-tracking and manual remote cameras, panel-mounted and helmet-mounted displays, and stereoscopic and monoscopic display systems. The present program can provide significant data for the development of control experiments for autonomously controlled satellite robots.
NASA Technical Reports Server (NTRS)
Hinchey, Michael G.; Rash, James L.; Rouff, Christopher A.; Gracanin, Denis; Erickson, John
2005-01-01
Requirements-to-Design-to-Code (R2D2C) is an approach to the engineering of computer-based systems that embodies the idea of requirements-based programming in system development. It goes further; however, in that the approach offers not only an underlying formalism, but full formal development from requirements capture through to the automatic generation of provably-correct code. As such, the approach has direct application to the development of systems requiring autonomic properties. We describe a prototype tool to support the method, and illustrate its applicability to the development of LOGOS, a NASA autonomous ground control system, which exhibits autonomic behavior. Finally, we briefly discuss other areas where the approach and prototype tool are being considered for application.
Lucas, Jared M.; Heinlein, Cynthia; Kim, Tom; Hernandez, Susana A.; Malik, Muzdah S.; True, Lawrence D.; Morrissey, Colm; Corey, Eva; Montgomery, Bruce; Mostaghel, Elahe; Clegg, Nigel; Coleman, Ilsa; Brown, Christopher M.; Schneider, Eric L.; Craik, Charles; Simon, Julian; Bedalov, Tony; Nelson, Peter S.
2014-01-01
TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment. PMID:25122198
Autonomous power expert system
NASA Technical Reports Server (NTRS)
Ringer, Mark J.; Quinn, Todd M.
1990-01-01
The goal of the Autonomous Power System (APS) program is to develop and apply intelligent problem solving and control technologies to the Space Station Freedom Electrical Power Systems (SSF/EPS). The objectives of the program are to establish artificial intelligence/expert system technology paths, to create knowledge based tools with advanced human-operator interfaces, and to integrate and interface knowledge-based and conventional control schemes. This program is being developed at the NASA-Lewis. The APS Brassboard represents a subset of a 20 KHz Space Station Power Management And Distribution (PMAD) testbed. A distributed control scheme is used to manage multiple levels of computers and switchgear. The brassboard is comprised of a set of intelligent switchgear used to effectively switch power from the sources to the loads. The Autonomous Power Expert System (APEX) portion of the APS program integrates a knowledge based fault diagnostic system, a power resource scheduler, and an interface to the APS Brassboard. The system includes knowledge bases for system diagnostics, fault detection and isolation, and recommended actions. The scheduler autonomously assigns start times to the attached loads based on temporal and power constraints. The scheduler is able to work in a near real time environment for both scheduling and dynamic replanning.
Autonomous power expert system
NASA Technical Reports Server (NTRS)
Ringer, Mark J.; Quinn, Todd M.
1990-01-01
The goal of the Autonomous Power System (APS) program is to develop and apply intelligent problem solving and control technologies to the Space Station Freedom Electrical Power Systems (SSF/EPS). The objectives of the program are to establish artificial intelligence/expert system technology paths, to create knowledge based tools with advanced human-operator interfaces, and to integrate and interface knowledge-based and conventional control schemes. This program is being developed at the NASA-Lewis. The APS Brassboard represents a subset of a 20 KHz Space Station Power Management And Distribution (PMAD) testbed. A distributed control scheme is used to manage multiple levels of computers and switchgear. The brassboard is comprised of a set of intelligent switchgear used to effectively switch power from the sources to the loads. The Autonomous Power Expert System (APEX) portion of the APS program integrates a knowledge based fault diagnostic system, a power resource scheduler, and an interface to the APS Brassboard. The system includes knowledge bases for system diagnostics, fault detection and isolation, and recommended actions. The scheduler autonomously assigns start times to the attached loads based on temporal and power constraints. The scheduler is able to work in a near real time environment for both scheduling an dynamic replanning.
Bronson, Sevilla
2016-09-01
In the U.S., enrollment and graduation rates of baccalaureate nursing programs are slowly increasing. Rigorous program requirements can be overwhelming for students who may have difficulty adjusting to curriculum demands. Faculty who help students to adjust may also build a supportive learning environment that promotes autonomous motivation, improves engagement, and strengthens academic performance. Students may also experience well-being and autonomy when they feel supported and when their needs are met. The aim of this study was to investigate nursing students' autonomy support environments and autonomous motivation (measured as spirituality), and the influence on engagement and academic performance. A cross-sectional correlational design using a convenience sample of 150 nursing students in the last year of a baccalaureate nursing program was used. Participants were recruited from four universities in Florida and data collection occurred over three months. All participants were enrolled in the last year of their baccalaureate nursing program with an average Grade Point Average (GPA) of 3.36. The learning climate alone was moderately supportive of student motivation (M=70.60, SD=18.99). No significant relationship between the autonomy support environment and autonomous motivation (r=.034, p=.676) was found. Correlations and regression analysis of autonomous motivation and work engagement were significant (F (2, 147)=28.28, p=.000). Comparison of participant groups from each university independently revealed supportive learning environments. Strategies to promote autonomy must be developed and implemented as a means of ensuring a favorable learning environment. Future research may include the investigation of spirituality and autonomous motivation as two separate variables. Copyright © 2016 Elsevier Ltd. All rights reserved.
Won, Young-Woong; Joo, Jungnam; Yun, Tak; Lee, Geon-Kook; Han, Ji-Youn; Kim, Heung Tae; Lee, Jin Soo; Kim, Moon Soo; Lee, Jong Mog; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Sohee
2015-05-01
Development of brain metastasis results in a significant reduction in overall survival. However, there is no an effective tool to predict brain metastasis in non-small cell lung cancer (NSCLC) patients. We conducted this study to develop a feasible nomogram that can predict metastasis to the brain as the first relapse site in patients with curatively resected NSCLC. A retrospective review of NSCLC patients who had received curative surgery at National Cancer Center (Goyang, South Korea) between 2001 and 2008 was performed. We chose metastasis to the brain as the first relapse site after curative surgery as the primary endpoint of the study. A nomogram was modeled using logistic regression. Among 1218 patients, brain metastasis as the first relapse developed in 87 patients (7.14%) during the median follow-up of 43.6 months. Occurrence rates of brain metastasis were higher in patients with adenocarcinoma or those with a high pT and pN stage. Younger age appeared to be associated with brain metastasis, but this result was not statistically significant. The final prediction model included histology, smoking status, pT stage, and the interaction between adenocarcinoma and pN stage. The model showed fairly good discriminatory ability with a C-statistic of 69.3% and 69.8% for predicting brain metastasis within 2 years and 5 years, respectively. Internal validation using 2000 bootstrap samples resulted in C-statistics of 67.0% and 67.4% which still indicated good discriminatory performances. The nomogram presented here provides the individual risk estimate of developing metastasis to the brain as the first relapse site in patients with NSCLC who have undergone curative surgery. Surveillance programs or preventive treatment strategies for brain metastasis could be established based on this nomogram. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Zhou, Zhen Ni; Sharma, Ved P.; Beaty, Brian T.; Roh-Johnson, Minna; Peterson, Esther A.; Van Rooijen, Nico; Kenny, Paraic A.; Wiley, H. Steven; Condeelis, John S.; Segall, Jeffrey E.
2013-01-01
Increased expression of HBEGF in ER negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of CSF-1 while the tumor associated macrophages (TAMs) in turn aid in tumor cell invasion by secreting EGF. To determine how the autocrine expression of EGFR ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We find that autocrine HBEGF expression enhanced in vivo intravasation and metastasis, and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of MMP2 and MMP9 expression. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling. PMID:24013225
Zhou, Z N; Sharma, V P; Beaty, B T; Roh-Johnson, M; Peterson, E A; Van Rooijen, N; Kenny, P A; Wiley, H S; Condeelis, J S; Segall, J E
2014-07-17
Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.
PRIMUS: autonomous navigation in open terrain with a tracked vehicle
NASA Astrophysics Data System (ADS)
Schaub, Guenter W.; Pfaendner, Alfred H.; Schaefer, Christoph
2004-09-01
The German experimental robotics program PRIMUS (PRogram for Intelligent Mobile Unmanned Systems) is focused on solutions for autonomous driving in unknown open terrain, over several project phases under specific realization aspects for more than 12 years. The main task of the program is to develop algorithms for a high degree of autonomous navigation skills with off-the-shelf available hardware/sensor technology and to integrate this into military vehicles. For obstacle detection a Dornier-3D-LADAR is integrated on a tracked vehicle "Digitized WIESEL 2". For road-following a digital video camera and a visual perception module from the Universitaet der Bundeswehr Munchen (UBM) has been integrated. This paper gives an overview of the PRIMUS program with a focus on the last program phase D (2001 - 2003). This includes the system architecture, the description of the modes of operation and the technology development with the focus on obstacle avoidance and obstacle classification using a 3-D LADAR. A collection of experimental results and a short look at the next steps in the German robotics program will conclude the paper.
Crane, Melissa M.; Tate, Deborah F.; Finkelstein, Eric A.; Linnan, Laura A.
2012-01-01
This analysis investigated if changes in autonomous or controlled motivation for participation in a weight loss program differed between individuals offered a financial incentive for weight loss compared to individuals not offered an incentive. Additionally, the same relationships were tested among those who lost weight and either received or did not receive an incentive. This analysis used data from a year-long randomized worksite weight loss program that randomly assigned employees in each worksite to either a low-intensity weight loss program or the same program plus small financial incentives for weight loss ($5.00 per percentage of initial weight lost). There were no differences in changes between groups on motivation during the study, however, increases in autonomous motivation were consistently associated with greater weight losses. This suggests that the small incentives used in this program did not lead to increases in controlled motivation nor did they undermine autonomous motivation. Future studies are needed to evaluate the magnitude and timing of incentives to more fully understand the relationship between incentives and motivation. PMID:22577524
NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.
Rodrigues, Paulo; Patel, Saroor A; Harewood, Louise; Olan, Ioana; Vojtasova, Erika; Syafruddin, Saiful E; Zaini, M Nazhif; Richardson, Emma K; Burge, Johanna; Warren, Anne Y; Stewart, Grant D; Saeb-Parsy, Kourosh; Samarajiwa, Shamith A; Vanharanta, Sakari
2018-06-06
Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. SIGNIFICANCE: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 1-16. ©2018 AACR. ©2018 American Association for Cancer Research.
An architecture for an autonomous learning robot
NASA Technical Reports Server (NTRS)
Tillotson, Brian
1988-01-01
An autonomous learning device must solve the example bounding problem, i.e., it must divide the continuous universe into discrete examples from which to learn. We describe an architecture which incorporates an example bounder for learning. The architecture is implemented in the GPAL program. An example run with a real mobile robot shows that the program learns and uses new causal, qualitative, and quantitative relationships.
Results of NASA's First Autonomous Formation Flying Experiment: Earth Observing-1 (EO-1)
NASA Technical Reports Server (NTRS)
Folta, David C.; Hawkins, Albin; Bauer, Frank H. (Technical Monitor)
2001-01-01
NASA's first autonomous formation flying mission completed its primary goal of demonstrating an advanced technology called enhanced formation flying. To enable this technology, the Guidance, Navigation, and Control center at the Goddard Space Flight Center (GSFC) implemented a universal 3-axis formation flying algorithm in an autonomous executive flight code onboard the New Millennium Program's (NMP) Earth Observing-1 (EO-1) spacecraft. This paper describes the mathematical background of the autonomous formation flying algorithm and the onboard flight design and presents the validation results of this unique system. Results from functionality assessment through fully autonomous maneuver control are presented as comparisons between the onboard EO-1 operational autonomous control system called AutoCon(tm), its ground-based predecessor, and a standalone algorithm.
Automation and robotics technology for intelligent mining systems
NASA Technical Reports Server (NTRS)
Welsh, Jeffrey H.
1989-01-01
The U.S. Bureau of Mines is approaching the problems of accidents and efficiency in the mining industry through the application of automation and robotics to mining systems. This technology can increase safety by removing workers from hazardous areas of the mines or from performing hazardous tasks. The short-term goal of the Automation and Robotics program is to develop technology that can be implemented in the form of an autonomous mining machine using current continuous mining machine equipment. In the longer term, the goal is to conduct research that will lead to new intelligent mining systems that capitalize on the capabilities of robotics. The Bureau of Mines Automation and Robotics program has been structured to produce the technology required for the short- and long-term goals. The short-term goal of application of automation and robotics to an existing mining machine, resulting in autonomous operation, is expected to be accomplished within five years. Key technology elements required for an autonomous continuous mining machine are well underway and include machine navigation systems, coal-rock interface detectors, machine condition monitoring, and intelligent computer systems. The Bureau of Mines program is described, including status of key technology elements for an autonomous continuous mining machine, the program schedule, and future work. Although the program is directed toward underground mining, much of the technology being developed may have applications for space systems or mining on the Moon or other planets.
ERIC Educational Resources Information Center
Wang, Jihui
2010-01-01
The studies on autonomous learning based on the theories of constructivism and the advantages of technology propose valuable ideas for modern teaching theories and practices. In this paper, we put forward ways and methods in developing learner awareness, learning strategies and habits of autonomous learning in Henan College of Finance and Taxation…
STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.
Priego, Neibla; Zhu, Lucía; Monteiro, Cátia; Mulders, Manon; Wasilewski, David; Bindeman, Wendy; Doglio, Laura; Martínez, Liliana; Martínez-Saez, Elena; Cajal, Santiago Ramón Y; Megías, Diego; Hernández-Encinas, Elena; Blanco-Aparicio, Carmen; Martínez, Lola; Zarzuela, Eduardo; Muñoz, Javier; Fustero-Torres, Coral; Pineiro, Elena; Hernández-Laín, Aurelio; Bertero, Luca; Poli, Valeria; Sánchez-Martínez, Melchor; Menendez, Javier A; Soffietti, Riccardo; Bosch-Barrera, Joaquim; Valiente, Manuel
2018-06-11
The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment that confine brain metastasis without infiltrating the lesion. Here, we describe that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by signal transducer and activator of transcription 3 (STAT3) in a subpopulation of reactive astrocytes surrounding metastatic lesions. These reactive astrocytes benefit metastatic cells by their modulatory effect on the innate and acquired immune system. In patients, active STAT3 in reactive astrocytes correlates with reduced survival from diagnosis of intracranial metastases. Blocking STAT3 signaling in reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We also show that a safe and orally bioavailable treatment that inhibits STAT3 exhibits significant antitumor effects in patients with advanced systemic disease that included brain metastasis. Responses to this therapy were notable in the central nervous system, where several complete responses were achieved. Given that brain metastasis causes substantial morbidity and mortality, our results identify a novel treatment for increasing survival in patients with secondary brain tumors.
Preliminary Results of NASA's First Autonomous Formation Flying Experiment: Earth Observing-1 (EO-1)
NASA Technical Reports Server (NTRS)
Folta, David; Hawkins, Albin
2001-01-01
NASA's first autonomous formation flying mission is completing a primary goal of demonstrating an advanced technology called enhanced formation flying. To enable this technology, the Guidance, Navigation, and Control center at the Goddard Space Flight Center has implemented an autonomous universal three-axis formation flying algorithm in executive flight code onboard the New Millennium Program's (NMP) Earth Observing-1 (EO-1) spacecraft. This paper describes the mathematical background of the autonomous formation flying algorithm and the onboard design and presents the preliminary validation results of this unique system. Results from functionality assessment and autonomous maneuver control are presented as comparisons between the onboard EO-1 operational autonomous control system called AutoCon(tm), its ground-based predecessor, and a stand-alone algorithm.
Autonomous Mission Manager for Rendezvous, Inspection and Mating
NASA Technical Reports Server (NTRS)
Zimpfer, Douglas J.
2003-01-01
To meet cost and safety objectives, space missions that involve proximity operations between two vehicles require a high level of autonomy to successfully complete their missions. The need for autonomy is primarily driven by the need to conduct complex operations outside of communication windows, and the communication time delays inherent in space missions. Autonomy also supports the goals of both NASA and the DOD to make space operations more routine, and lower operational costs by reducing the requirement for ground personnel. NASA and the DoD have several programs underway that require a much higher level of autonomy for space vehicles. NASA's Space Launch Initiative (SLI) program has ambitious goals of reducing costs by a factor or 10 and improving safety by a factor of 100. DARPA has recently begun its Orbital Express to demonstrate key technologies to make satellite servicing routine. The Air Force's XSS-ll program is developing a protoflight demonstration of an autonomous satellite inspector. A common element in space operations for many NASA and DOD missions is the ability to rendezvous, inspect anclJor dock with another spacecraft. For DARPA, this is required to service or refuel military satellites. For the Air Force, this is required to inspect un-cooperative resident space objects. For NASA, this is needed to meet the primary SLI design reference mission of International Space Station re-supply. A common aspect for each of these programs is an Autonomous Mission Manager that provides highly autonomous planning, execution and monitoring of the rendezvous, inspection and docking operations. This paper provides an overview of the Autonomous Mission Manager (AMM) design being incorporated into many of these technology programs. This AMM provides a highly scalable level of autonomous operations, ranging from automatic execution of ground-derived plans to highly autonomous onboard planning to meet ground developed mission goals. The AMM provides the capability to automatically execute the plans and monitor the system performance. In the event of system dispersions or failures the AMM can modify plans or abort to assure overall system safety. This paper describes the design and functionality of Draper's AMM framework, presents concept of operations associated with the use of the AMM, and outlines the relevant features of the flight demonstrations.
JOMAR: Joint Operations with Mobile Autonomous Robots
2015-12-21
AFRL-AFOSR-JP-TR-2015-0009 JOMAR: Joint Operations with Mobile Autonomous Robots Edwin Olson UNIVERSITY OF MICHIGAN Final Report 12/21/2015...SUBTITLE JOMAR: Joint Operations with Mobile Autonomous Robots 5a. CONTRACT NUMBER FA23861114024 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...14. ABSTRACT Under this grant, we formulated and implemented a variety of novel algorithms that address core problems in multi- robot systems. These
Autonomous benthic algal cultivator under feedback control of ecosystem metabolism
USDA-ARS?s Scientific Manuscript database
An autonomous and internally-controlled techno-ecological hybrid was developed that controls primary production of algae in a laboratory-scale cultivator. The technoecosystem is based on an algal turf scrubber (ATS) system that combines engineered feedback control programming with internal feedback...
Theseus: tethered distributed robotics (TDR)
NASA Astrophysics Data System (ADS)
Digney, Bruce L.; Penzes, Steven G.
2003-09-01
The Defence Research and Development Canada's (DRDC) Autonomous Intelligent System's program conducts research to increase the independence and effectiveness of military vehicles and systems. DRDC-Suffield's Autonomous Land Systems (ALS) is creating new concept vehicles and autonomous control systems for use in outdoor areas, urban streets, urban interiors and urban subspaces. This paper will first give an overview of the ALS program and then give a specific description of the work being done for mobility in urban subspaces. Discussed will be the Theseus: Thethered Distributed Robotics (TDR) system, which will not only manage an unavoidable tether but exploit it for mobility and navigation. Also discussed will be the prototype robot called the Hedgehog, which uses conformal 3D mobility in ducts, sewer pipes, collapsed rubble voids and chimneys.
Development for SSV on a parallel processing system (PARAGON)
NASA Astrophysics Data System (ADS)
Gothard, Benny M.; Allmen, Mark; Carroll, Michael J.; Rich, Dan
1995-12-01
A goal of the surrogate semi-autonomous vehicle (SSV) program is to have multiple vehicles navigate autonomously and cooperatively with other vehicles. This paper describes the process and tools used in porting UGV/SSV (unmanned ground vehicle) autonomous mobility and target recognition algorithms from a SISD (single instruction single data) processor architecture (i.e., a Sun SPARC workstation running C/UNIX) to a MIMD (multiple instruction multiple data) parallel processor architecture (i.e., PARAGON-a parallel set of i860 processors running C/UNIX). It discusses the gains in performance and the pitfalls of such a venture. It also examines the merits of this processor architecture (based on this conceptual prototyping effort) and programming paradigm to meet the final SSV demonstration requirements.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, Z. N.; Sharma, V. P.; Beaty, B. T.
2014-10-13
Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and inmore » particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.« less
Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen
2010-06-01
To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.
Baseline Motivation Type as a Predictor of Dropout in a Healthy Eating Text Messaging Program.
Coa, Kisha; Patrick, Heather
2016-09-29
Growing evidence suggests that text messaging programs are effective in facilitating health behavior change. However, high dropout rates limit the potential effectiveness of these programs. This paper describes patterns of early dropout in the HealthyYou text (HYTxt) program, with a focus on the impact of baseline motivation quality on dropout, as characterized by Self-Determination Theory (SDT). This analysis included 193 users of HYTxt, a diet and physical activity text messaging intervention developed by the US National Cancer Institute. Descriptive statistics were computed, and logistic regression models were run to examine the association between baseline motivation type and early program dropout. Overall, 43.0% (83/193) of users dropped out of the program; of these, 65.1% (54/83; 28.0% of all users) did so within the first 2 weeks. Users with higher autonomous motivation had significantly lower odds of dropping out within the first 2 weeks. A one unit increase in autonomous motivation was associated with lower odds (odds ratio 0.44, 95% CI 0.24-0.81) of early dropout, which persisted after adjusting for level of controlled motivation. Applying SDT-based strategies to enhance autonomous motivation might reduce early dropout rates, which can improve program exposure and effectiveness.
AltiVec performance increases for autonomous robotics for the MARSSCAPE architecture program
NASA Astrophysics Data System (ADS)
Gothard, Benny M.
2002-02-01
One of the main tall poles that must be overcome to develop a fully autonomous vehicle is the inability of the computer to understand its surrounding environment to a level that is required for the intended task. The military mission scenario requires a robot to interact in a complex, unstructured, dynamic environment. Reference A High Fidelity Multi-Sensor Scene Understanding System for Autonomous Navigation The Mobile Autonomous Robot Software Self Composing Adaptive Programming Environment (MarsScape) perception research addresses three aspects of the problem; sensor system design, processing architectures, and algorithm enhancements. A prototype perception system has been demonstrated on robotic High Mobility Multi-purpose Wheeled Vehicle and All Terrain Vehicle testbeds. This paper addresses the tall pole of processing requirements and the performance improvements based on the selected MarsScape Processing Architecture. The processor chosen is the Motorola Altivec-G4 Power PC(PPC) (1998 Motorola, Inc.), a highly parallized commercial Single Instruction Multiple Data processor. Both derived perception benchmarks and actual perception subsystems code will be benchmarked and compared against previous Demo II-Semi-autonomous Surrogate Vehicle processing architectures along with desktop Personal Computers(PC). Performance gains are highlighted with progress to date, and lessons learned and future directions are described.
Self-determination theory and weight loss in a Diabetes Prevention Program translation trial.
Trief, Paula M; Cibula, Donald; Delahanty, Linda M; Weinstock, Ruth S
2017-06-01
We examined self-determination theory (SDT) and weight loss, and hypothesized that the Diabetes Prevention Program's (DPP) intervention would result in an increase in autonomous regulation of motivation (AR) in participants. Further, that those with higher AR, and those who perceived educators as supporting SDT-defined needs, would lose more weight. Support, Health Information, Nutrition and Exercise (SHINE) Study data (N = 257) were analyzed. SHINE was a randomized, controlled DPP translation trial (2-years, telephonic, primary care staff). Autonomous motivation in males increased significantly, while females showed no change. Males with high AR, but not females, lost more weight. However, the significance of these relationships varied over time. Participants who perceived educators as more supportive of psychological needs lost more weight (especially males). However, effect of support on weight loss was not mediated by AR change. Autonomous motivation and educator support are relevant to male weight loss. Future research might develop interventions to enhance autonomous motivation and educator support, and understand change pathways.
1992-10-29
These people try to make their robotic vehicle as intelligent and autonomous as possible with the current state of technology. The robot only interacts... Robotics Peter J. Burt David Sarnoff Research Center Princeton, NJ 08543-5300 U.S.A. The ability of an operator to drive a remotely piloted vehicle depends...RESUPPLY - System which can rapidly and autonomously load and unload palletized ammunition. (18) AUTONOMOUS COMBAT EVACUATION VEHICLE - Robotic arms
CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction
Hermann, Gerlinda E.; Van Meter, Montina J.; Rogers, Richard C.
2014-01-01
The chemokine receptor, CXCR4, plays an essential role in guiding neural development of the CNS. Its natural agonist, CXCL12 [or stromal cell-derived factor-1 (SDF-1)], normally is derived from stromal cells, but is also produced by damaged and virus-infected neurons and glia. Pathologically, this receptor is critical to the proliferation of the HIV virus and initiation of metastatic cell growth in the brain. Anorexia, nausea and failed autonomic regulation of gastrointestinal (GI) function cause morbidity and contribute to the mortality associated with these disease states. Our previous work on the peripheral cytokine, tumor necrosis factor-alpha, demonstrated that similar morbidity factors involving GI dysfunction are attributable to agonist action on neural circuit elements of the dorsal vagal complex (DVC) of the hindbrain. The DVC includes vagal afferent terminations in the solitary nucleus, neurons in the solitary nucleus (NST) and area postrema, and visceral efferent motor neurons in the dorsal motor nucleus (DMN) that are responsible for the neural regulation of digestive functions from the oral cavity to the transverse colon. Immunohistochemical techniques demonstrate a dense concentration of CXCR4 receptors on neurons throughout the DVC and the hypoglossal nucleus. CXCR4-immunoreactivity is also intense on microglia within the DVC, though not on the astrocytes. Physiological studies show that nanoinjection of SDF-1 into the DVC produces a significant reduction in gastric motility in parallel with an elevation in the numbers of cFOS-activated neurons in the NST and DMN. These results suggest that this chemokine receptor may contribute to autonomically mediated pathophysiological events associated with CNS metastasis and infection. PMID:18333961
NASA Technical Reports Server (NTRS)
Sandy, Michael
2015-01-01
The Regolith Advanced Surface Systems Operations Robot (RASSOR) Phase 2 is an excavation robot for mining regolith on a planet like Mars. The robot is programmed using the Robotic Operating System (ROS) and it also uses a physical simulation program called Gazebo. This internship focused on various functions of the program in order to make it a more professional and efficient robot. During the internship another project called the Smart Autonomous Sand-Swimming Excavator was worked on. This is a robot that is designed to dig through sand and extract sample material. The intern worked on programming the Sand-Swimming robot, and designing the electrical system to power and control the robot.
Stress management at the worksite: reversal of symptoms profile and cardiovascular dysregulation.
Lucini, Daniela; Riva, Silvano; Pizzinelli, Paolo; Pagani, Massimo
2007-02-01
Work stress may increase cardiovascular risk either indirectly, by inducing unhealthy life styles, or directly, by affecting the autonomic nervous system and arterial pressure. We hypothesized that, before any apparent sign of disease, work-related stress is already accompanied by alterations of RR variability profile and that a simple onsite stress management program based on cognitive restructuring and relaxation training could reduce the level of stress symptoms, revert stress-related autonomic nervous system dysregulation, and lower arterial pressure. We compared 91 white-collar workers, enrolled at a time of work downsizing (hence, in a stress condition), with 79 healthy control subjects. Psychological profiles were assessed by questionnaires and autonomic nervous system regulation by spectral analysis of RR variability. We also tested a simple onsite stress management program (cognitive restructuring and relaxation training) in a subgroup of workers compared with a sham subgroup (sham program). Workers presented an elevated level of stress-related symptoms and an altered variability profile as compared with control subjects (low-frequency component of RR variability was, respectively, 65.2+/-2 versus 55.3+/-2 normalized units; P<0.001; opposite changes were observed for the high-frequency component). These alterations were largely reverted (low-frequency component of RR variability from 63.6+/-3.9 to 49.3+/-3 normalized units; P<0.001) by the stress management program, which also slightly lowered systolic arterial pressure. No changes were observed in the sham program group. This noninvasive study indicates that work stress is associated with unpleasant symptoms and with an altered autonomic profile and suggests that a stress management program could be implemented at the worksite, with possible preventive advantages for hypertension.
Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun
2018-03-01
Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status. The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis. The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. Copyright © 2018 Elsevier Ltd. All rights reserved.
Kirenskaya, Anna V; Novototsky-Vlasov, Vladimir Y; Chistyakov, Andrey N; Zvonikov, Vyacheslav M
2011-04-01
Subjective scoring and autonomic variables (heart rate, skin conduction span) were used to verify the reality of inner experience during recollection of emotionally neutral, positive, and negative past events in 19 high (HH) and 12 low (LH) hypnotizable subjects in hypnotic and nonhypnotic experimental sessions. Also, the influence of hypnotizability on the effectiveness of an imagery-based neurolinguistic programming (NLP) technique was evaluated. Results demonstrated that subjective scores of image vividness and emotional intensity were significantly higher in the HH subjects compared to LH in both sessions. The past-events recollection was followed by increased autonomic activity only in the HH subjects. The NLP procedure was followed by decreased negative emotional intensity in both groups, but autonomic activity decline was observed in the HH subjects and not in the LH.
Expert system isssues in automated, autonomous space vehicle rendezvous
NASA Technical Reports Server (NTRS)
Goodwin, Mary Ann; Bochsler, Daniel C.
1987-01-01
The problems involved in automated autonomous rendezvous are briefly reviewed, and the Rendezvous Expert (RENEX) expert system is discussed with reference to its goals, approach used, and knowledge structure and contents. RENEX has been developed to support streamlining operations for the Space Shuttle and Space Station program and to aid definition of mission requirements for the autonomous portions of rendezvous for the Mars Surface Sample Return and Comet Nucleus Sample return unmanned missions. The experience with REMEX to date and recommendations for further development are presented.
Autonomous Control Capabilities for Space Reactor Power Systems
NASA Astrophysics Data System (ADS)
Wood, Richard T.; Neal, John S.; Brittain, C. Ray; Mullens, James A.
2004-02-01
The National Aeronautics and Space Administration's (NASA's) Project Prometheus, the Nuclear Systems Program, is investigating a possible Jupiter Icy Moons Orbiter (JIMO) mission, which would conduct in-depth studies of three of the moons of Jupiter by using a space reactor power system (SRPS) to provide energy for propulsion and spacecraft power for more than a decade. Terrestrial nuclear power plants rely upon varying degrees of direct human control and interaction for operations and maintenance over a forty to sixty year lifetime. In contrast, an SRPS is intended to provide continuous, remote, unattended operation for up to fifteen years with no maintenance. Uncertainties, rare events, degradation, and communications delays with Earth are challenges that SRPS control must accommodate. Autonomous control is needed to address these challenges and optimize the reactor control design. In this paper, we describe an autonomous control concept for generic SRPS designs. The formulation of an autonomous control concept, which includes identification of high-level functional requirements and generation of a research and development plan for enabling technologies, is among the technical activities that are being conducted under the U.S. Department of Energy's Space Reactor Technology Program in support of the NASA's Project Prometheus. The findings from this program are intended to contribute to the successful realization of the JIMO mission.
A new model for programming software in body sensor networks.
de A Barbosa, Talles M G; Sene, Iwens G; da Rocha, Adson F; de O Nascimento, Francisco A A; Carvalho, Joao L A; Carvalho, Hervaldo S
2007-01-01
A Body Sensor Network (BSN) must be designed to work autonomously. On the other hand, BSNs need mechanisms that allow changes in their behavior in order to become a clinically useful tool. The purpose of this paper is to present a new programming model that will be useful for programming BSN sensor nodes. This model is based on an intelligent intermediate-level compiler. The main purpose of the proposed compiler is to increase the efficiency in system use, and to increase the lifetime of the application, considering its requirements, hardware possibilities and specialist knowledge. With this model, it is possible to maintain the autonomous operation capability of the BSN and still offer tools that allow users with little grasp on programming techniques to program these systems.
Experiments with a small behaviour controlled planetary rover
NASA Technical Reports Server (NTRS)
Miller, David P.; Desai, Rajiv S.; Gat, Erann; Ivlev, Robert; Loch, John
1993-01-01
A series of experiments that were performed on the Rocky 3 robot is described. Rocky 3 is a small autonomous rover capable of navigating through rough outdoor terrain to a predesignated area, searching that area for soft soil, acquiring a soil sample, and depositing the sample in a container at its home base. The robot is programmed according to a reactive behavior control paradigm using the ALFA programming language. This style of programming produces robust autonomous performance while requiring significantly less computational resources than more traditional mobile robot control systems. The code for Rocky 3 runs on an eight bit processor and uses about ten k of memory.
Chambers, A F
1999-02-01
The Metastasis Research Society (MRS) has held its International Congress every two years since 1986, and alternates between European and North American meeting venues. The next MRS International Congress will be held in London, UK in the year 2000, and will be hosted by the current MRS President, Dr. Suzanne Eccles (Institute of Cancer Research, Sutton, UK). Dr. Eccles took over from the out-going President, Dr. William Stetler-Stevenson (National Institutes of Health, Bethesda, MD, USA), at the San Diego meeting. Information on joining the Metastasis Research Society, which includes a subscription to the Society's journal, Clinical and Experimental Metastasis, can be obtained from Dr. Eccles (suzan@icr.ac.uk) or from the newly-elected Secretary/Treasurer Dr. Danny Welch (Hershey, PA, USA; drw9@psu.edu). The meeting was organized by Darwin Medical Communications Ltd (Gill Heaton, Oxford, UK), who have placed the full program on the meeting web site (http:@www.sparks.co.uk/mrs). It is envisaged that full abstracts of all the presentations will be placed on the Metastasis Research Society web site, which is currently under construction. Corporate sponsors for the San Diego meeting included Agouron Pharmaceuticals, Becton Dickinson & Co, Zeneca Pharma SA, Schering AG, AntiCancer Inc, Oncogene Research Products, Daiichi Seiyaku Co Ltd and Novartis Pharma AG.
NASA Astrophysics Data System (ADS)
Rainville, L.; Farrar, J. T.; Shcherbina, A.; Centurioni, L. R.
2017-12-01
The Salinity Processes in the Upper-ocean Regional Study (SPURS) is a program aimed at understanding the patterns and variability of sea surface salinity. Following the first SPURS program in an evaporation-dominated region (2012-2013), the SPURS-2 program targeted wide range of spatial and temporal scales associated with processes controlling salinity in the rain-dominated Eastern Pacific Fresh Pool. Autonomous instruments were delivered in August and September 2016 using research vessels conducted observations over one complete annual cycle. The SPURS-2 field program used coordinated observations from many different autonomous platforms, and a mix of Lagrangian and Eulerian approaches. Here we discuss the motivation, implementation, and the early of SPURS-2.
Autonomous formation flying sensor for the Star Light Mission
NASA Technical Reports Server (NTRS)
Aung, M.; Purcell, G.; Tien, J.; Young, L.; Srinivasan, J.; Ciminera, M. A.; Chong, Y. J.; Amaro, L. R.; Young, L. E.
2002-01-01
The StarLight Mission, an element of NASA's Origins Program, was designed for first-time demonstration of two technologies: formation flying optical interferometry between spacecraft and autonomous precise formation flying of an array of spacecraft to support optical interferometry. The design overview and results of the technology effort are presented in this paper.
Assessing Plankton and Particles with an Autonomous Imaging LOPC
2007-09-30
been modified to operate autonomously by auto-starting its programs on power-up and storing its data to an onboard flashcard . Since data transfer to... flashcard is a slow process, storage will occur when the AUV surfaces for a position fix. Data acquisition will commence as the AUV descends >5m
2012-03-05
DISTRIBUTION A: Approved for public release; distribution is unlimited. Program Trends •Trust in Autonomous Systems • Cross - cultural Trust...Trust & trustworthiness are independent (Mayer et al, 1995) •Trust is relational •Humans in cross - cultural interactions •Complex human-machine...Interpersonal Trustworthiness •Ability •Benevolence •Integrity Trust Metrics Cross - Cultural Trust Issues Human-Machine Interactions Autonomous
Autonomous Student Experiences in Outdoor and Adventure Education
ERIC Educational Resources Information Center
Daniel, Brad; Bobilya, Andrew J.; Kalisch, Kenneth R.; McAvoy, Leo H.
2014-01-01
This article explores the current state of knowledge regarding the use of autonomous student experiences (ASE) in outdoor and adventure education (OAE) programs. ASE are defined as components (e.g., solo, final expedition) in which participants have a greater measure of choice and control over the planning, execution, and outcomes of their…
Autonomous Rendezvous and Docking Conference, volume 2
NASA Technical Reports Server (NTRS)
1990-01-01
Autonomous Rendezvous and Docking (ARD) will be a requirement for future space programs. Clear examples include satellite servicing, repair, recovery, and reboost in the near term, and the longer range lunar and planetary exploration programs. ARD will permit more aggressive unmanned space activities, while providing a valuable operational capability for manned missions. The purpose of the conference is to identify the technologies required for an on-orbit demonstration of ARD, assess the maturity of those technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.
Animation of Traffic through Roundabouts
DOT National Transportation Integrated Search
1998-01-14
This report describes work done on a roundabout animation program during 1997. The roundabout animation program began as an undergraduate class project and has evolved to its current state. The program is based on the principle of an autonomous agent...
Turning a remotely controllable observatory into a fully autonomous system
NASA Astrophysics Data System (ADS)
Swindell, Scott; Johnson, Chris; Gabor, Paul; Zareba, Grzegorz; Kubánek, Petr; Prouza, Michael
2014-08-01
We describe a complex process needed to turn an existing, old, operational observatory - The Steward Observatory's 61" Kuiper Telescope - into a fully autonomous system, which observers without an observer. For this purpose, we employed RTS2,1 an open sourced, Linux based observatory control system, together with other open sourced programs and tools (GNU compilers, Python language for scripting, JQuery UI for Web user interface). This presentation provides a guide with time estimates needed for a newcomers to the field to handle such challenging tasks, as fully autonomous observatory operations.
Autonomous power management and distribution
NASA Technical Reports Server (NTRS)
Dolce, Jim; Kish, Jim
1990-01-01
The goal of the Autonomous Power System program is to develop and apply intelligent problem solving and control to the Space Station Freedom's electric power testbed being developed at NASA's Lewis Research Center. Objectives are to establish artificial intelligence technology paths, craft knowledge-based tools and products for power systems, and integrate knowledge-based and conventional controllers. This program represents a joint effort between the Space Station and Office of Aeronautics and Space Technology to develop and demonstrate space electric power automation technology capable of: (1) detection and classification of system operating status, (2) diagnosis of failure causes, and (3) cooperative problem solving for power scheduling and failure recovery. Program details, status, and plans will be presented.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gosnell, Thomas B.; Chavez, Joseph R.; Rowland, Mark S.
2014-02-26
RadID is a new gamma-ray spectrum analysis program for rapid screening of HPGe gamma-ray data to reveal the presence of radionuclide signatures. It is an autonomous, rule-based heuristic system that can identify well over 200 radioactive sources with particular interest in uranium and plutonium characteristics. It executes in about one second. RadID does not require knowledge of the detector efficiency, the source-to-detector distance, or the geometry of the inspected radiation source—including any shielding. In this first of a three-document series we sketch the RadID program’s origin, its minimal requirements, the user experience, and the program operation.
Opfermann, Justin D.; Leonard, Simon; Decker, Ryan S.; Uebele, Nicholas A.; Bayne, Christopher E.; Joshi, Arjun S.; Krieger, Axel
2017-01-01
This paper specifies a surgical robot performing semi-autonomous electrosurgery for tumor resection and evaluates its accuracy using a visual servoing paradigm. We describe the design and integration of a novel, multi-degree of freedom electrosurgical tool for the smart tissue autonomous robot (STAR). Standardized line tests are executed to determine ideal cut parameters in three different types of porcine tissue. STAR is then programmed with the ideal cut setting for porcine tissue and compared against expert surgeons using open and laparoscopic techniques in a line cutting task. We conclude with a proof of concept demonstration using STAR to semi-autonomously resect pseudo-tumors in porcine tissue using visual servoing. When tasked to excise tumors with a consistent 4mm margin, STAR can semi-autonomously dissect tissue with an average margin of 3.67 mm and a standard deviation of 0.89mm. PMID:29503760
NASA Astrophysics Data System (ADS)
Lane, Gerald R.
1999-07-01
To provide an overview of Tank-Automotive Robotics. The briefing will contain program overviews & inter-relationships and technology challenges of TARDEC managed unmanned and robotic ground vehicle programs. Specific emphasis will focus on technology developments/approaches to achieve semi- autonomous operation and inherent chassis mobility features. Programs to be discussed include: DemoIII Experimental Unmanned Vehicle (XUV), Tactical Mobile Robotics (TMR), Intelligent Mobility, Commanders Driver Testbed, Collision Avoidance, International Ground Robotics Competition (ICGRC). Specifically, the paper will discuss unique exterior/outdoor challenges facing the IGRC competing teams and the synergy created between the IGRC and ongoing DoD semi-autonomous Unmanned Ground Vehicle and DoT Intelligent Transportation System programs. Sensor and chassis approaches to meet the IGRC challenges and obstacles will be shown and discussed. Shortfalls in performance to meet the IGRC challenges will be identified.
Van Soom, Carolien; Donche, Vincent
2014-01-01
The low success rate of first-year college students in Science, Technology, Engineering, and Mathematics (STEM) programs has spurred many academic achievement studies in which explanatory factors are studied. In this study, we investigated from a person-oriented perspective whether different motivational and academic self-concept profiles could be discerned between male and female first-year college students in STEM and whether differences in early academic achievement were associated with these student groups. Data on autonomous motivation, academic self-concept, and early academic achievement of 1,400 first-year STEM college students were collected. Cluster analyses were used to distinguish motivational profiles based on the relative levels of autonomous motivation and academic self-concept for male and female students. Differences in early academic achievement of the various profiles were studied by means of ANCOVA. Four different motivational profiles were discerned based on the dimensions of autonomous motivation (A) and academic self-concept (S): students scoring high and respectively low on both dimensions (HA-HS or LA-LS), and students scoring high on one dimension and low on the other (HA-LS or LA-HS). Also gender differences were found in this study: male students with high levels of academic self-concept and autonomous motivation had higher academic achievement compared to male students with low levels on both motivational dimensions. For female students, motivational profiles were not associated with academic achievement. The findings partially confirm the internal and external validity of the motivational theories underpinning this study and extend the present insights on identifying subgroup(s) of at risk students in contemporary STEM programs at university level.
Van Soom, Carolien; Donche, Vincent
2014-01-01
The low success rate of first-year college students in Science, Technology, Engineering, and Mathematics (STEM) programs has spurred many academic achievement studies in which explanatory factors are studied. In this study, we investigated from a person-oriented perspective whether different motivational and academic self-concept profiles could be discerned between male and female first-year college students in STEM and whether differences in early academic achievement were associated with these student groups. Data on autonomous motivation, academic self-concept, and early academic achievement of 1,400 first-year STEM college students were collected. Cluster analyses were used to distinguish motivational profiles based on the relative levels of autonomous motivation and academic self-concept for male and female students. Differences in early academic achievement of the various profiles were studied by means of ANCOVA. Four different motivational profiles were discerned based on the dimensions of autonomous motivation (A) and academic self-concept (S): students scoring high and respectively low on both dimensions (HA-HS or LA-LS), and students scoring high on one dimension and low on the other (HA-LS or LA-HS). Also gender differences were found in this study: male students with high levels of academic self-concept and autonomous motivation had higher academic achievement compared to male students with low levels on both motivational dimensions. For female students, motivational profiles were not associated with academic achievement. The findings partially confirm the internal and external validity of the motivational theories underpinning this study and extend the present insights on identifying subgroup(s) of at risk students in contemporary STEM programs at university level. PMID:25390942
Comparison of three control methods for an autonomous vehicle
NASA Astrophysics Data System (ADS)
Deshpande, Anup; Mathur, Kovid; Hall, Ernest
2010-01-01
The desirability and challenge of developing a completely autonomous vehicle and the rising need for more efficient use of energy by automobiles motivate this research- a study for an optimum solution to computer control of energy efficient vehicles. The purpose of this paper is to compare three control methods - mechanical, hydraulic and electric that have been used to convert an experimental all terrain vehicle to drive by wire which would eventually act as a test bed for conducting research on various technologies for autonomous operation. Computer control of basic operations in a vehicle namely steering, braking and speed control have been implemented and will be described in this paper. The output from a 3 axis motion controller is used for this purpose. The motion controller is interfaced with a software program using WSDK (Windows Servo Design Kit) as an intermediate tuning layer for tuning and parameter settings in autonomous operation. The software program is developed in C++. The voltage signal sent to the motion controller can be varied through the control program for desired results in controlling the steering motor, activating the hydraulic brakes and varying the vehicle's speed. The vehicle has been tested for its basic functionality which includes testing of street legal operations and also a 1000 mile test while running in a hybrid mode. The vehicle has also been tested for control when it is interfaced with devices such as a keyboard, joystick and sensors under full autonomous operation. The vehicle is currently being tested in various safety studies and is being used as a test bed for experiments in control courses and research studies. The significance of this research is in providing a greater understanding of conventional driving controls and the possibility of improving automobile safety by removing human error in control of a motor vehicle.
Davis, Faith G.; Dolecek, Therese A.; McCarthy, Bridget J.; Villano, John L.
2012-01-01
Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States. PMID:22898372
Davis, Faith G; Dolecek, Therese A; McCarthy, Bridget J; Villano, John L
2012-09-01
Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States.
Development and flight test of a deployable precision landing system
NASA Technical Reports Server (NTRS)
Sim, Alex G.; Murray, James E.; Neufeld, David C.; Reed, R. Dale
1994-01-01
A joint NASA Dryden Flight Research Facility and Johnson Space Center program was conducted to determine the feasibility of the autonomous recovery of a spacecraft using a ram-air parafoil system for the final stages of entry from space that included a precision landing. The feasibility of this system was studied using a flight model of a spacecraft in the generic shape of a flattened biconic that weighed approximately 150 lb and was flown under a commercially available, ram-air parachute. Key elements of the vehicle included the Global Positioning System guidance for navigation, flight control computer, ultrasonic sensing for terminal altitude, electronic compass, and onboard data recording. A flight test program was used to develop and refine the vehicle. This vehicle completed an autonomous flight from an altitude of 10,000 ft and a lateral offset of 1.7 miles that resulted in a precision flare and landing into the wind at a predetermined location. At times, the autonomous flight was conducted in the presence of winds approximately equal to vehicle airspeed. Several novel techniques for computing the winds postflight were evaluated. Future program objectives are also presented.
HERMIES-3: A step toward autonomous mobility, manipulation, and perception
NASA Technical Reports Server (NTRS)
Weisbin, C. R.; Burks, B. L.; Einstein, J. R.; Feezell, R. R.; Manges, W. W.; Thompson, D. H.
1989-01-01
HERMIES-III is an autonomous robot comprised of a seven degree-of-freedom (DOF) manipulator designed for human scale tasks, a laser range finder, a sonar array, an omni-directional wheel-driven chassis, multiple cameras, and a dual computer system containing a 16-node hypercube expandable to 128 nodes. The current experimental program involves performance of human-scale tasks (e.g., valve manipulation, use of tools), integration of a dexterous manipulator and platform motion in geometrically complex environments, and effective use of multiple cooperating robots (HERMIES-IIB and HERMIES-III). The environment in which the robots operate has been designed to include multiple valves, pipes, meters, obstacles on the floor, valves occluded from view, and multiple paths of differing navigation complexity. The ongoing research program supports the development of autonomous capability for HERMIES-IIB and III to perform complex navigation and manipulation under time constraints, while dealing with imprecise sensory information.
Dobrenis, Kostantin; Gauthier, Laurent R; Barroca, Vilma; Magnon, Claire
2015-02-15
The hematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has a role in proliferation, differentiation and migration of the myeloid lineage and in mobilizing hematopoietic stem and progenitor cells into the bloodstream. However, G-CSF has been newly characterized as a neurotrophic factor in the brain. We recently uncovered that autonomic nerve development in the tumor microenvironment participates actively in prostate tumorigenesis and metastasis. Here, we found that G-CSF constrains cancer to grow and progress by, respectively, supporting the survival of sympathetic nerve fibers in 6-hydroxydopamine-sympathectomized mice and also, promoting the aberrant outgrowth of parasympathetic nerves in transgenic or xenogeneic prostate tumor models. This provides insight into how neurotrophic growth factors may control tumor neurogenesis and may lead to new antineurogenic therapies for prostate cancer. © 2014 UICC.
Demonstration of Autonomous Rendezvous Technology (DART) Project Summary
NASA Technical Reports Server (NTRS)
Rumford, TImothy E.
2003-01-01
Since the 1960's, NASA has performed numerous rendezvous and docking missions. The common element of all US rendezvous and docking is that the spacecraft has always been piloted by astronauts. Only the Russian Space Program has developed and demonstrated an autonomous capability. The Demonstration of Autonomous Rendezvous Technology (DART) project currently funded under NASA's Space Launch Initiative (SLI) Cycle I, provides a key step in establishing an autonomous rendezvous capability for the United States. DART's objective is to demonstrate, in space, the hardware and software necessary for autonomous rendezvous. Orbital Sciences Corporation intends to integrate an Advanced Video Guidance Sensor and Autonomous Rendezvous and Proximity Operations algorithms into a Pegasus upper stage in order to demonstrate the capability to autonomously rendezvous with a target currently in orbit. The DART mission will occur in April 2004. The launch site will be Vandenburg AFB and the launch vehicle will be a Pegasus XL equipped with a Hydrazine Auxiliary Propulsion System 4th stage. All mission objectives will be completed within a 24 hour period. The paper provides a summary of mission objectives, mission overview and a discussion on the design features of the chase and target vehicles.
NASA Technical Reports Server (NTRS)
Fogel, L. J.; Calabrese, P. G.; Walsh, M. J.; Owens, A. J.
1982-01-01
Ways in which autonomous behavior of spacecraft can be extended to treat situations wherein a closed loop control by a human may not be appropriate or even possible are explored. Predictive models that minimize mean least squared error and arbitrary cost functions are discussed. A methodology for extracting cyclic components for an arbitrary environment with respect to usual and arbitrary criteria is developed. An approach to prediction and control based on evolutionary programming is outlined. A computer program capable of predicting time series is presented. A design of a control system for a robotic dense with partially unknown physical properties is presented.
New millennium program ST6: autonomous technologies for future NASA spacecraft
NASA Technical Reports Server (NTRS)
Chmielewski, Arthur B.; Chien, Steve; Sherwood, Robert; Wyman, William; Brady, T.; Buckley, S.; Tillier, C.
2005-01-01
The purpose of NASA's New Millennium Program (NMP) is to validate advanced technologies in space and thus lower the risk for the first mission user. The focus of NMP is only on those technologies which need space environment for proper validation. The ST6 project has developed two advanced, experimental technologies for use on spacecraft of the future. These technologies are the Autonomous Sciencecraft Experiment and the Inertial Stellar Compass. These technologies will improve spacecraft's ability to: make decisions on what information to gather and send back to the ground, determine its own attitude and adjust its pointing.
Simultaneous Planning and Control for Autonomous Ground Vehicles
2009-02-01
these applications is called A * ( A -star), and it was originally developed by Hart, Nilsson, and Raphael [HAR68]. Their research presented the formal...sequence, rather than a dynamic programming approach. A * search is a technique originally developed for Artificial Intelligence 43 applications ... developed at the Center for Intelligent Machines and Robotics, serves as a platform for the implementation and testing discussed. autonomous
Visualizing Decision-making Behaviours in Agent-based Autonomous Spacecraft
NASA Technical Reports Server (NTRS)
North, Steve; Hennessy, Joseph F. (Technical Monitor)
2003-01-01
The authors will report initial progress on the PIAudit project as a Research Resident Associate Program. The objective of this research is to prototype a tool for visualizing decision-making behaviours in autonomous spacecraft. This visualization will serve as an information source for human analysts. The current visualization prototype for PIAudit combines traditional Decision Trees with Weights of Evidence.
Space station automation study: Autonomous systems and assembly, volume 2
NASA Technical Reports Server (NTRS)
Bradford, K. Z.
1984-01-01
This final report, prepared by Martin Marietta Denver Aerospace, provides the technical results of their input to the Space Station Automation Study, the purpose of which is to develop informed technical guidance in the use of autonomous systems to implement space station functions, many of which can be programmed in advance and are well suited for automated systems.
Ramirez-Zamora, Adolfo; Smith, Heather; Youn, Youngwon; Durphy, Jennifer; Shin, Damian S; Pilitsis, Julie G
2016-07-15
There is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. To describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. We retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. Unilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. Stimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN. Copyright © 2016 Elsevier B.V. All rights reserved.
Optimized Autonomous Space - In-situ Sensorweb: A new Tool for Monitoring Restless Volcanoes
NASA Astrophysics Data System (ADS)
Lahusen, R. G.; Kedar, S.; Song, W.; Chien, S.; Shirazi, B.; Davies, A.; Tran, D.; Pieri, D.
2007-12-01
An interagency team of earth scientists, space scientists and computer scientists are collaborating to develop a real-time monitoring system optimized for rapid deployment at restless volcanoes. The primary goals of this Optimized Autonomous Space In-situ Sensorweb (OASIS) are: 1) integrate complementary space and in-situ (ground-based) elements into an interactive, autonomous sensorweb; 2) advance sensorweb power and communication resource management technology; and 3) enable scalability for seamless infusion of future space and in-situ assets into the sensorweb. A prototype system will be deployed on Mount St. Helens by December 2009. Each node will include GPS, seismic, infrasonic and lightning (for ash plume detection) sensors plus autonomous decision making capabilities and interaction with EO-1 multi-spectral satellite. This three year project is jointly funded by NASA AIST program and USGS Volcano Hazards Program. Work has begun with a rigorous multi-disciplinary discussion and resulted in a system requirements document aimed to guide the design of OASIS and future networks and to achieve the project's stated goals. In this presentation we will highlight the key OASIS system requirements, their rationale and the physical and technical challenges they pose. Preliminary design decisions will be presented.
How to make an autonomous robot as a partner with humans: design approach versus emergent approach.
Fujita, M
2007-01-15
In this paper, we discuss what factors are important to realize an autonomous robot as a partner with humans. We believe that it is important to interact with people without boring them, using verbal and non-verbal communication channels. We have already developed autonomous robots such as AIBO and QRIO, whose behaviours are manually programmed and designed. We realized, however, that this design approach has limitations; therefore we propose a new approach, intelligence dynamics, where interacting in a real-world environment using embodiment is considered very important. There are pioneering works related to this approach from brain science, cognitive science, robotics and artificial intelligence. We assert that it is important to study the emergence of entire sets of autonomous behaviours and present our approach towards this goal.
Wang, Chu-An; Drasin, David; Pham, Catherine; Jedlicka, Paul; Zaberezhnyy, Vadym; Guney, Michelle; Li, Howard; Nemenoff, Raphael; Costello, James C.; Tan, Aik-Choon; Ford, Heide L.
2014-01-01
Misexpression of developmental transcription factors occurs often in human cancers, where embryonic programs may be reinstated in a context that promotes or sustains malignant development. In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer. We found that Six2 promoted breast cancer metastasis by a novel mechanism involving both transcriptional and epigenetic regulation of E-cadherin. Downregulation of E-cadherin by Six2 was necessary for its ability to increase soft agar growth and in vivo metastasis in an immune competent mouse model of breast cancer. Mechanistic investigations showed that Six2 represses E-cadherin expression by upregulating Zeb2, in part through a microRNA-mediated mechanism, and by stimulating promoter methylation of the E-cadherin gene (Cdh1). Clinically, SIX2 expression correlated inversely with CDH1 expression in human breast cancer specimens, corroborating the disease relevance of their interaction. Our findings establish Six2 as a regulator of metastasis in human breast cancers and demonstrate an epigenetic function for SIX family transcription factors in metastatic progression through the regulation of E-cadherin. PMID:25348955
Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M
2012-10-01
It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Mudan, Satwinder; Kumar, Jayant; Mafalda, Neves C.; Kusano, Tomokazu; Reccia, Isabella; Zanallato, Artur; Dalgleish, Angus; Habib, Nagy
2017-01-01
Abstract Rationale: An isolated splenic metastasis is a rare phenomenon noted in advanced stage melanoma. We report the role of radiofrequency (RF) -based splenic-preserving splenectomy in a patient with a solitary splenic metastasis from advanced stage melanoma that was managed with checkpoint inhibitors. Patient concerns: We report a case of a 60-year-old man who presented with multiple lung metastases and a solitary splenic metastasis with advanced stage melanoma following excision of primary from his trunk 2.3 years back. Diagnosis: Considering the diagnosis of advanced stage melanoma with multiple lung metastases and a solitary splenic metastasis, and its ongoing progressive nature. This case was discussed in the tumour board meeting. Interventions: A decision was made to commence treatment with immunotherapy in the form of PD-1 inhibitor (programmed cell death 1 receptor) pembrolizumab. Follow-up restaging computer tomography (CT) scan of the abdomen and chest showed a significant reduction in the lung and chest wall lesions, but the splenic lesion remained unchanged. Given the lack of response to treatment in the splenic metastasis and the significant decrease in lung metastases, the multidisciplinary team decided that a partial splenectomy combined with continued immunotherapy treatment would be appropriate as the success of immunotherapy was imminent within the splenic preservation. Outcomes: The postoperative recovery was smooth and the patient was discharged from hospital on the sixth postoperative day with normal platelets and white blood cells. The histopathological analysis of the resected specimen showed a metastatic melanoma with negative margins. At 10-month follow-up after the splenic resection the patient had not experienced further tumour recurrences. Lessons: Spleen-preserving resection for an isolated, solitary splenic metastasis of melanoma is a feasible approach as it not only preserves the ongoing efficacy of checkpoint inhibitors by preserving the physiological T cell milieu, but the immunomodulation properties of RF can produce potentially additional therapeutic benefit. PMID:29245341
Mudan, Satvinder; Kumar, Jayant; Mafalda, Neves C; Kusano, Tomokazu; Reccia, Isabella; Zanallato, Artur; Dalgleish, Angus; Habib, Nagy
2017-12-01
An isolated splenic metastasis is a rare phenomenon noted in advanced stage melanoma. We report the role of radiofrequency (RF) -based splenic-preserving splenectomy in a patient with a solitary splenic metastasis from advanced stage melanoma that was managed with checkpoint inhibitors. We report a case of a 60-year-old man who presented with multiple lung metastases and a solitary splenic metastasis with advanced stage melanoma following excision of primary from his trunk 2.3 years back. Considering the diagnosis of advanced stage melanoma with multiple lung metastases and a solitary splenic metastasis, and its ongoing progressive nature. This case was discussed in the tumour board meeting. A decision was made to commence treatment with immunotherapy in the form of PD-1 inhibitor (programmed cell death 1 receptor) pembrolizumab. Follow-up restaging computer tomography (CT) scan of the abdomen and chest showed a significant reduction in the lung and chest wall lesions, but the splenic lesion remained unchanged. Given the lack of response to treatment in the splenic metastasis and the significant decrease in lung metastases, the multidisciplinary team decided that a partial splenectomy combined with continued immunotherapy treatment would be appropriate as the success of immunotherapy was imminent within the splenic preservation. The postoperative recovery was smooth and the patient was discharged from hospital on the sixth postoperative day with normal platelets and white blood cells. The histopathological analysis of the resected specimen showed a metastatic melanoma with negative margins.At 10-month follow-up after the splenic resection the patient had not experienced further tumour recurrences. Spleen-preserving resection for an isolated, solitary splenic metastasis of melanoma is a feasible approach as it not only preserves the ongoing efficacy of checkpoint inhibitors by preserving the physiological T cell milieu, but the immunomodulation properties of RF can produce potentially additional therapeutic benefit.
Community motivations to engage in conservation behavior to conserve the Sumatran orangutan.
Nilsson, Danielle; Gramotnev, Galina; Baxter, Greg; Butler, James R A; Wich, Serge A; McAlpine, Clive A
2016-08-01
Community-based conservation programs in developing countries are often based on the assumption that heteronomous motivation (e.g., extrinsic incentives such as economic rewards and pressure or coercion to act) will incite local communities to adopt conservation behaviors. However, this may not be as effective or sustainable as autonomous motivations (e.g., an intrinsic desire to act due to inherent enjoyment or self-identification with a behavior and through freedom of choice). We analyzed the comparative effectiveness of heteronomous versus autonomous approaches to community-based conservation programs through a case study of Sumatran orangutan (Pongo abelii) conservation in 3 villages in Indonesia. Each village had a different conservation program design. We surveyed people (n = 240) to determine their motivations for and behavior changes relative to orangutan and orangutan habitat (forest) protection. Heteronomous motivations (e.g., income from tourism) led to greater self-reporting of behavior change toward orangutan protection. However, they did not change self-reported behavior toward forest (i.e., orangutan habitat) protection. The most effective approach to creating self-reported behavior change throughout the community was a combination of autonomous and heteronomous motivations. Individuals who were heteronomously motivated to protect the orangutan were more likely to have changed attitudes than to have changed their self-reported behavior. These findings demonstrate that the current paradigm of motivating communities in developing countries to adopt conservation behaviors primarily through monetary incentives and rewards should consider integrating autonomous motivational techniques that promote the intrinsic values of conservation. Such a combination has a greater potential to achieve sustainable and cost-effective conservation outcomes. Our results highlight the importance of using in-depth sociopsychological analyses to inform the design and implementation of community-based conservation programs. © 2016 Society for Conservation Biology.
Targarona Soler, Eduardo Ma; Jover Navalon, Jose Ma; Gutierrez Saiz, Javier; Turrado Rodríguez, Víctor; Parrilla Paricio, Pascual
2015-03-01
Residents in our country have achieved a homogenous surgical training by following a structured residency program. This is due to the existence of specific training programs for each specialty. The current program, approved in 2007, has a detailed list of procedures that a surgeon should have performed in order to complete training. The aim of this study is to analyze the applicability of the program with regard to the number of procedures performed during the residency period. A data collection form was designed that included the list of procedures from the program of the specialty; it was sent in April 2014 to all hospitals with accredited residency programs. In September 2014 the forms were analysed, and a general descriptive study was performed; a subanalysis according to the resident's sex and Autonomous region was also performed. The number of procedures performed according to the number of residents in the different centers was also analyzed. The survey was sent to 117 hospitals with accredited programs, which included 190 resident places. A total of 91 hospitals responded (53%). The training offered adapts in general to the specialty program. The total number of procedures performed in the different sub-areas, in laparoscopic and emergency surgery is correct or above the number recommended by the program, with the exception of esophageal-gastric and hepatobiliary surgery. The sub-analysis according to Autonomous region did not show any significant differences in the total number of procedures, however, there were significant differences in endocrine surgery (P=.001) and breast surgery (P=.042). A total of 55% of residents are female, with no significant differences in distribution in Autonomous regions. However, female surgeons operate more than their male counterparts during the residency period (512±226 vs. 625±244; P<.01). The number of residents in the hospital correlates with the number of procedures performed; the residents with more procedures trained in hospitals where there were less residents (669±237 vs. 527±209; P=.004). The surgical activity performed by spanish surgeons is adequate to the specialty program, except in hepatobiliary and esophageal-gastric surgery. The distribution is homogeneous in the different autonomous regions, although there are differences that depend on the number and sex the of residents in each hospital. This information is essential to evaluate the quality of the specialty program and to design new training programs. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Bowman, Natalie M.; Kawai, Vivian; Gilman, Robert H.; Bocangel, Cesar; Galdos-Cardenas, Gerson; Cabrera, Lilia; Levy, Michael Z.; Cornejo del Carpio, Juan Geny; Delgado, Freddy; Rosenthal, Lauren; Pinedo-Cancino, Vivian V.; Steurer, Francis; Seitz, Amy E.; Maguire, James H.; Bern, Caryn
2011-01-01
Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20–30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections. PMID:21212207
NASA Technical Reports Server (NTRS)
Carsey, Frank; Behar, Alberto
2004-01-01
We have continued to develop a concept for use of autonomous rovers, originally developed for use in planetary exploration, in polar science on Earth; the concept was the subject of a workshop, and this report summarizes and extends that workshop. The workshop on Antarctic Autonomous Scientific Vehicles and Traverses met at the National Geographic Society on February 14 and 15, 2001 to discuss scientific objectives and benefits of the use of autonomous rovers. The participants enthusiastically viewed rovers as being uniquely valuable for such tasks as data taking on tedious or repetitive routes, traverses in polar night, difficult or hazardous routes, extremely remote regions, routes requiring only simple instrumentation, traverses that must be conducted at low speed, augments of manned traverses, and scientific procedures not compatible with human presence or combustion engines. The workshop has concluded that instrumented autonomous vehicles, of the type being developed for planetary exploration, have the potential to contribute significantly to the way science in conducted in Antarctica while also aiding planetary technology development, and engaging the public's interest. Specific objectives can be supported in understanding ice sheet mass balance, sea ice heat and momentum exchange, and surface air chemistry processes. In the interval since the workshop, we have concluded that organized program to employ such rovers to perform scientific tasks in the Fourth International Polar Year would serve the objectives of that program well.
Earth observations satellite data policy: Process and outcome
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shaffer, L.R.
1994-12-31
The National Aeronautics and Space Administration (NASA) develops, launches, and operates satellites to observe and monitor the Earth and its environment. This study categorizes each program based on the relationship between NASA and external organizations. A program can be an autonomous mission undertaken for NASA`s own constituency, or it can involve a client agency or a partner. These relationships affect how data policy decisions are made and implemented, and how the valuable output of NASA`s Earth observations satellites is managed. The process in NASA for determining which programs will be approved is very informal. Ideas and concepts surface and reachmore » the consciousness of NASA management; if sufficient support is achieved, a proposal can move to the feasibility study phase and from there become an approved and funded mission. The handling of data can be an important consideration in generating political support for program approval. Autonomous programs tend to have decisions made at lower levels and documented informally or not at all. Data policy is part of routine implementation of programs and does not generally rise to the visibility of the agency head or congressional staff or the Executive Office of the President. Responsibility for data management for autonomous missions is retained at NASA centers. Client programs involve higher level decision makers, and are the subject of political interest because they cross agency boundaries. The data policy process includes presidential statements on data access. As part of the client relationship, NASA often provides resources to the client for data handling and analysis, and shares these responsibilities. Data policy for partner programs is the result of bargaining between the partners, either foreign government agencies or private companies.« less
The EMT universe: space between cancer cell dissemination and metastasis initiation.
Ombrato, Luigi; Malanchi, Ilaria
2014-01-01
Tumor metastasis, the cause of more than 90% of cancer cell mortality, is a multistep process by which tumor cells disseminate from their primary site via local invasion and intravasation into blood or lymphatic vessels and reach secondary distant sites, where they survive and reinitiate tumor growth. Activation of a developmental program called the epithelial-to-mesenchymal transition (EMT) has been shown to be a very efficient strategy adopted by epithelial cancer cells to promote local invasion and dissemination at distant organs. Remarkably, the activation of EMT programs in epithelial cells correlates with the appearance of stemness. This finding suggests that the EMT process also drives the initial cancer cell colonization at distant sites. However, recent studies support the concept that its reverse program, a mesenchymal-to-epithelial transition, is required for efficient metastatic colonization and that EMT is not necessarily associated with stemness. This review analyzes the conflicting experimental evidence linking epithelial plasticity to stemness in the light of an "EMT gradient model," according to which the outcome of EMT program activation in epithelial cells would be bimodal: coupled to stemness during initial activation, but when forced to reach an advanced mesenchymal status, it would become incompatible with stem cell abilities.
Manifold traversing as a model for learning control of autonomous robots
NASA Technical Reports Server (NTRS)
Szakaly, Zoltan F.; Schenker, Paul S.
1992-01-01
This paper describes a recipe for the construction of control systems that support complex machines such as multi-limbed/multi-fingered robots. The robot has to execute a task under varying environmental conditions and it has to react reasonably when previously unknown conditions are encountered. Its behavior should be learned and/or trained as opposed to being programmed. The paper describes one possible method for organizing the data that the robot has learned by various means. This framework can accept useful operator input even if it does not fully specify what to do, and can combine knowledge from autonomous, operator assisted and programmed experiences.
NASA Technical Reports Server (NTRS)
Truong, Long V.; Walters, Jerry L.; Roth, Mary Ellen; Quinn, Todd M.; Krawczonek, Walter M.
1990-01-01
The goal of the Autonomous Power System (APS) program is to develop and apply intelligent problem solving and control to the Space Station Freedom Electrical Power System (SSF/EPS) testbed being developed and demonstrated at NASA Lewis Research Center. The objectives of the program are to establish artificial intelligence technology paths, to craft knowledge-based tools with advanced human-operator interfaces for power systems, and to interface and integrate knowledge-based systems with conventional controllers. The Autonomous Power EXpert (APEX) portion of the APS program will integrate a knowledge-based fault diagnostic system and a power resource planner-scheduler. Then APEX will interface on-line with the SSF/EPS testbed and its Power Management Controller (PMC). The key tasks include establishing knowledge bases for system diagnostics, fault detection and isolation analysis, on-line information accessing through PMC, enhanced data management, and multiple-level, object-oriented operator displays. The first prototype of the diagnostic expert system for fault detection and isolation has been developed. The knowledge bases and the rule-based model that were developed for the Power Distribution Control Unit subsystem of the SSF/EPS testbed are described. A corresponding troubleshooting technique is also described.
The development and flight test of a deployable precision landing system for spacecraft recovery
NASA Technical Reports Server (NTRS)
Sim, Alex G.; Murray, James E.; Neufeld, David C.; Reed, R. Dale
1993-01-01
A joint NASA Dryden Flight Research Facility and Johnson Space Center program was conducted to determine the feasibility of the autonomous recovery of a spacecraft using a ram-air parafoil system for the final stages of entry from space that included a precision landing. The feasibility of this system was studied using a flight model of a spacecraft in the generic shape of a flattened biconic which weighed approximately 150 lb and was flown under a commercially available, ram-air parachute. Key elements of the vehicle included the Global Positioning System guidance for navigation, flight control computer, ultrasonic sensing for terminal altitude, electronic compass, and onboard data recording. A flight test program was used to develop and refine the vehicle. This vehicle completed an autonomous flight from an altitude of 10,000 ft and a lateral offset of 1.7 miles which resulted in a precision flare and landing into the wind at a predetermined location. At times, the autonomous flight was conducted in the presence of winds approximately equal to vehicle airspeed. Several techniques for computing the winds postflight were evaluated. Future program objectives are also presented.
Evolution of Autonomous Self-Righting Behaviors for Articulated Nanorovers
NASA Technical Reports Server (NTRS)
Tunstel, Edward
1999-01-01
Miniature rovers with articulated mobility mechanisms are being developed for planetary surface exploration on Mars and small solar system bodies. These vehicles are designed to be capable of autonomous recovery from overturning during surface operations. This paper describes a computational means of developing motion behaviors that achieve the autonomous recovery function. It proposes a control software design approach aimed at reducing the effort involved in developing self-righting behaviors. The approach is based on the integration of evolutionary computing with a dynamics simulation environment for evolving and evaluating motion behaviors. The automated behavior design approach is outlined and its underlying genetic programming infrastructure is described.
NASA Technical Reports Server (NTRS)
Guo, Daniel
2017-01-01
The NASA Platform for Autonomous Systems (NPAS) toolkit is currently being used at the NASA John C. Stennis Space Center (SSC) to develop the INSIGHT program, which will autonomously monitor and control the Nitrogen System of the High Pressure Gas Facility (HPGF) on site. The INSIGHT program is in need of generic timing capabilities in order to perform timing based actions such as pump usage timing and sequence step timing. The purpose of this project was to develop a timing module that could fulfill these requirements and be adaptable for expanded use in the future. The code was written in Gensym G2 software platform, the same as INSIGHT, and was written generically to ensure compatibility with any G2 program. Currently, the module has two timing capabilities, a stopwatch function and a countdown function. Although the module has gone through some functionality testing, actual integration of the module into NPAS and the INSIGHT program is contingent on the module passing later checks.
NASA Technical Reports Server (NTRS)
Simmons, Reid; Apfelbaum, David
2005-01-01
Task Description Language (TDL) is an extension of the C++ programming language that enables programmers to quickly and easily write complex, concurrent computer programs for controlling real-time autonomous systems, including robots and spacecraft. TDL is based on earlier work (circa 1984 through 1989) on the Task Control Architecture (TCA). TDL provides syntactic support for hierarchical task-level control functions, including task decomposition, synchronization, execution monitoring, and exception handling. A Java-language-based compiler transforms TDL programs into pure C++ code that includes calls to a platform-independent task-control-management (TCM) library. TDL has been used to control and coordinate multiple heterogeneous robots in projects sponsored by NASA and the Defense Advanced Research Projects Agency (DARPA). It has also been used in Brazil to control an autonomous airship and in Canada to control a robotic manipulator.
Hyperfunctioning thyroid cancer: a five-year follow-up.
Azevedo, Monalisa Ferreira; Casulari, Luiz Augusto
2010-02-01
Differentiated thyroid cancer rarely occurs in association with hyperfunctioning nodules. We describe a case of a 47-year-old woman who developed symptoms of hyperthyroidism associated with a palpable thyroid nodule. Thyroid scintigraphy showed an autonomous nodule, and fine-needle aspiration biopsy was suggestive of papillary carcinoma. Laboratorial findings were consistent with the diagnosis of hyperthyroidism. The patient underwent thyroidectomy and a papillary carcinoma of 3.0 x 3.0 x 2.0 cm, follicular variant, was described by histological examination. The surrounding thyroid tissue was normal. Postoperatively, the patient received 100 mCi of (131)I, and whole body scans detected only residual uptake. No evidence of metastasis was detected during five years of follow-up. Hot thyroid nodules rarely harbor malignancies, and this case illustrated that, when a carcinoma occurs the prognosis seems to be very good with no evidence of metastatic dissemination during a long-term follow-up.
Automatically calibrating admittances in KATE's autonomous launch operations model
NASA Technical Reports Server (NTRS)
Morgan, Steve
1992-01-01
This report documents a 1000-line Symbolics LISP program that automatically calibrates all 15 fluid admittances in KATE's Autonomous Launch Operations (ALO) model. (KATE is Kennedy Space Center's Knowledge-based Autonomous Test Engineer, a diagnosis and repair expert system created for use on the Space Shuttle's various fluid flow systems.) As a new KATE application, the calibrator described here breaks new ground for KSC's Artificial Intelligence Lab by allowing KATE to both control and measure the hardware she supervises. By automating a formerly manual process, the calibrator: (1) saves the ALO model builder untold amounts of labor; (2) enables quick repairs after workmen accidently adjust ALO's hand valves; and (3) frees the modeler to pursue new KATE applications that previously were too complicated. Also reported are suggestions for enhancing the program: (1) to calibrate ALO's TV cameras, pumps, and sensor tolerances; and (2) to calibrate devices in other KATE models, such as the shuttle's LOX and Environment Control System (ECS).
Distributed Autonomous Control of Multiple Spacecraft During Close Proximity Operations
2007-12-01
programs may be the XSS-11. The AFRL Space Vehicle Directorate at Kirtland Air Force Base in New Mexico developed the XSS-11 in order to exhibit the...the LQR/APF algorithm appears to be a promising new development for the field of multiple spacecraft close proximity maneuver control. Monte...dissertation reports the development of an autonomous distributed control algorithm for multiple spacecraft during close proximity operations
Future Rear View Mirror: How We Learned to Love Lethal Autonomous Systems
2017-05-24
employment in the military and all other sectors. With a US-led consensus, the international community can solidify norms and standards for the most... ethical , moral, and legal employment of LAS in wartime and in peace. 15. SUBJECT TERMS killer robots, lethal autonomous systems, ethics , future...satisfaction of the requirements of the Ethics and Emerging Military Technology Certificate Program. The contents of this paper reflect my own
NASA Technical Reports Server (NTRS)
Ip, Felipe; Dohm, J. M.; Baker, V. R.; Castano, B.; Chien, S.; Cichy, B.; Davies, A. G.; Doggett, T.; Greeley, R.; Sherwood, R.
2005-01-01
NASA's New Millennium Program (NMP) Autonomous Sciencecraft Experiment (ASE) [1-3] has been successfully demonstrated in Earth-orbit. NASA has identified the development of an autonomously operating spacecraft as a necessity for an expanded program of missions exploring the Solar System. The versatile ASE spacecraft command and control, image formation, and science processing software was uploaded to the Earth Observer 1 (EO-1) spacecraft in early 2004 and has been undergoing onboard testing since May 2004 for the near real-time detection of surface modification related to transient geological and hydrological processes such as volcanism [4], ice formation and retreat [5], and flooding [6]. Space autonomy technology developed as part of ASE creates the new capability to autonomously detect, assess, react to, and monitor dynamic events such as flooding. Part of the challenge has been the difficulty to observe flooding in real time at sufficient temporal resolutions; more importantly, it is the large spatial extent of most drainage networks coupled with the size of the data sets necessary to be downlinked from satellites that make it difficult to monitor flooding from space. Below is a description of the algorithms (referred to as ASE Flood water Classifiers) used in tandem with the Hyperion spectrometer instrument on EO-1 to identify flooding and some of the test results.
Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.
Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio
2011-01-01
Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.
Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso
2014-08-01
Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.
NASA Technical Reports Server (NTRS)
Sterritt, Roy (Inventor); Hinchey, Michael G. (Inventor); Penn, Joaquin (Inventor)
2011-01-01
Systems, methods and apparatus are provided through which in some embodiments, an agent-oriented specification modeled with MaCMAS, is analyzed, flaws in the agent-oriented specification modeled with MaCMAS are corrected, and an implementation is derived from the corrected agent-oriented specification. Described herein are systems, method and apparatus that produce fully (mathematically) tractable development of agent-oriented specification(s) modeled with methodology fragment for analyzing complex multiagent systems (MaCMAS) and policies for autonomic systems from requirements through to code generation. The systems, method and apparatus described herein are illustrated through an example showing how user formulated policies can be translated into a formal mode which can then be converted to code. The requirements-based programming systems, method and apparatus described herein may provide faster, higher quality development and maintenance of autonomic systems based on user formulation of policies.
A Collaborative Knowledge Plane for Autonomic Networks
NASA Astrophysics Data System (ADS)
Mbaye, Maïssa; Krief, Francine
Autonomic networking aims to give network components self-managing capabilities. Several autonomic architectures have been proposed. Each of these architectures includes sort of a knowledge plane which is very important to mimic an autonomic behavior. Knowledge plane has a central role for self-functions by providing suitable knowledge to equipment and needs to learn new strategies for more accuracy.However, defining knowledge plane's architecture is still a challenge for researchers. Specially, defining the way cognitive supports interact each other in knowledge plane and implementing them. Decision making process depends on these interactions between reasoning and learning parts of knowledge plane. In this paper we propose a knowledge plane's architecture based on machine learning (inductive logic programming) paradigm and situated view to deal with distributed environment. This architecture is focused on two self-functions that include all other self-functions: self-adaptation and self-organization. Study cases are given and implemented.
Autonomous Cryogenic Load Operations: Knowledge-Based Autonomous Test Engineer
NASA Technical Reports Server (NTRS)
Schrading, J. Nicolas
2013-01-01
The Knowledge-Based Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20 years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in the system. As part of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display of the entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledge base, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.
Autonomous mobile robot research using the HERMIES-III robot
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pin, F.G.; Beckerman, M.; Spelt, P.F.
1989-01-01
This paper reports on the status and future directions in the research, development and experimental validation of intelligent control techniques for autonomous mobile robots using the HERMIES-III robot at the Center for Engineering Systems Advanced research (CESAR) at Oak Ridge National Laboratory (ORNL). HERMIES-III is the fourth robot in a series of increasingly more sophisticated and capable experimental test beds developed at CESAR. HERMIES-III is comprised of a battery powered, onmi-directional wheeled platform with a seven degree-of-freedom manipulator arm, video cameras, sonar range sensors, laser imaging scanner and a dual computer system containing up to 128 NCUBE nodes in hypercubemore » configuration. All electronics, sensors, computers, and communication equipment required for autonomous operation of HERMIES-III are located on board along with sufficient battery power for three to four hours of operation. The paper first provides a more detailed description of the HERMIES-III characteristics, focussing on the new areas of research and demonstration now possible at CESAR with this new test-bed. The initial experimental program is then described with emphasis placed on autonomous performance of human-scale tasks (e.g., valve manipulation, use of tools), integration of a dexterous manipulator and platform motion in geometrically complex environments, and effective use of multiple cooperating robots (HERMIES-IIB and HERMIES- III). The paper concludes with a discussion of the integration problems and safety considerations necessarily arising from the set-up of an experimental program involving human-scale, multi-autonomous mobile robots performance. 10 refs., 3 figs.« less
Autonomous Cryogenic Load Operations: KSC Autonomous Test Engineer
NASA Technical Reports Server (NTRS)
Shrading, Nicholas J.
2012-01-01
The KSC Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20+ years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in. the system, As part.of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display ofthe entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledgebase, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.
The Power of Peers in Employee Assistance: A Unique Program for a Community College.
ERIC Educational Resources Information Center
Hills, Marcia D.; And Others
1989-01-01
Describes the Red Deer College employee assistance program "Resources for Employee Assistance, Counselling and Health (REACH)" which has moved beyond this traditional approach to become an autonomous program run by employees for employees. Notes REACH is concerned with job performance and coping skills that contribute to individual and…
Reducing the Volume of NASA Earth-Science Data
NASA Technical Reports Server (NTRS)
Lee, Seungwon; Braverman, Amy J.; Guillaume, Alexandre
2010-01-01
A computer program reduces data generated by NASA Earth-science missions into representative clusters characterized by centroids and membership information, thereby reducing the large volume of data to a level more amenable to analysis. The program effects an autonomous data-reduction/clustering process to produce a representative distribution and joint relationships of the data, without assuming a specific type of distribution and relationship and without resorting to domain-specific knowledge about the data. The program implements a combination of a data-reduction algorithm known as the entropy-constrained vector quantization (ECVQ) and an optimization algorithm known as the differential evolution (DE). The combination of algorithms generates the Pareto front of clustering solutions that presents the compromise between the quality of the reduced data and the degree of reduction. Similar prior data-reduction computer programs utilize only a clustering algorithm, the parameters of which are tuned manually by users. In the present program, autonomous optimization of the parameters by means of the DE supplants the manual tuning of the parameters. Thus, the program determines the best set of clustering solutions without human intervention.
Autonomic adaptation after traditional and reverse swimming training periodizations.
Clemente-Suárez, Vicente Javier; Fernandes, R J; Arroyo-Toledo, J J; Figueiredo, P; González-Ravé, J M; Vilas-Boas, J P
2015-03-01
The objective of the present study was to analyze the autonomic response of trained swimmers to traditional and reverse training periodization models. Seventeen swimmers were divided in two groups, performing a traditional periodization (TPG) or a reverse periodization (RPG) during a period of 10 weeks. Heart rate variability and 50 m swimming performance were analyzed before and after the training programs. After training, the TPG decreased the values of the high frequency band (HF), the number of differences between adjacent normal R-R intervals longer than 50 ms (NN50) and the percentage of differences between adjacent normal R-R intervals more than 50 ms (pNN50), and the RPG increased the values of HF and square root of the mean of the sum of the squared differences between adjacent normal R-R intervals (RMSSD). None of the groups improved significantly their performance in the 50-m test. The autonomic response of swimmers was different depending on the periodization performed, with the reverse periodization model leading to higher autonomic adaption. Complementary, the data suggests that autonomic adaptations were not critical for the 50-m swimming performance.
van Empel, Pieter J; Verdam, Mathilde G E; Strypet, Magnus; van Rijssen, Lennart B; Huirne, Judith A; Scheele, Fedde; Bonjer, H Jaap; Meijerink, W Jeroen
2012-01-01
Knot tying and suturing skills in minimally invasive surgery (MIS) differ markedly from those in open surgery. Appropriate MIS training is mandatory before implementation into practice. The Advanced Suturing Course (ASC) is a structured simulator based training course that includes a 6-week autonomous training period at home on a traditional laparoscopic box trainer. Previous research did not demonstrate a significant progress in laparoscopic skills after this training period. This study aims to identify factors determining autonomous training on a laparoscopic box trainer at home. Residents (n = 97) attending 1 of 7 ASC courses between January 2009 and June 2011 were consecutively included. After 6 weeks of autonomous, training a questionnaire was completed. A random subgroup of 30 residents was requested to keep a time log. All residents received an online survey after attending the ASC. We performed outcome comparison to examine the accuracy of individual responses. Out of 97 residents, the main motives for noncompliant autonomous training included a lack of (training) time after working hours (n = 80, 83.3%), preferred practice time during working hours (n = 76, 31.6%), or another surgical interest than MIS (n = 79, 15.2%). Previously set training goals would encourage autonomous training according to 27.8% (n = 18) of residents. Thirty participants submitted a time log and reported an average 76.5-minute weekly training time. All residents confirmed that autonomous home practice on a laparoscopic box trainer is valuable. Autonomous practice should be structured and inclusive of adequate and sufficient feedback points. A minimally required practice time should be set. An obligatory assessment, including corresponding consequence should be conducted. Compliance herewith may result in increased voluntary (autonomous) simulator based (laparoscopic) training by residents. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.
CRUSER News. Issue 3, May 2011
2011-05-01
Program for Lagrangian Ocean Studies by Kanna Rajan, Principal Researcher for Autonomy, MBARI http://www.mbari.org/staff/ kanna / The Monterey Bay Aquarium...Ethical From Concept Generation to Experimentation INSIDE THIS ISSUE MBARI’S AUTONOMOUS SYSTEMS PROGRAM Kanna Rajan DIRECTOR’S CORNER CAPT (ret
Autonomous Science Analysis with the New Millennium Program-Autonomous Sciencecraft Experiment
NASA Astrophysics Data System (ADS)
Doggett, T.; Davies, A. G.; Castano, R. A.; Baker, V. R.; Dohm, J. M.; Greeley, R.; Williams, K. K.; Chien, S.; Sherwood, R.
2002-12-01
The NASA New Millennium Program (NMP) is a testbed for new, high-risk technologies, including new software and hardware. The Autonomous Sciencecraft Experiment (ASE) will fly on the Air Force Research Laboratory TechSat-21 mission in 2006 is such a NMP mission, and is managed by the Jet Propulsion Laboratory, California Institute of Technology. TechSat-21 consists of three satellites, each equipped with X-band Synthetic Aperture Radar (SAR) that will occupy a 13-day repeat track Earth orbit. The main science objectives of ASE are to demonstrate that process-related change detection and feature identification can be conducted autonomously during space flight, leading to autonomous onboard retargeting of the spacecraft. This mission will observe transient geological and environmental processes using SAR. Examples of geologic processes that may be observed and investigated include active volcanism, the movement of sand dunes and transient features in desert environments, water flooding, and the formation and break-up of lake ice. Science software onboard the spacecraft will allow autonomous processing and formation of SAR images and extraction of scientific information. The subsequent analyses, performed on images formed onboard from the SAR data, will include feature identification using scalable feature "templates" for each target, change detection through comparison of current and archived images, and science discovery, a search for other features of interest in each image. This approach results in obtaining the same science return for a reduced amount of resource use (such as downlink) when compared to that from a mission operating without ASE technology. Redundant data is discarded. The science-driven goals of ASE will evolve during the ASE mission through onboard replanning software that can re-task satellite operations. If necessary, as a result of a discovery made autonomously by onboard science processing, existing observation sequences will be pre-empted to obtain data of potential high scientific content. Flight validation of this software will enable radically different missions with significant onboard decision-making and novel science concepts (onboard decision making and selective data return). This work has been carried out at the Jet Propulsion Laboratory-California Institute of Technology, under contract to NASA.
Prevention and control of Hb Bart's disease in Guangxi Zhuang Autonomous Region, China.
He, Sheng; Zhang, Qiang; Li, Dongming; Chen, Shaoke; Tang, Yanqing; Chen, Qiuli; Zheng, Chenguang
2014-07-01
To demonstrate the performance of Hb Bart's Disease prevention in Guangxi Zhuang Autonomous Region, China. A prenatal control program for Hb Bart's disease was conducted from January 2006 to December 2012. A total of 17,555 pregnant women were screened for α-thalassemia in our prenatal screening program. Pregnancy at-risk for Hb Bart's disease was offered the choice of direct invasive testing or the non-invasive approach with serial ultrasonography. A total of 1425 at-risk couples attended the prenatal diagnosis. Three hundred ninety couples were screened at our own hospital, and the remaining 1035 couples were referred from other hospitals. Two hundred and three pregnant women chose non-invasive approach, and 1122 chose invasive testing. A total of 365 fetuses were diagnosed with Hb Bart's disease. All cases were finally confirmed by fetal DNA analysis. Eighty-two cases (22.4%) were diagnosed by chorionic villous sampling and 194 (53.2%) by amniocentesis samples. The other 89 (24.4%) cases were performed by cordocentesis. All of the affected pregnancies were terminated. Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in Guangxi Zhuang Autonomous Region, China. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Immobile Robots: AI in the New Millennium
NASA Technical Reports Server (NTRS)
Williams, Brian C.; Nayak, P. Pandurang
1996-01-01
A new generation of sensor rich, massively distributed, autonomous systems are being developed that have the potential for profound social, environmental, and economic change. These include networked building energy systems, autonomous space probes, chemical plant control systems, satellite constellations for remote ecosystem monitoring, power grids, biosphere-like life support systems, and reconfigurable traffic systems, to highlight but a few. To achieve high performance, these immobile robots (or immobots) will need to develop sophisticated regulatory and immune systems that accurately and robustly control their complex internal functions. To accomplish this, immobots will exploit a vast nervous system of sensors to model themselves and their environment on a grand scale. They will use these models to dramatically reconfigure themselves in order to survive decades of autonomous operations. Achieving these large scale modeling and configuration tasks will require a tight coupling between the higher level coordination function provided by symbolic reasoning, and the lower level autonomic processes of adaptive estimation and control. To be economically viable they will need to be programmable purely through high level compositional models. Self modeling and self configuration, coordinating autonomic functions through symbolic reasoning, and compositional, model-based programming are the three key elements of a model-based autonomous systems architecture that is taking us into the New Millennium.
Need satisfaction, motivational regulations and exercise: moderation and mediation effects.
Weman-Josefsson, Karin; Lindwall, Magnus; Ivarsson, Andreas
2015-05-20
Based on the Self-determination theory process model, this study aimed to explore relationships between the latent constructs of psychological need satisfaction, autonomous motivation and exercise behaviour; the mediational role of autonomous motivation in the association of psychological need satisfaction with exercise behaviour; as well as gender and age differences in the aforementioned associations. Adult active members of an Internet-based exercise program (n = 1091) between 18 and 78 years of age completed a test battery on motivational aspects based on Self-determination theory. The Basic Psychological Needs in Exercise Scale and the Behavioural Regulation in Exercise Questionnaire-2 were used to measure need satisfaction and type of motivation and the Leisure Time Exercise Questionnaire to measure self-reported exercise. Need satisfaction predicted autonomous motivation, which in turn predicted exercise, especially for women. Autonomous motivation was found to mediate the association between need satisfaction and exercise. Age and gender moderated several of the paths in the model linking need satisfaction with motivation and exercise. The results demonstrated gender and age differences in the proposed sequential mechanisms between autonomous motivation and exercise in the process model. This study thus highlights a potential value in considering moderating factors and the need to further examine the underlying mechanisms between needs, autonomous motivation, and exercise behaviour.
Supervised autonomous robotic soft tissue surgery.
Shademan, Azad; Decker, Ryan S; Opfermann, Justin D; Leonard, Simon; Krieger, Axel; Kim, Peter C W
2016-05-04
The current paradigm of robot-assisted surgeries (RASs) depends entirely on an individual surgeon's manual capability. Autonomous robotic surgery-removing the surgeon's hands-promises enhanced efficacy, safety, and improved access to optimized surgical techniques. Surgeries involving soft tissue have not been performed autonomously because of technological limitations, including lack of vision systems that can distinguish and track the target tissues in dynamic surgical environments and lack of intelligent algorithms that can execute complex surgical tasks. We demonstrate in vivo supervised autonomous soft tissue surgery in an open surgical setting, enabled by a plenoptic three-dimensional and near-infrared fluorescent (NIRF) imaging system and an autonomous suturing algorithm. Inspired by the best human surgical practices, a computer program generates a plan to complete complex surgical tasks on deformable soft tissue, such as suturing and intestinal anastomosis. We compared metrics of anastomosis-including the consistency of suturing informed by the average suture spacing, the pressure at which the anastomosis leaked, the number of mistakes that required removing the needle from the tissue, completion time, and lumen reduction in intestinal anastomoses-between our supervised autonomous system, manual laparoscopic surgery, and clinically used RAS approaches. Despite dynamic scene changes and tissue movement during surgery, we demonstrate that the outcome of supervised autonomous procedures is superior to surgery performed by expert surgeons and RAS techniques in ex vivo porcine tissues and in living pigs. These results demonstrate the potential for autonomous robots to improve the efficacy, consistency, functional outcome, and accessibility of surgical techniques. Copyright © 2016, American Association for the Advancement of Science.
Knowledge discovery for pancreatic cancer using inductive logic programming.
Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh
2014-08-01
Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.
2011-08-04
AND MULTI-BODY DYNAMICS Jayakumar , Smith, Ross, Jategaonkar, Konarzewski 4 August 2011 UNCLASSIFIED: Distribution Statement A. Approved for public...Autonomous Vehicle in an Off-Road Scenario Using Integrated Sensor, Controller, and Multi-Body Dynamics 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...Cannot neglect vehicle dynamics 4 August 2011 3 UNCLASSIFIED Importance of Simulation Fidelity • Performance evaluation requires entire system
Capek, Stepan; Krauss, William E; Amrami, Kimberly K; Parisi, Joseph E; Spinner, Robert J
2016-05-01
Perineural spread (PNS) is an unusual mechanism of tumor extension and has been typically reported in squamous cell carcinoma, adenocystic carcinoma, and desmoplastic melanoma. Our group has previously demonstrated PNS in rectal, prostate, bladder, and cervical cancer from the primary site along the autonomic nerves to the major somatic nerves and even intradurally. We believe similar principles apply to renal cell carcinoma (RCC) as well, despite the different anatomy. We performed a retrospective search to identify cases of intradural-extramedullary metastases of RCC caused by PNS. Strict anatomic and imaging inclusion criteria were defined: only lesions located between T6 and L3 were included, and PNS as a potential cause had to be supported by imaging evidence. Although 3 cases of spinal intradural metastases were identified, only one met our strict inclusion criteria. A 61-year-old woman developed a late intradural-extramedullary metastasis of RCC 16 years after the original diagnosis that we believe represents an example of visceral organ PNS. RCC can propagate via PNS from the primary tumor along the autonomic nerves to the aorticorenal, celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves to the corresponding spinal nerves and intradurally. We present radiologic evidence together with the review of the literature to support the premise that PNS of RCC not only occurs but goes unrecognized. Copyright © 2016 Elsevier Inc. All rights reserved.
Torchiaro, Erica; Lorenzato, Annalisa; Olivero, Martina; Valdembri, Donatella; Gagliardi, Paolo Armando; Gai, Marta; Erriquez, Jessica; Serini, Guido; Di Renzo, Maria Flavia
2016-01-05
The molecular mechanisms orchestrating peritoneal and hematogenous metastases of ovarian cancer cells are assumed to be distinct. We studied the p90RSK family of serine/threonine kinases that lie downstream the RAS-ERK/MAPK pathway and modulate a variety of cellular processes including cell proliferation, survival, motility and invasiveness. We found the RSK1 and RSK2 isoforms expressed in a number of human ovarian cancer cell lines, where they played redundant roles in sustaining in vitro motility and invasiveness. In vivo, silencing of both RSK1 and RSK2 almost abrogated short-term and long-term metastatic engraftment of ovarian cancer cells in the peritoneum. In addition, RSK1/RSK2 silenced cells failed to colonize the lungs after intravenous injection and to form hematogenous metastasis from subcutaneous xenografts. RSK1/RSK2 suppression resulted in lessened ovarian cancer cell spreading on endogenous fibronectin (FN). Mechanistically, RSK1/RSK2 knockdown diminished FN transcription, α5β1 integrin activation and TGF-β1 translation. Reduced endogenous FN deposition and TGF-β1 secretion depended on the lack of activating phosphorylation of the transcription/translation factor YB-1 by p90RSK. Altogether data show how p90RSK activates a self-reinforcing cell autonomous pro-adhesive circuit necessary for metastatic seeding of ovarian cancer cells. Thus, p90RSK inhibitors might hinder both the hematogenous and the peritoneal metastatic spread of human ovarian cancer.
Programming Enzyme-Initiated Autonomous DNAzyme Nanodevices in Living Cells.
Chen, Feng; Bai, Min; Cao, Ke; Zhao, Yue; Cao, Xiaowen; Wei, Jing; Wu, Na; Li, Jiang; Wang, Lihua; Fan, Chunhai; Zhao, Yongxi
2017-12-26
Molecular nanodevices are computational assemblers that switch defined states upon external stimulation. However, interfacing artificial nanodevices with natural molecular machineries in living cells remains a great challenge. Here, we delineate a generic method for programming assembly of enzyme-initiated DNAzyme nanodevices (DzNanos). Two programs including split assembly of two partzymes and toehold exchange displacement assembly of one intact DNAzyme initiated by telomerase are computed. The intact one obtains higher assembly yield and catalytic performance ascribed to proper conformation folding and active misplaced assembly. By employing MnO 2 nanosheets as both DNA carriers and source of Mn 2+ as DNAzyme cofactor, we find that this DzNano is well assembled via a series of conformational states in living cells and operates autonomously with sustained cleavage activity. Other enzymes can also induce corresponding DzNano assembly with defined programming modules. These DzNanos not only can monitor enzyme catalysis in situ but also will enable the implementation of cellular stages, behaviors, and pathways for basic science, diagnostic, and therapeutic applications as genetic circuits.
The Role of the Disabled in the Overall Picture of the Rehabilitation Process.
ERIC Educational Resources Information Center
Whitten, Cecil J.
In this experimental program the client is involved directly from the initial interview. The intention of the program is to give the disabled a more autonomous role by sharing common successes, problems and failures in group discussions with other disabled persons. Budgeting, child care, and nutrition are included in the academic program which…
The Languages of the Valencian Educational System: The Results of Two Decades of Language Policy.
ERIC Educational Resources Information Center
Arroyo, Jose Luis Blas
2002-01-01
The compulsory education system in the autonomous Spanish region known as the Comunidad Valenciano has offered a varied program of bilingual education. Spanish and Valenciano, an autochthonous variety of Catalan, alternate according to various curricular programs as the main teaching languages. Examines the objectives of each of these programs, as…
Mendes, Renata Gonçalves; Simões, Rodrigo Polaquini; Costa, Fernando de Souza Melo; Pantoni, Camila Bianca Falasco; Di Thommazo-Luporini, Luciana; Luzzi, Sérgio; Amaral-Neto, Othon; Arena, Ross; Catai, Aparecida Maria; Borghi-Silva, Audrey
2014-01-01
To assess whether the same exercise-based inpatient program applied to patients with normal and reduced left ventricular function (LVF) evokes a similar cardiac autonomic response after coronary artery bypass graft (CABG). Forty-four patients post-CABG, subgrouped according to normal LVF [LVFN: n = 23; left ventricular ejection fraction (LVEF) ≥ 55%] and reduced LVF (LVFR: n = 21; LVEF 35-54%), were included. All initiated the exercise protocol on post-operative day 1 (PO1), following a whole progressive program until discharge. Cardiac autonomic response was assessed by the indices of heart rate variability (HRV) at rest and during exercise (extremity range of motion and ambulation). During ambulation, lower values of HRV indices were found in the LVFR group compared with the LVFN group [standard deviation of all RR (STDRR; 6.1 ± 2.7 versus 8.9 ± 4.7 ms), baseline width of the RR histogram (TINN; 30.6 ± 14.8 versus 45.8 ± 24.9 ms), SD2 (14.8 ± 8.0 versus 21.3 ± 9.0 ms), Shannon entropy (3.6 ± 0.5 versus 3.9 ± 0.4) and correlation dimension (0.08 ± 0.2 versus 0.2 ± 0.2)]. Also, when comparing the ambulation to rest change, lower values were observed in the LVFR group for linear (STDRR, TINN, RR TRI, rMSSD) and non-linear (SD2 and correlation dimension) HRV indices (p < 0.05). On PO1, we observed only intra-group differences between rest and exercise (extremity range of motion), for mean intervals between heart beats and heart rate. For patients with LVFN, the same inpatient exercise protocol triggered a more attenuated autonomic response compared with patients with LVFR. These findings have implications as to how exercise should be prescribed according to LVF in the early stages following recovery from CABG. Implications for Rehabilitation Exercise-based inpatient program, performed by post-CABG patients who have normal left ventricular function, triggered a more attenuated cardiac autonomic response compared with patients with reduced left ventricular function. Volume of the inpatient exercises should be prescribed according to the left ventricular function in the early stages following recovery from CABG.
The MAP Autonomous Mission Control System
NASA Technical Reports Server (NTRS)
Breed, Juile; Coyle, Steven; Blahut, Kevin; Dent, Carolyn; Shendock, Robert; Rowe, Roger
2000-01-01
The Microwave Anisotropy Probe (MAP) mission is the second mission in NASA's Office of Space Science low-cost, Medium-class Explorers (MIDEX) program. The Explorers Program is designed to accomplish frequent, low cost, high quality space science investigations utilizing innovative, streamlined, efficient management, design and operations approaches. The MAP spacecraft will produce an accurate full-sky map of the cosmic microwave background temperature fluctuations with high sensitivity and angular resolution. The MAP spacecraft is planned for launch in early 2001, and will be staffed by only single-shift operations. During the rest of the time the spacecraft must be operated autonomously, with personnel available only on an on-call basis. Four (4) innovations will work cooperatively to enable a significant reduction in operations costs for the MAP spacecraft. First, the use of a common ground system for Spacecraft Integration and Test (I&T) as well as Operations. Second, the use of Finite State Modeling for intelligent autonomy. Third, the integration of a graphical planning engine to drive the autonomous systems without an intermediate manual step. And fourth, the ability for distributed operations via Web and pager access.
Principles of Queued Service Observing at CFHT
NASA Astrophysics Data System (ADS)
Manset, Nadine; Burdullis, T.; Devost, D.
2011-03-01
CFHT started to use Queued Service Observing in 2001, and is now operating in that mode over 95% of the time. Ten years later, the observations are now carried out by Remote Observers who are not present at the telescope (see the companion presentation "Remote Queued Service Observing at CFHT"). The next phase at CFHT will likley involve assisted or autonomous service observing (see the presentation "Artificial Intelligence in Autonomous Telescopes"), which would not be possible without first having a Queued observations system already in place. The advantages and disadvantages of QSO at CFHT will be reviewed. The principles of QSO at CFHT, which allow CFHT to complete 90-100% of the top 30-40% programs and often up to 80% of other accepted programs, will be presented, along with the strategic use of overfill programs, the method of agency balance, and the suite of planning, scheduling, analysis and data quality assessment tools available to Queue Coordinators and Remote Observers.
Autonomous satellite command and control: A comparison with other military systems
NASA Technical Reports Server (NTRS)
Kruchten, Robert J.; Todd, Wayne
1988-01-01
Existing satellite concepts of operation depend on readily available experts and are extremely manpower intensive. Areas of expertise required include mission planning, mission data interpretation, telemetry monitoring, and anomaly resolution. The concepts of operation have envolved to their current state in part because space systems have tended to be treated more as research and development assets rather than as operational assets. These methods of satellite command and control will be inadequate in the future because of the availability, survivability, and capability of human experts. Because space systems have extremely high reliability and limited access, they offer challenges not found in other military systems. Thus, automation techniques used elsewhere are not necessarily applicable to space systems. A program to make satellites much more autonomous has been developed, using a variety of advanced software techniques. The problem the program is addressing, some possible solutions, the goals of the Rome Air Development Center (RADC) program, the rationale as to why the goals are reasonable, and the current program status are discussed. Also presented are some of the concepts used in the program and how they differ from more traditional approaches.
Schneider, Sven; Kadletz, Lorenz; Wiebringhaus, Robert; Kenner, Lukas; Selzer, Edgar; Füreder, Thorsten; Rajky, Orsolya; Berghoff, Anna S; Preusser, Matthias; Heiduschka, Gregor
2018-05-09
Expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and impact on patients' clinical outcome. Immunohistochemical staining patterns of PD-L1 and PD-1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated to patients' clinical data. PD-L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis and significantly correlates with decreased overall survival (OS) (p=0.01) and disease free survival (DFS) (p=0.001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with presence of lymph node metastasis (p=0.0223). Infiltration of PD-1 expressing lymphocytes significantly correlates with favorable OS (p=0.001) and DFS (p=0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (p=0.007) and DFS (p=0.001). Presence of PD-1 TILs significantly correlates with better OS (p=0.005) and DFS (p=0) also in the HPV negative cohort. Cox regression multivariate analysis revealed PD-1 TIL expression as an independent prognostic marker for OS (p=0.004) and DFS (p=0.001) and T stage was validated as negative prognostic marker for OS (p=0.011). PD-1 expressing lymphocytes (p=0.0412) and PD-L1 expression (p=0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases. Our results characterize the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Lowney, J K; Frisella, M M; Lairmore, T C; Doherty, G M
1998-12-01
Islet cell tumor (ICT) metastasis is one of the potentially lethal outcomes of multiple endocrine neoplasia type 1 (MEN 1). Management of ICT in patients with MEN 1 is controversial; some advocate resection based on biochemical evidence of progression, whereas others use tumor size to predict the risk of metastasis and the need for resection. This study correlates the size of primary ICT with the presence of metastases. Forty-eight patients with MEN 1 with ICT, from 34 kindreds followed up in our multiple endocrine neoplasia program, were evaluated; 43 of the 48 have been explored for ICT. Metastases to the lymph nodes and liver were documented. Thirty-three percent of patients with pancreatic tumors less than 1 cm in greatest diameter had metastatic disease at surgery and in follow-up, whereas 34.8% of patients with tumors greater than 2 cm in diameter had metastases to lymph nodes or liver. The 2 patients with liver metastases each had primary tumors greater than 2 cm. Follow-up revealed subsequent metastasis in 1 patient. The size of primary tumors in MEN 1 does not correlate with metastatic potential. This is not a good criterion for exploration. Continued follow-up of these patients will be necessary to define the effect of operation on the course of ICT in MEN 1.
Orbital Express Mission Operations Planning and Resource Management using ASPEN
NASA Technical Reports Server (NTRS)
Chouinard, Caroline; Knight, Russell; Jones, Grailing; Tran, Danny
2008-01-01
The Orbital Express satellite servicing demonstrator program is a DARPA program aimed at developing "a safe and cost-effective approach to autonomously service satellites in orbit". The system consists of: a) the Autonomous Space Transport Robotic Operations (ASTRO) vehicle, under development by Boeing Integrated Defense Systems, and b) a prototype modular next-generation serviceable satellite, NEXTSat, being developed by Ball Aerospace. Flexibility of ASPEN: a) Accommodate changes to procedures; b) Accommodate changes to daily losses and gains; c) Responsive re-planning; and d) Critical to success of mission planning Auto-Generation of activity models: a) Created plans quickly; b) Repetition/Re-use of models each day; and c) Guarantees the AML syntax. One SRP per day vs. Tactical team
NASA Astrophysics Data System (ADS)
Croft, John; Deily, John; Hartman, Kathy; Weidow, David
1998-01-01
In the twenty-first century, NASA envisions frequent low-cost missions to explore the solar system, observe the universe, and study our planet. To realize NASA's goal, the Guidance, Navigation, and Control Center (GNCC) at the Goddard Space Flight Center sponsors technology programs that enhance spacecraft performance, streamline processes and ultimately enable cheaper science. Our technology programs encompass control system architectures, sensor and actuator components, electronic systems, design and development of algorithms, embedded systems and space vehicle autonomy. Through collaboration with government, universities, non-profit organizations, and industry, the GNCC incrementally develops key technologies that conquer NASA's challenges. This paper presents an overview of several innovative technology initiatives for the autonomous guidance, navigation, and control (GN&C) of satellites.
2012-10-01
asymptomatic. There are reports of silent AD during voiding7, bowel programs 8, sperm retrieval9, and possibly accupunture10. It is unclear what long...no recent similar episodes but holds a past history of AD associated headache during voiding while dealing with renal stone disease with 1-2...autonomic dysreflexia and silent autonomic dysreflexia in men with SCI undergoing sperm retrieval: Implications for clinical practice. J Spinal
SSTAC/ARTS review of the draft Integrated Technology Plan (ITP). Volume 6: Controls and guidance
NASA Technical Reports Server (NTRS)
1991-01-01
Viewgraphs of briefings from the Space Systems and Technology Advisory Committee (SSTAC)/ARTS review of the draft Integrated Technology Plan (ITP) on controls and guidance are included. Topics covered include: strategic avionics technology planning and bridging programs; avionics technology plan; vehicle health management; spacecraft guidance research; autonomous rendezvous and docking; autonomous landing; computational control; fiberoptic rotation sensors; precision instrument and telescope pointing; microsensors and microinstruments; micro guidance and control initiative; and earth-orbiting platforms controls-structures interaction.
2013-05-01
saliency, natural scene statistics 1. INTRODUCTION Research into the area of autonomous navigation for unmanned ground vehicles (UGV) has accelerated in...recent years. This is partly due to the success of programs such as the DARPA Grand Challenge1 and the dream of driverless cars ,2 but is also due to the...NOTES 14. ABSTRACT There have been several major advances in autonomous navigation for unmanned ground vehicles in controlled urban environments in
Solar Thermal Utility-Scale Joint Venture Program (USJVP) Final Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
MANCINI,THOMAS R.
2001-04-01
Several years ago Sandia National Laboratories developed a prototype interior robot [1] that could navigate autonomously inside a large complex building to aid and test interior intrusion detection systems. Recently the Department of Energy Office of Safeguards and Security has supported the development of a vehicle that will perform limited security functions autonomously in a structured exterior environment. The goal of the first phase of this project was to demonstrate the feasibility of an exterior robotic vehicle for security applications by using converted interior robot technology, if applicable. An existing teleoperational test bed vehicle with remote driving controls was modifiedmore » and integrated with a newly developed command driving station and navigation system hardware and software to form the Robotic Security Vehicle (RSV) system. The RSV, also called the Sandia Mobile Autonomous Navigator (SANDMAN), has been successfully used to demonstrate that teleoperated security vehicles which can perform limited autonomous functions are viable and have the potential to decrease security manpower requirements and improve system capabilities.« less
NASA's Autonomous Formation Flying Technology Demonstration, Earth Observing-1(EO-1)
NASA Technical Reports Server (NTRS)
Folta, David; Bristow, John; Hawkins, Albin; Dell, Greg
2002-01-01
NASA's first autonomous formation flying mission, the New Millennium Program's (NMP) Earth Observing-1 (EO-1) spacecraft, recently completed its principal goal of demonstrating advanced formation control technology. This paper provides an overview of the evolution of an onboard system that was developed originally as a ground mission planning and operations tool. We discuss the Goddard Space Flight Center s formation flying algorithm, the onboard flight design and its implementation, the interface and functionality of the onboard system, and the implementation of a Kalman filter based GPS data smoother. A number of safeguards that allow the incremental phasing in of autonomy and alleviate the potential for mission-impacting anomalies from the on- board autonomous system are discussed. A comparison of the maneuvers planned onboard using the EO-1 autonomous control system to those from the operational ground-based maneuver planning system is presented to quantify our success. The maneuvers discussed encompass reactionary and routine formation maintenance. Definitive orbital data is presented that verifies all formation flying requirements.
A Test-Bed Configuration: Toward an Autonomous System
NASA Astrophysics Data System (ADS)
Ocaña, F.; Castillo, M.; Uranga, E.; Ponz, J. D.; TBT Consortium
2015-09-01
In the context of the Space Situational Awareness (SSA) program of ESA, it is foreseen to deploy several large robotic telescopes in remote locations to provide surveillance and tracking services for man-made as well as natural near-Earth objects (NEOs). The present project, termed Telescope Test Bed (TBT) is being developed under ESA's General Studies and Technology Programme, and shall implement a test-bed for the validation of an autonomous optical observing system in a realistic scenario, consisting of two telescopes located in Spain and Australia, to collect representative test data for precursor NEO services. In order to fulfill all the security requirements for the TBT project, the use of a autonomous emergency system (AES) is foreseen to monitor the control system. The AES will monitor remotely the health of the observing system and the internal and external environment. It will incorporate both autonomous and interactive actuators to force the protection of the system (i.e., emergency dome close out).
Control technique for planetary rover
NASA Technical Reports Server (NTRS)
Nakatani, Ichiro; Kubota, Takashi; Adachi, Tadashi; Saitou, Hiroaki; Okamoto, Sinya
1994-01-01
Beginning next century, several schemes for sending a planetary rover to the moon or Mars are being planned. As part of the development program, autonomous navigation technology is being studied to allow the rover the ability to move autonomously over a long range of unknown planetary surface. In the previous study, we ran the autonomous navigation experiment on an outdoor test terrain by using a rover test-bed that was controlled by a conventional sense-plan-act method. In some cases during the experiment, a problem occurred with the rover moving into untraversable areas. To improve this situation, a new control technique has been developed that gives the rover the ability of reacting to the outputs of the proximity sensors, a reaction behavior if you will. We have developed a new rover test-bed system on which an autonomous navigation experiment was performed using the newly developed control technique. In this outdoor experiment, the new control technique effectively produced the control command for the rover to avoid obstacles and be guided to the goal point safely.
LABRADOR: a learning autonomous behavior-based robot for adaptive detection and object retrieval
NASA Astrophysics Data System (ADS)
Yamauchi, Brian; Moseley, Mark; Brookshire, Jonathan
2013-01-01
As part of the TARDEC-funded CANINE (Cooperative Autonomous Navigation in a Networked Environment) Program, iRobot developed LABRADOR (Learning Autonomous Behavior-based Robot for Adaptive Detection and Object Retrieval). LABRADOR was based on the rugged, man-portable, iRobot PackBot unmanned ground vehicle (UGV) equipped with an explosives ordnance disposal (EOD) manipulator arm and a custom gripper. For LABRADOR, we developed a vision-based object learning and recognition system that combined a TLD (track-learn-detect) filter based on object shape features with a color-histogram-based object detector. Our vision system was able to learn in real-time to recognize objects presented to the robot. We also implemented a waypoint navigation system based on fused GPS, IMU (inertial measurement unit), and odometry data. We used this navigation capability to implement autonomous behaviors capable of searching a specified area using a variety of robust coverage strategies - including outward spiral, random bounce, random waypoint, and perimeter following behaviors. While the full system was not integrated in time to compete in the CANINE competition event, we developed useful perception, navigation, and behavior capabilities that may be applied to future autonomous robot systems.
Monitoring fetal maturation—objectives, techniques and indices of autonomic function*
Hoyer, Dirk; Żebrowski, Jan; Cysarz, Dirk; Gonçalves, Hernâni; Pytlik, Adelina; Amorim-Costa, Célia; Bernardes, João; Ayres-de-Campos, Diogo; Witte, Otto W; Schleußner, Ekkehard; Stroux, Lisa; Redman, Christopher; Georgieva, Antoniya; Payne, Stephen; Clifford, Gari; Signorini, Maria G; Magenes, Giovanni; Andreotti, Fernando; Malberg, Hagen; Zaunseder, Sebastian; Lakhno, Igor; Schneider, Uwe
2017-01-01
Objective Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of ‘fetal programming’, also known as ‘developmental origins of adult disease hypothesis’, e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. Approach The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is key to fetal autonomic assessment. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Main Results Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) evaluation of fetal electrocardiographic (ECG) recordings, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. Significance The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies (CTG, handheld Doppler, MCG, ECG). The ultimate objective is their dissemination into routine practice and studies of fetal developmental disturbances with implications for programming of adult diseases. PMID:28186000
The Departmentalization of the ESL Program.
ERIC Educational Resources Information Center
Bolton, John K.
A review of prevailing patterns of sponsorship of college and university English as a second language (ESL) programs indicates that in community colleges, they tend to be housed in English departments. In four-year institutions they are generally in semi-autonomous units or institutes. The argument for departmental sponsorship is based on data…
Expert System Detects Power-Distribution Faults
NASA Technical Reports Server (NTRS)
Walters, Jerry L.; Quinn, Todd M.
1994-01-01
Autonomous Power Expert (APEX) computer program is prototype expert-system program detecting faults in electrical-power-distribution system. Assists human operators in diagnosing faults and deciding what adjustments or repairs needed for immediate recovery from faults or for maintenance to correct initially nonthreatening conditions that could develop into faults. Written in Lisp.
Robots as Language Learning Tools
ERIC Educational Resources Information Center
Collado, Ericka
2017-01-01
Robots are machines that resemble different forms, usually those of humans or animals, that can perform preprogrammed or autonomous tasks (Robot, n.d.). With the emergence of STEM programs, there has been a rise in the use of robots in educational settings. STEM programs are those where students study science, technology, engineering and…
Development of "Remotely Operated Vehicles for Education and Research" (ROVERs)
NASA Astrophysics Data System (ADS)
Gaines, J. E.; Bland, G.; Bydlowski, D.
2017-12-01
The University of South Florida is a team member for the AREN project which develops educational technologies for data acquisition. "Remotely Operated Vehicles for Education and Research" (ROVERs) are floatable data acquisition systems used for Earth science measurements. The USF partnership was productive in the first year, resulting in new autonomous ROVER platforms being developed and used during a 5 week STEM summer camp by middle school youth. ROVERs were outfitted with GPS and temperature sensors and programmed to move forward, backwards, and to turn autonomously using the National Instruments myRIO embedded system. GLOBE protocols were used to collect data. The outreach program's structure lended itself to accomplishing an essential development effort for the AREN project towards the use of the ROVER platform in informal educational settings. A primary objective of the partnership is curriculum development to integrate GLOBE protocols and NASA technology and hardware/ROVER development wher new ROVER platforms are explored. The USF partnership resulted in two design prototypes for ROVERs, both of which can be created from recyclable materials for flotation and either 3D printed or laser cut components. In addition, both use the National Instruments myRIO for autonomous control. We will present two prototypes designed for use during the USF outreach program, the structure of the program, and details on the fabrication of prototype Z during the program by middle school students. Considering the 5-year objective of the AREN project is to "develop approaches, learning plans, and specific tools that can be affordably implemented nationwide (globally)", the USF partnership is key as it contributes to each part of the objective in a unique and impactful way.
Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.
Röhling, Martin; Strom, Alexander; Bönhof, Gidon J; Roden, Michael; Ziegler, Dan
2017-10-23
This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.
Autonomous multifunctional nanobrushes-autonomous materials
NASA Astrophysics Data System (ADS)
Ghasemi-Nejhad, Mehrdad N.; Tius, Marcus A.
2007-04-01
In this work, taking advantage of carbon nanotubes' small size, and exceptional mechanical, chemical and electrical properties, we report on a series of nano-synthesis procedures that combine conventional chemical vapor deposition and selective substrate area growth followed by chemical functionalizations to fabricate functionalized nano-brushes from aligned carbon nanotube arrays and chemically selective functional groups. The high aspect ratio and small dimension, mechanical stability and flexibility, surface chemical and adhesive characteristics of carbon nanotubes provide opportunities to create nano-brushes with selected chemical functionalities. The nano-brushes are made from aligned multi-walled carbon nanotube bristles grafted onto long SiC fiber handles in various configurations and functionalized with various chemical functional groups. These nano-brushes can easily be manipulated physically, either manually or with the aid of motors. Here, we explain the autonomous characteristics of the functionalized nano-brushes employing functional chemical groups such that the nano-brush can potentially collect various metal particles, ions, and contaminants from liquid solutions and the air environment, autonomously. These functionalized multiwalled carbon nanotube based nano-brushes can work swiftly in both liquid and air environments. With surface modification and functionalization, the nanotube nano-brushes can potentially become a versatile nano-devices in many chemical and biological applications, where they can autonomously pick up the particles they encounter since they can be chemically programmed to function as Autonomous Chemical Nano Robots (ACNR).
Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.
Zhang, Min; Sun, Jimei
2013-12-01
To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.
Issues in the design of an executive controller shell for Space Station automation
NASA Technical Reports Server (NTRS)
Erickson, William K.; Cheeseman, Peter C.
1986-01-01
A major goal of NASA's Systems Autonomy Demonstration Project is to focus research in artificial intelligence, human factors, and dynamic control systems in support of Space Station automation. Another goal is to demonstrate the use of these technologies in real space systems, for both round-based mission support and on-board operations. The design, construction, and evaluation of an intelligent autonomous system shell is recognized as an important part of the Systems Autonomy research program. His paper describes autonomous systems and executive controllers, outlines how these intelligent systems can be utilized within the Space Station, and discusses a number of key design issues that have been raised during some preliminary work to develop an autonomous executive controller shell at NASA Ames Research Center.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kisholoy Goswami
2005-10-11
The goal of this project is to construct a prototype carbon dioxide sensor that can be commercialized to offer a low-cost, autonomous instrument for long-term, unattended measurements. Currently, a cost-effective CO2 sensor system is not available that can perform cross-platform measurements (ground-based or airborne platforms such as balloon and unmanned aerial vehicle (UAV)) for understanding the carbon sequestration phenomenon. The CO2 sensor would support the research objectives of DOE-sponsored programs such as AmeriFlux and the North American Carbon Program (NACP). Global energy consumption is projected to rise 60% over the next 20 years and use of oil is projected tomore » increase by approximately 40%. The combustion of coal, oil, and natural gas has increased carbon emissions globally from 1.6 billion tons in 1950 to 6.3 billion tons in 2000. This figure is expected to reach 10 billon tons by 2020. It is important to understand the fate of this excess CO2 in the global carbon cycle. The overall goal of the project is to develop an accurate and reliable optical sensor for monitoring carbon dioxide autonomously at least for one year at a point remote from the actual CO2 release site. In Phase I of this project, InnoSense LLC (ISL) demonstrated the feasibility of an ormosil-monolith based Autonomous Sensor for Atmospheric CO2 (ASAC) device. All of the Phase I objectives were successfully met.« less
Cutaneous metastasis of cholangiocarcinoma.
Liu, Min; Liu, Bai-Long; Liu, Bin; Guo, Liang; Wang, Qiang; Song, Yan-Qiu; Dong, Li-Hua
2015-03-14
To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.
Experiments in teleoperator and autonomous control of space robotic vehicles
NASA Technical Reports Server (NTRS)
Alexander, Harold L.
1991-01-01
A program of research embracing teleoperator and automatic navigational control of freely flying satellite robots is presented. Current research goals include: (1) developing visual operator interfaces for improved vehicle teleoperation; (2) determining the effects of different visual interface system designs on operator performance; and (3) achieving autonomous vision-based vehicle navigation and control. This research program combines virtual-environment teleoperation studies and neutral-buoyancy experiments using a space-robot simulator vehicle currently under development. Visual-interface design options under investigation include monoscopic versus stereoscopic displays and cameras, helmet-mounted versus panel-mounted display monitors, head-tracking versus fixed or manually steerable remote cameras, and the provision of vehicle-fixed visual cues, or markers, in the remote scene for improved sensing of vehicle position, orientation, and motion.
Deep Space 1: Testing New Technologies for Future Small Bodies Missions
NASA Technical Reports Server (NTRS)
Rayman, Marc D.
2001-01-01
Launched on October 24, 1998, Deep Space 1 (DS1) was the first mission of NASA's New Millennium Program, chartered to validate in space high-risk, new technologies important for future space science programs. The advanced technology payload that was tested on DS1 comprises solar electric propulsion, solar concentrator arrays, autonomous on-board navigation and other autonomous systems, several telecommunications and microelectronics devices, and two low-mass integrated science instrument packages. The mission met or exceeded all of its success criteria. The 12 technologies were rigorously exercised so that subsequent flight projects would not have to incur the cost and risk of being the fist users of these new capabilities. Examples of the benefits to future small body missions from DS1's technologies will be described.
The flight telerobotic servicer and technology transfer
NASA Technical Reports Server (NTRS)
Andary, James F.; Bradford, Kayland Z.
1991-01-01
The Flight Telerobotic Servicer (FTS) project at the Goddard Space Flight Center is developing an advanced telerobotic system to assist in and reduce crew extravehicular activity (EVA) for Space Station Freedom (SSF). The FTS will provide a telerobotic capability in the early phases of the SSF program and will be employed for assembly, maintenance, and inspection applications. The current state of space technology and the general nature of the FTS tasks dictate that the FTS be designed with sophisticated teleoperational capabilities for its internal primary operating mode. However, technologies such as advanced computer vision and autonomous planning techniques would greatly enhance the FTS capabilities to perform autonomously in less structured work environments. Another objective of the FTS program is to accelerate technology transfer from research to U.S. industry.
Ground vehicle control at NIST: From teleoperation to autonomy
NASA Technical Reports Server (NTRS)
Murphy, Karl N.; Juberts, Maris; Legowik, Steven A.; Nashman, Marilyn; Schneiderman, Henry; Scott, Harry A.; Szabo, Sandor
1994-01-01
NIST is applying their Real-time Control System (RCS) methodology for control of ground vehicles for both the U.S. Army Researh Lab, as part of the DOD's Unmanned Ground Vehicles program, and for the Department of Transportation's Intelligent Vehicle/Highway Systems (IVHS) program. The actuated vehicle, a military HMMWV, has motors for steering, brake, throttle, etc. and sensors for the dashboard gauges. For military operations, the vehicle has two modes of operation: a teleoperation mode--where an operator remotely controls the vehicle over an RF communications network; and a semi-autonomous mode called retro-traverse--where the control system uses an inertial navigation system to steer the vehicle along a prerecorded path. For the IVHS work, intelligent vision processing elements replace the human teleoperator to achieve autonomous, visually guided road following.
Li, Ang; Tan, Zhen; Fu, Chuangang; Wang, Hao; Yuan, Jie
2017-01-25
To investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years. Clinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively. Of 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ 2 =4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ 2 =4.266, P=0.039), lymph node metastasis (χ 2 =13.054, P=0.000) and pulmonary metastasis(χ 2 =35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36/1628), respectively. Logistic multivariate analysis showed that rectal cancer(OR:0.508, 95%CI:0.268 to 0.963, P=0.038), lymph node metastasis (OR:2.291, 95%CI:1.273 to 4.122, P=0.006) and metachronous pulmonary metastasis(OR:4.796, 95%CI:2.473 to 9.301, P=0.000) were the independent risk factors of metachronous bone metastasis of colorectal cancer within 5 years. Patients with rectal cancer, lymph node metastasis and metachronous pulmonary metastasis are high risk groups of metachronous bone metastasis after radical resection of colorectal cancer within 5 years.
Optimal Path Planning Program for Autonomous Speed Sprayer in Orchard Using Order-Picking Algorithm
NASA Astrophysics Data System (ADS)
Park, T. S.; Park, S. J.; Hwang, K. Y.; Cho, S. I.
This study was conducted to develop a software program which computes optimal path for autonomous navigation in orchard, especially for speed sprayer. Possibilities of autonomous navigation in orchard were shown by other researches which have minimized distance error between planned path and performed path. But, research of planning an optimal path for speed sprayer in orchard is hardly founded. In this study, a digital map and a database for orchard which contains GPS coordinate information (coordinates of trees and boundary of orchard) and entity information (heights and widths of trees, radius of main stem of trees, disease of trees) was designed. An orderpicking algorithm which has been used for management of warehouse was used to calculate optimum path based on the digital map. Database for digital map was created by using Microsoft Access and graphic interface for database was made by using Microsoft Visual C++ 6.0. It was possible to search and display information about boundary of an orchard, locations of trees, daily plan for scattering chemicals and plan optimal path on different orchard based on digital map, on each circumstance (starting speed sprayer in different location, scattering chemicals for only selected trees).
Autonomous Space Processor for Orbital Debris (ASPOD)
NASA Technical Reports Server (NTRS)
Ramohalli, Kumar; Mitchell, Dominique; Taft, Brett
1992-01-01
A project in the Advanced Design Program at the University of Arizona is described. The project is named the Autonomous Space Processor for Orbital Debris (ASPOD) and is a Universities Space Research Association (USRA) sponsored design project. The development of ASPOD and the students' abilities in designing and building a prototype spacecraft are the ultimate goals of this project. This year's focus entailed the development of a secondary robotic arm and end-effector to work in tandem with an existent arm in the removal of orbital debris. The new arm features the introduction of composite materials and a linear drive system, thus producing a light-weight and more accurate prototype. The main characteristic of the end-effector design is that it incorporates all of the motors and gearing internally, thus not subjecting them to the harsh space environment. Furthermore, the arm and the end-effector are automated by a control system with positional feedback. This system is composed of magnetic and optical encoders connected to a 486 PC via two servo-motor controller cards. Programming a series of basic routines and sub-routines allowed the ASPOD prototype to become more autonomous. The new system is expected to perform specified tasks with a positional accuracy of 0.5 cm.
DARPA Orbital Express program: effecting a revolution in space-based systems
NASA Astrophysics Data System (ADS)
Whelan, David A.; Adler, E. A.; Wilson, Samuel B., III; Roesler, Gordon M., Jr.
2000-11-01
A primary goal of the Defense Advanced Research Projects Agency is to develop innovative, high-risk technologies with the potential of a revolutionary impact on missions of the Department of Defense. DARPA is developing a space experiment to prove the feasibility of autonomous on- orbit servicing of spacecraft. The Orbital Express program will demonstrate autonomous on-orbit refueling, as well as autonomous delivery of a small payload representing an avionics upgrade package. The maneuverability provided to spacecraft from a ready refueling infrastructure will enable radical new capabilities for the military, civil and commercial spacecraft. Module replacement has the potential to extend bus lifetimes, and to upgrade the performance of key subsystems (e.g. processors) at the pace of technology development. The Orbital Express technology development effort will include the necessary autonomy for a viable servicing infrastructure; a universal interface for docking, refueling and module transfers; and a spacecraft bus design compatible with this servicing concept. The servicer spacecraft of the future may be able to act as a host platform for microsatellites, extending their capabilities while reducing risk. An infrastructure based on Orbital Express also benefits from, and stimulates the development of, lower-cost launch strategies.
Grant, Catharina C; Mongwe, Lot; Janse van Rensburg, Dina C; Fletcher, Lizelle; Wood, Paola S; Terblanche, Etrisia; du Toit, Peet J
2016-09-01
Grant, CC, Mongwe, L, Janse van Rensburg, DC, Fletcher, L, Wood, PS, Terblanche, E, and du Toit, PJ. The difference between exercise-induced autonomic and fitness changes measured after 12 and 20 weeks of medium-to-high intensity military training. J Strength Cond Res 30(9): 2453-2459, 2016-The aim of this study was to compare the physical fitness, based on VO2max and exercise-induced cardiac autonomic changes, measured by heart rate variability (HRV) of 12 weeks with 20 weeks of training in the South African National Defence Force. Recruits (n = 154) participated in a medium-to-high intensity exercise intervention (daily energy expenditure: 8,485 kJ·d). The significant effect on VO2max between weeks 1 and 12 (48.57, SD = 9.25 vs. 53.36, SD = 7.21] did not continue during weeks 12-20 (53.36, SD = 7.21 vs. 53.87, SD = 7.87). No changes in the supine low frequency (LF)/high frequency (HF) (0.48, SD = 0.51 vs. 0.41, SD = 0.64) or the standing LF/HF (4.02, SD = 5.14 vs. 3.91, SD = 5.28), an indicator of autonomic balance and a possible indicator of overtraining syndrome, suggests that overtraining did not take place during weeks 12-20. This was confirmed with further decreases in supine and standing heart rate. However, the power of the vagal-induced variability continued to increase after 12 weeks. Increased vagal influence without concurrent change in autonomic balance may be interpreted as decreased sympathetic cardiac control. It is important to note that although no fitness changes were detected, positive cardiac autonomic conditioning did continue between weeks 12 and 20, as measured by increased vagal-induced HRV and decreased sympathetic influence on cardiac control. Results may be extrapolated to training in the normal population/athletes after a medium-to-high intensity exercise program, as this intervention was a closely monitored and standardized exercise program.
Coactivator SRC-2–dependent metabolic reprogramming mediates prostate cancer survival and metastasis
Dasgupta, Subhamoy; Putluri, Nagireddy; Long, Weiwen; Zhang, Bin; Wang, Jianghua; Kaushik, Akash K.; Arnold, James M.; Bhowmik, Salil K.; Stashi, Erin; Brennan, Christine A.; Rajapakshe, Kimal; Coarfa, Cristian; Mitsiades, Nicholas; Ittmann, Michael M.; Chinnaiyan, Arul M.; Sreekumar, Arun; O’Malley, Bert W.
2015-01-01
Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2–driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer. PMID:25664849
TWIST1-WDR5-Hottip regulates Hoxa9 chromatin to facilitate prostate cancer metastasis
Malek, Reem; Gajula, Rajendra P.; Williams, Russell D.; Nghiem, Belinda; Simons, Brian W.; Nugent, Katriana; Wang, Hailun; Taparra, Kekoa; Lemtiri-Chlieh, Ghali; Yoon, Arum R.; True, Lawrence; An, Steven S.; DeWeese, Theodore L.; Ross, Ashley E.; Schaeffer, Edward M.; Pienta, Kenneth J.; Hurley, Paula J.; Morrissey, Colm; Tran, Phuoc T.
2017-01-01
TWIST1 is a transcription factor critical for development which can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are co-expressed in mouse prostate and then silenced post-natally. Here we report that TWIST1 and HOXA9 co-expression are re-activated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival. TWIST1 formed a complex with WDR5 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromatin in the Hox/HOX cluster during development. TWIST1 overexpression led to co-enrichment of TWIST1 and WDR5 as well increased H3K4me3 chromatin at the Hoxa9/HOXA9 promoter which was dependent on WDR5. Expression of WDR5 and Hottip/HOTTIP was also required for TWIST1-induced upregulation of HOXA9 and aggressive cellular phenotypes such as invasion and migration. Pharmacological inhibition of HOXA9 prevented TWIST1-induced aggressive prostate cancer cellular phenotypes in vitro and metastasis in vivo. This study demonstrates a novel mechanism by which TWIST1 regulates chromatin and gene expression by cooperating with the COMPASS-like complex to increase H3K4 trimethylation at target gene promoters. Our findings highlight a TWIST1-HOXA9 embryonic prostate developmental program that is reactivated during prostate cancer metastasis and is therapeutically targetable. PMID:28484075
Yu, Chia-Pin; Lin, Chia-Min; Tsai, Ming-Jer; Tsai, Yu-Chieh; Chen, Chun-Yu
2017-08-09
The present study investigated changes in autonomic nervous system activity and emotions after a short (2 h) forest bathing program in the Xitou Nature Education Area (XNEA), Taiwan. One hundred and twenty-eight (60.0 ± 7.44 years) middle-aged and elderly participants were recruited. Physiological responses, pulse rate, systolic and diastolic blood pressure, heart rate variability (HRV), and psychological indices were measured before and after the program. We observed that pulse rate, systolic and diastolic blood pressure were significantly lower after the program, which indicated physiological benefits from stress recovery. The Profile of Mood States negative mood subscale scores of "tension-anxiety", "anger-hostility", "fatigue-inertia", "depression-dejection", and "confusion-bewilderment" were significantly lower, whereas the positive mood subscale score of "vigor-activity" was higher. Furthermore, participants exhibited significantly lower anxiety levels according to the State-Trait Anxiety Inventory. However, changes in sympathetic and parasympathetic nerve activity were nonsignificant. Our study determined that the short forest bathing program is a promising therapeutic method for enhancing heart rate and blood pressure functions as well as an effective psychological relaxation strategy for middle-aged and elderly individuals.
Yu, Chia-Pin; Lin, Chia-Min; Tsai, Ming-Jer; Tsai, Yu-Chieh; Chen, Chun-Yu
2017-01-01
The present study investigated changes in autonomic nervous system activity and emotions after a short (2 h) forest bathing program in the Xitou Nature Education Area (XNEA), Taiwan. One hundred and twenty-eight (60.0 ± 7.44 years) middle-aged and elderly participants were recruited. Physiological responses, pulse rate, systolic and diastolic blood pressure, heart rate variability (HRV), and psychological indices were measured before and after the program. We observed that pulse rate, systolic and diastolic blood pressure were significantly lower after the program, which indicated physiological benefits from stress recovery. The Profile of Mood States negative mood subscale scores of “tension-anxiety”, “anger-hostility”, “fatigue-inertia”, “depression-dejection”, and “confusion-bewilderment” were significantly lower, whereas the positive mood subscale score of “vigor-activity” was higher. Furthermore, participants exhibited significantly lower anxiety levels according to the State-Trait Anxiety Inventory. However, changes in sympathetic and parasympathetic nerve activity were nonsignificant. Our study determined that the short forest bathing program is a promising therapeutic method for enhancing heart rate and blood pressure functions as well as an effective psychological relaxation strategy for middle-aged and elderly individuals. PMID:28792445
Reprogramming Enhancers to Drive Metastasis.
Mostoslavsky, Raul; Bardeesy, Nabeel
2017-08-24
Acquired molecular changes can promote the spreading of primary tumor cells to distant tissues. In this issue of Cell, Roe et al. show that metastatic progression of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcriptional program specifying early endodermal stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.
An advanced terrain modeler for an autonomous planetary rover
NASA Technical Reports Server (NTRS)
Hunter, E. L.
1980-01-01
A roving vehicle capable of autonomously exploring the surface of an alien world is under development and an advanced terrain modeler to characterize the possible paths of the rover as hazardous or safe is presented. This advanced terrain modeler has several improvements over the Troiani modeler that include: a crosspath analysis, better determination of hazards on slopes, and methods for dealing with missing returns at the extremities of the sensor field. The results from a package of programs to simulate the roving vehicle are then examined and compared to results from the Troiani modeler.
Sample Return Robot Centennial Challenge
2012-06-16
NASA Program Manager for Centennial Challenges Sam Ortega help show a young visitor how to drive a rover as part of the interactive NASA Mars rover exhibit during the Worcester Polytechnic Institute (WPI) "TouchTomorrow" education and outreach event that was held in tandem with the NASA-WPI Sample Return Robot Centennial Challenge on Saturday, June 16, 2012 in Worcester, Mass. The NASA-WPI challenge tasked robotic teams to build autonomous robots that can identify, collect and return samples. NASA needs autonomous robotic capability for future planetary exploration. Photo Credit: (NASA/Bill Ingalls)
NASA Technical Reports Server (NTRS)
Jones, William Henry
2005-01-01
The Project Integration Architecture (PIA) uses object-oriented technology to implement self-revelation and semantic infusion through class derivation. That is, the kind of an object can be discovered through program inquiry and the well-known, well-defined meaning of that object can be utilized as a result of that discovery. This technology has already been demonstrated by the PIA effort in its parameter object classes. It is proposed that, by building on this technology, an autonomous, automatic, goal-seeking, solution system may be devised.
1994-10-01
Furthermore, a systemic -wide incrL ase in capillary permeability raises the interstitial colloid osmotic pressure ([’i) and reverses the [’p-H’i gradient in...1:40 Mayuki Aibiki, Medical University of South Carolina Abstract #1 Role of Autonomic Nervous System in Acute Pressor Effects Induced by 3.5...YOUNES 33,36 Zwischenberger 21 Zwissler 35 SALT 6 Teton Village, Wyoming Abstract 1 ROLE OF AUTONOMIC NERVOUS SYSTEM IN ACUTE PRESSOR EFFECTS INDUCED BY
Tian, Honglai; Guan, Donghui; Li, Jianmin
2018-06-01
Osteosarcoma (OS), the most common malignant bone tumor, accounts for the heavy healthy threat in the period of children and adolescents. OS occurrence usually correlates with early metastasis and high death rate. This study aimed to better understand the mechanism of OS metastasis.Based on Gene Expression Omnibus (GEO) database, we downloaded 4 expression profile data sets associated with OS metastasis, and selected differential expressed genes. Weighted gene co-expression network analysis (WGCNA) approach allowed us to investigate the most OS metastasis-correlated module. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to give annotation of selected OS metastasis-associated genes.We select 897 differential expressed genes from OS metastasis and OS non-metastasis groups. Based on these selected genes, WGCNA further explored 142 genes included in the most OS metastasis-correlated module. Gene Ontology functional and KEGG pathway enrichment analyses showed that significantly OS metastasis-associated genes were involved in pathway correlated with insulin-like growth factor binding.Our research figured out several potential molecules participating in metastasis process and factors acting as biomarker. With this study, we could better explore the mechanism of OS metastasis and further discover more therapy targets.
Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.
Megwalu, Uchechukwu C; Sirjani, Davud
2017-04-01
Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.
Therapeutic possibilities and opportunities for comparative oncopathology.
Kaiser, H E
1993-01-01
In reviewing abnormal growth, we may distinguish autonomous and nonautonomous growth processes. The highest diversification is reached in the autonomous non-self-limiting processes, the malignant neoplasms which, if not treated, are characterized by extensive growth and progression. In their development these processes exhibit autonomy on one hand and heterogeneity on the other. Neoplastic and related diseases are extremely complex. It is unacceptable to view them exclusively as genetic or metabolic diseases, or merely as the tumor itself, including its progressive stages, as evidenced in neoplastic metastasis. All these characteristics appear in the different types of neoplastic malignomas, e.g. genetic variations in the neoplastic cells from the normal cells of the parent tissue(s). Included here are tumor progression and cloning of the neoplastic cells, stagewise development of host metabolism and of tumor metabolism; neoplastic hereditary and endocrine-like syndromes as well as paraneoplastic syndromes and cachexia. Neoplastic progression, as observed in the metastatic cascade, derives from the cells of the primary tumor. In contrast, multiple primary tumors originate from different host tissues, whereas the syndromes themselves constitute a symptom complex developing in a neoplasm-bearing host and cannot be assigned to local or distant spread of neoplasms. The only possible explanation for these apparently contrasting processes lies in the interaction of tumor and host metabolism, which seemingly varies in tumor-bearing hosts and in those cases where the tumor has been surgical removed. Antigens and other compounds again show an increase with the usually ensuing secondary tumor spread, a course which provides the basis for most deaths from cancer.
Wallhead, Tristan L; Garn, Alex C; Vidoni, Carla
2014-12-01
The purpose of this study was to examine the effect of a high school sport education curriculum program on students' motivation for physical education and leisure-time physical activity. Participants were 568 high school students enrolled in the required physical education programs at 2 schools, 1 taught using sport education and the 2nd using a multiactivity model of instruction. A motivational profile survey, which included student psychological need satisfaction, autonomous motives, perceived effort and enjoyment in physical education, and physical activity intention and behavior, was completed by all participants prior to and at the end of the 2-year physical education program. Mixed-model analysis of variance tests revealed that the students in the sport education program reported greater increases in perceived effort and enjoyment of the program compared with the students taught within the multiactivity model. Hierarchical multiple regression analyses showed that these positive affective outcomes were facilitated by the development of more autonomous forms of motivation. RESULTS revealed limited support for the direct transfer of motivation from a sport education program to increases in leisure-time physical activity behavior. Sport education facilitates more internalized forms of student motivation in required physical education programs, but without the provision of an appropriately designed extracurricular outlet, the potential of transfer to leisure-time physical activity may not be achieved.
COX-2 – A Novel Target for Reducing Tumor Angiogenesis and Metastasis | Center for Cancer Research
Angiogenesis is essential for tumor growth and metastasis, by supplying a steady stream of nutrients, removing waste, and providing tumor cells access to other sites in the body. The vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a key role in tumor-mediated angiogenesis, and this pathway is the target of monoclonal antibodies and tyrosine kinase inhibitors (TKIs) that have been approved to treat patients with cancer. Unfortunately, tumors can use alternative angiogenesis mechanisms to escape VEGF pathway blockade, but these alternate pathways are not well understood. Brad St. Croix, Ph.D., of CCR’s Mouse Cancer Genetics Program, along with Lihong Xu, Ph.D., a Postdoctoral Fellow in the St. Croix laboratory, and colleagues set out to identify VEGF-independent mediators of tumor angiogenesis.
ERIC Educational Resources Information Center
Eddow, Christine
2017-01-01
Physical therapy is a branch of healthcare that has advanced from an ancillary support role to an autonomous doctoral level profession in only two decades. Enrollment in physical therapy programs is increasing while resources and program length remain limited, leaving academic leaders challenged to identify instructional methods to manage…
Genetic programs can be compressed and autonomously decompressed in live cells
NASA Astrophysics Data System (ADS)
Lapique, Nicolas; Benenson, Yaakov
2018-04-01
Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes1-13 and genetically encoded circuits in live cells14-21. Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity22 of two bits per nucleotide23. In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum24. We hypothesize that the biological function of a genetic program can be preserved while reducing the length of its DNA encoding and increasing the information content per nucleotide. Here we support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we choose an RNAi cell classifier circuit25 that comprises redundant DNA sequences and is therefore amenable for compression, as are many other complex gene circuits15,18,26-28. In one example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs. The compression principles applied to gene circuits can enable fitting complex genetic programs into DNA delivery vehicles with limited cargo capacity, and storing compressed and biologically inert programs in vivo for on-demand activation.
Star Identification Without Attitude Knowledge: Testing with X-Ray Timing Experiment Data
NASA Technical Reports Server (NTRS)
Ketchum, Eleanor
1997-01-01
As the budget for the scientific exploration of space shrinks, the need for more autonomous spacecraft increases. For a spacecraft with a star tracker, the ability to determinate attitude from a lost in space state autonomously requires the capability to identify the stars in the field of view of the tracker. Although there have been efforts to produce autonomous star trackers which perform this function internally, many programs cannot afford these sensors. The author previously presented a method for identifying stars without a priori attitude knowledge specifically targeted for onboard computers as it minimizes the necessary computer storage. The method has previously been tested with simulated data. This paper provides results of star identification without a priori attitude knowledge using flight data from two 8 by 8 degree charge coupled device star trackers onboard the X-Ray Timing Experiment.
Working and Learning with Knowledge in the Lobes of a Humanoid's Mind
NASA Technical Reports Server (NTRS)
Ambrose, Robert; Savely, Robert; Bluethmann, William; Kortenkamp, David
2003-01-01
Humanoid class robots must have sufficient dexterity to assist people and work in an environment designed for human comfort and productivity. This dexterity, in particular the ability to use tools, requires a cognitive understanding of self and the world that exceeds contemporary robotics. Our hypothesis is that the sense-think-act paradigm that has proven so successful for autonomous robots is missing one or more key elements that will be needed for humanoids to meet their full potential as autonomous human assistants. This key ingredient is knowledge. The presented work includes experiments conducted on the Robonaut system, a NASA and the Defense Advanced research Projects Agency (DARPA) joint project, and includes collaborative efforts with a DARPA Mobile Autonomous Robot Software technical program team of researchers at NASA, MIT, USC, NRL, UMass and Vanderbilt. The paper reports on results in the areas of human-robot interaction (human tracking, gesture recognition, natural language, supervised control), perception (stereo vision, object identification, object pose estimation), autonomous grasping (tactile sensing, grasp reflex, grasp stability) and learning (human instruction, task level sequences, and sensorimotor association).
Integrated System for Autonomous Science
NASA Technical Reports Server (NTRS)
Chien, Steve; Sherwood, Robert; Tran, Daniel; Cichy, Benjamin; Davies, Ashley; Castano, Rebecca; Rabideau, Gregg; Frye, Stuart; Trout, Bruce; Shulman, Seth;
2006-01-01
The New Millennium Program Space Technology 6 Project Autonomous Sciencecraft software implements an integrated system for autonomous planning and execution of scientific, engineering, and spacecraft-coordination actions. A prior version of this software was reported in "The TechSat 21 Autonomous Sciencecraft Experiment" (NPO-30784), NASA Tech Briefs, Vol. 28, No. 3 (March 2004), page 33. This software is now in continuous use aboard the Earth Orbiter 1 (EO-1) spacecraft mission and is being adapted for use in the Mars Odyssey and Mars Exploration Rovers missions. This software enables EO-1 to detect and respond to such events of scientific interest as volcanic activity, flooding, and freezing and thawing of water. It uses classification algorithms to analyze imagery onboard to detect changes, including events of scientific interest. Detection of such events triggers acquisition of follow-up imagery. The mission-planning component of the software develops a response plan that accounts for visibility of targets and operational constraints. The plan is then executed under control by a task-execution component of the software that is capable of responding to anomalies.
Heinen, Laura; Heuser, Thomas; Steinschulte, Alexander; Walther, Andreas
2017-08-09
Enzymes regulate complex functions and active behavior in natural systems and have shown increasing prospect for developing self-regulating soft matter systems. Striving for advanced autonomous hydrogel materials with fully programmable, self-regulated life cycles, we combine two enzymes with an antagonistic pH-modulating effect in a feedback-controlled biocatalytic reaction network (BRN) and couple it to pH-responsive DNA hydrogels to realize hydrogel systems with distinct preprogrammable lag times and lifetimes in closed systems. The BRN enables precise and orthogonal internal temporal control of the "ON" and "OFF" switching times of the temporary gel state by modulation of programmable, nonlinear pH changes. The time scales are tunable by variation of the enzyme concentrations and additional buffer substances. The resulting material system operates in full autonomy after injection of the chemical fuels driving the BRN. The concept may open new applications inherent to DNA hydrogels, for instance, autonomous shape memory behavior for soft robotics. We further foresee general applicability to achieve autonomous life cycles in other pH switchable systems.
NASA Technical Reports Server (NTRS)
Martin-Alvarez, A.; Hayati, S.; Volpe, R.; Petras, R.
1999-01-01
An advanced design and implementation of a Control Architecture for Long Range Autonomous Planetary Rovers is presented using a hierarchical top-down task decomposition, and the common structure of each design is presented based on feedback control theory. Graphical programming is presented as a common intuitive language for the design when a large design team is composed of managers, architecture designers, engineers, programmers, and maintenance personnel. The whole design of the control architecture consists in the classic control concepts of cyclic data processing and event-driven reaction to achieve all the reasoning and behaviors needed. For this purpose, a commercial graphical tool is presented that includes the mentioned control capabilities. Messages queues are used for inter-communication among control functions, allowing Artificial Intelligence (AI) reasoning techniques based on queue manipulation. Experimental results show a highly autonomous control system running in real time on top the JPL micro-rover Rocky 7 controlling simultaneously several robotic devices. This paper validates the sinergy between Artificial Intelligence and classic control concepts in having in advanced Control Architecture for Long Range Autonomous Planetary Rovers.
Lin, Shu-Ling; Huang, Ching-Ya; Shiu, Shau-Ping; Yeh, Shu-Hui
2015-08-01
Mental health professionals experiencing work-related stress may experience burn out, leading to a negative impact on their organization and patients. The aim of this study was to examine the effects of yoga classes on work-related stress, stress adaptation, and autonomic nerve activity among mental health professionals. A randomized controlled trial was used, which compared the outcomes between the experimental (e.g., yoga program) and the control groups (e.g., no yoga exercise) for 12 weeks. Work-related stress and stress adaptation were assessed before and after the program. Heart rate variability (HRV) was measured at baseline, midpoint through the weekly yoga classes (6 weeks), and postintervention (after 12 weeks of yoga classes). The results showed that the mental health professionals in the yoga group experienced a significant reduction in work-related stress (t = -6.225, p < .001), and a significant enhancement of stress adaptation (t = 2.128, p = .042). Participants in the control group revealed no significant changes. Comparing the mean differences in pre- and posttest scores between yoga and control groups, we found the yoga group significantly decreased work-related stress (t = -3.216, p = .002), but there was no significant change in stress adaptation (p = .084). While controlling for the pretest scores of work-related stress, participants in yoga, but not the control group, revealed a significant increase in autonomic nerve activity at midpoint (6 weeks) test (t = -2.799, p = .007), and at posttest (12 weeks; t = -2.099, p = .040). Because mental health professionals experienced a reduction in work-related stress and an increase in autonomic nerve activity in a weekly yoga program for 12 weeks, clinicians, administrators, and educators should offer yoga classes as a strategy to help health professionals reduce their work-related stress and balance autonomic nerve activities. © 2015 The Authors. Worldviews on Evidence-Based Nursing published by Wiley Periodicals, Inc. on behalf of Society for Worldviews on Evidence-Based Nursing.
Chen, Junli; Chang, Hui; Peng, Xiaoli; Gu, Yeyun; Yi, Long; Zhang, Qianyong; Zhu, Jundong; Mi, Mantian
2016-06-27
The epithelial to mesenchymal transition (EMT) is a critical developmental program in cancer stem cell (CSC) maintenance and in cancer metastasis. Here, our study found that 3,6-DHF could effectively inhibit EMT in BC cells in vitro and in vivo. 3,6-DHF effectively inhibits the formation and proliferation of BCSCs, and consequently reduces the tumor-initiating capacity of tumor cells in NOD/SCID mice. Optical in vivo imaging of cancer metastasis showed that 3,6-DHF administration suppresses the lung metastasis of BC cells in vivo. Further studies indicated that 3,6-DHF down-regulates Notch1, NICD, Hes-1 and c-Myc, consequently decreasing the formation of the functional transcriptional unit of NICD-CSL-MAML, causing Notch signaling inactivation in BC cells. Over-expression of Notch1 or inhibition of miR-34a significantly reduced the inhibitory effects of 3,6-DHF on EMT, CSCs, as well as cells migration and invasion in BC cells. These data indicated that 3,6-DHF effectively inhibits EMT and CSCs, as well as cells migration and invasion in BC cells, in which miR-34a-mediated Notch1 down-regulation plays a crucial role.
HRV Analysis to Identify Stages of Home-based Telerehabilitation Exercise.
Jeong, In Cheol; Finkelstein, Joseph
2014-01-01
Spectral analysis of heart rate variability (HRV) has been widely used to investigate activity of autonomous nervous system. Previous studies demonstrated potential of analysis of short-term sequences of heart rate data in a time domain for continuous monitoring of levels of physiological stress however the value of HRV parameters in frequency domain for monitoring cycling exercise has not been established. The goal of this study was to assess whether HRV parameters in frequency domain differ depending on a stage of cycling exercise. We compared major HRV parameters in high, low and very low frequency ranges during rest, height of exercise, and recovery during cycling exercise. Our results indicated responsiveness of frequency-domain indices to different phases of cycling exercise program and their potential in monitoring autonomic balance and stress levels as a part of a tailored home-based telerehabilitation program.
Ambler - An autonomous rover for planetary exploration
NASA Technical Reports Server (NTRS)
Bares, John; Hebert, Martial; Kanade, Takeo; Krotkov, Eric; Mitchell, Tom
1989-01-01
The authors are building a prototype legged rover, called the Ambler (loosely an acronym for autonomous mobile exploration robot) and testing it on full-scale, rugged terrain of the sort that might be encountered on the Martian surface. They present an overview of their research program, focusing on locomotion, perception, planning, and control. They summarize some of the most important goals and requirements of a rover design and describe how locomotion, perception, and planning systems can satisfy these requirements. Since the program is relatively young (one year old at the time of writing) they identify issues and approaches and describe work in progress rather than report results. It is expected that many of the technologies developed will be applicable to other planetary bodies and to terrestrial concerns such as hazardous waste assessment and remediation, ocean floor exploration, and mining.
ERIC Educational Resources Information Center
Chalies, Sebastien; Bruno-Meard, Francoise; Meard, Jacques; Bertone, Stefano
2010-01-01
This study evaluated the impact of a specific program on the training of preservice teachers; the program consisted of alternating periods of "condensed" and autonomous classroom work and training sequences with university supervisors and cooperating teachers in order to prepare for these practical work periods. Borrowing from an original…
ERIC Educational Resources Information Center
Kaplan, Haya; Madjar, Nir
2015-01-01
Promoting pro-environmental behaviours (PEBs) among students is a major concern for educators. The present article presents an educational program based on a self-determination theory framework (SDT; Deci & Ryan, 2000) and a study demonstrating that working according to the theoretical principles presented in the program leads to the desired…
ERIC Educational Resources Information Center
Altintas, Tugba; Gunes, Ali; Sayan, Hamiyet
2016-01-01
Peer learning or, as commonly expressed, peer-assisted learning (PAL) involves school students who actively assist others to learn and in turn benefit from an effective learning environment. This research was designed to support students in becoming more autonomous in their learning, help them enhance their confidence level in tackling computer…
NASA Astrophysics Data System (ADS)
Lederer, S. M.; Hickson, P.; Cowardin, H. M.; Buckalew, B.; Frith, J.; Alliss, R.
In June 2015, the construction of the Meter Class Autonomous Telescope was completed and MCAT saw the light of the stars for the first time. In 2017, MCAT was newly dedicated as the Eugene Stansbery-MCAT telescope by NASA’s Orbital Debris Program Office (ODPO), in honour of his inspiration and dedication to this newest optical member of the NASA ODPO. Since that time, MCAT has viewed the skies with one engineering camera and two scientific cameras, and the ODPO optical team has begun the process of vetting the entire system. The full system vetting includes verification and validation of: (1) the hardware comprising the system (e.g. the telescopes and its instruments, the dome, weather systems, all-sky camera, FLIR cloud infrared camera, etc.), (2) the custom-written Observatory Control System (OCS) master software designed to autonomously control this complex system of instruments, each with its own control software, and (3) the custom written Orbital Debris Processing software for post-processing the data. ES-MCAT is now capable of autonomous observing to include Geosyncronous survey, TLE (Two-line element) tracking of individual catalogued debris at all orbital regimes (Low-Earth Orbit all the way to Geosynchronous (GEO) orbit), tracking at specified non-sidereal rates, as well as sidereal rates for proper calibration with standard stars. Ultimately, the data will be used for validation of NASA’s Orbital Debris Engineering Model, ORDEM, which aids in engineering designs of spacecraft that require knowledge of the orbital debris environment and long-term risks for collisions with Resident Space Objects (RSOs).
NASA Technical Reports Server (NTRS)
Lederer, S. M.; Hickson, P.; Cowardin, H. M.; Buckalew, B.; Frith, J.; Alliss, R.
2017-01-01
In June 2015, the construction of the Meter Class Autonomous Telescope was completed and MCAT saw the light of the stars for the first time. In 2017, MCAT was newly dedicated as the Eugene Stansbery-MCAT telescope by NASA's Orbital Debris Program Office (ODPO), in honor of his inspiration and dedication to this newest optical member of the NASA ODPO. Since that time, MCAT has viewed the skies with one engineering camera and two scientific cameras, and the ODPO optical team has begun the process of vetting the entire system. The full system vetting includes verification and validation of: (1) the hardware comprising the system (e.g. the telescopes and its instruments, the dome, weather systems, all-sky camera, FLIR cloud infrared camera, etc.), (2) the custom-written Observatory Control System (OCS) master software designed to autonomously control this complex system of instruments, each with its own control software, and (3) the custom written Orbital Debris Processing software for post-processing the data. ES-MCAT is now capable of autonomous observing to include Geosynchronous survey, TLE (Two-line element) tracking of individual catalogued debris at all orbital regimes (Low-Earth Orbit all the way to Geosynchronous (GEO) orbit), tracking at specified non-sidereal rates, as well as sidereal rates for proper calibration with standard stars. Ultimately, the data will be used for validation of NASA's Orbital Debris Engineering Model, ORDEM, which aids in engineering designs of spacecraft that require knowledge of the orbital debris environment and long-term risks for collisions with Resident Space Objects (RSOs).
Toward a core nutraceutical program for cancer management.
McCarty, Mark F; Block, Keith I
2006-06-01
As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroombeta-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, beta-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and beta-hydroxy-beta-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-B activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.
Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.
Purushotham, A; Shamil, E; Cariati, M; Agbaje, O; Muhidin, A; Gillett, C; Mera, A; Sivanadiyan, K; Harries, M; Sullivan, R; Pinder, S E; Garmo, H; Holmberg, L
2014-07-01
Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood. Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006. Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis. These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.
MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.
Cheng, Dantong; Zhao, Senlin; Tang, Huamei; Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Jiang, Weiliang; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai
2016-07-19
Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4
Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai
2016-01-01
Background Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results miR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer. PMID:27286257
[Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].
Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X
2018-02-09
Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( P< 0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.
Hu, Dongzhi; Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Yao, Yunfeng; Gu, Jin
2013-08-01
The liver and lung are the organs most commonly affected by metastasis in colorectal cancer (CRC), and the interaction of chemokines and chemokine receptors (CKRs) plays an important role in the metastatic process. The aim of this study was to investigate the organ specificity of CKRs in CRC distant metastasis. Surgical specimens of primary tumours from 46 patients with metachronous distant metastases were retrieved retrospectively (20 lung metastases; 26 liver metastases). As a control, the records of 29 patients without distant metastases were randomly retrieved from our database, and their specimens were reassessed. The expression rates of CKRs, including CCR6, CXCR2, and CXCR4, were determined by immunohistochemistry, and were compared among the groups. The expression rates of CCR6 and CXCR2 were both significantly higher in the metastasis group than in the non-metastasis group (P < 0.05), but there was no statistical difference between the lung metastasis and liver metastasis subgroups. The expression of CXCR4 was not significantly different between the metastasis and non-metastasis groups. Multivariable analysis suggested that preoperative serum carcinoembryonic antigen level, CCR6 and CXCR2 were independent factors associated with distant metastasis. The expression of CCR6 and CXCR2 in CRC could predict metachronous distant metastasis, but they have no organ specificity for metastasis. © 2013 John Wiley & Sons Ltd.
Ye, Wei-Liang; Zhao, Yi-Pu; Cheng, Ying; Liu, Dao-Zhou; Cui, Han; Liu, Miao; Zhang, Bang-Le; Mei, Qi-Bing; Zhou, Si-Yuan
2018-01-16
In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis.
Autonomous Vehicle Mission Planning Using AI (Artificial Intelligence) Techniques.
1985-12-01
it uses are declarative patterns that encode facts about how goals may give rise to - . plans. The program processes a story a sentence at a time...the planning process. By separating the knowledge about how to plan from the specific domain knowledge, an understander can use this knowledge about how ...path planning program developed in a previous thesis effort will be incorporated into the overall program in order to demonstrate the operating system
Choi, Joon Ho; Byun, Byung Hyun; Lim, Ilhan; Moon, Hansol; Park, Jihyun; Chang, Kyoung Jin; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo
2018-04-01
We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC). Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient. Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis ( p = 0.017) and I-131 non-avid lung metastasis ( p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not ( p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 ( p = 0.029) for macronodular lung metastasis and 3.29 ( p = 0.079) for I-131 non-avid lung metastasis. Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.
Tumour mutation status and sites of metastasis in patients with cutaneous melanoma.
Adler, Nikki R; Wolfe, Rory; Kelly, John W; Haydon, Andrew; McArthur, Grant A; McLean, Catriona A; Mar, Victoria J
2017-09-26
Cutaneous melanoma can metastasise haematogenously and/or lymphogenously to form satellite/in-transit, lymph node or distant metastasis. This study aimed to determine if BRAF and NRAS mutant and wild-type tumours differ in their site of first tumour metastasis and anatomical metastatic pathway. Prospective cohort of patients with a histologically confirmed primary cutaneous melanoma at three tertiary referral centres in Melbourne, Australia from 2010 to 2015. Multinomial regression determined clinical, histological and mutational factors associated with the site of first metastasis and metastatic pathway. Of 1048 patients, 306 (29%) developed metastasis over a median 4.7 year follow-up period. 73 (24%), 192 (63%) and 41 (13%) developed distant, regional lymph node and satellite/in-transit metastasis as the first site of metastasis, respectively. BRAF mutation was associated with lymph node metastasis (adjusted RRR 2.46 95% CI 1.07-5.69, P=0.04) and sentinel lymph node positivity (adjusted odds ratio [aOR] OR 1.55, 95% CI 1.14-2.10, P=0.005). BRAF mutation and NRAS mutation were associated with increased odds of developing liver metastasis (aOR 3.09, 95% CI 1.49-6.42, P=0.003; aOR 3.17, 95% CI 1.32-7.58, P=0.01) and central nervous system (CNS) metastasis (aOR 4.65, 95% CI 2.23-9.69, P<0.001; aOR 4.03, 95% CI 1.72-9.44, P=0.001). NRAS mutation was associated with lung metastasis (aOR 2.44, 95% CI 1.21-4.93, P=0.01). BRAF mutation was found to be associated with lymph node metastasis as first metastasis and sentinel lymph node positivity. BRAF and NRAS mutations were associated with CNS and liver metastasis and NRAS mutation with lung metastasis. If these findings are validated in additional prospective studies, a role for heightened visceral organ surveillance may be warranted in patients with tumours harbouring these somatic mutations.
Brooks, Danielle; Zimmer, Alexandra; Wakefield, Lalage; Lyle, L Tiffany; Difilippantonio, Simone; Tucci, Fabio C; Illiano, Stephane; Annunziata, Christina M; Steeg, Patricia S
2018-05-04
The lysophosphatidic acid receptor 1 (LPAR1) is mechanistically implicated in both tumor metastasis and tissue fibrosis. Previously, metastasis was increased when fulminant fibrosis was first induced in mice, suggesting a direct connection between these processes. The current report examined the extent of metastasis-induced fibrosis in breast cancer model systems, and tested the metastasis preventive efficacy and fibrosis attenuation of antagonists for LPAR1 and Idiopathic Pulmonary Fibrosis (IPF) in breast and ovarian cancer models. Staining analysis demonstrated only focal, low-moderate levels of fibrosis in lungs from eleven metastasis model systems. Two orally available LPAR1 antagonists, SAR100842 and EPGN9878, significantly inhibited breast cancer motility to LPA in vitro . Both compounds were negative for metastasis prevention and failed to reduce fibrosis in the experimental MDA-MB-231T and spontaneous murine 4T1 in vivo breast cancer metastasis models. SAR100842 demonstrated only occasional reductions in invasive metastases in the SKOV3 and OVCAR5 ovarian cancer experimental metastasis models. Two approved drugs for IPF, nintedanib and pirfenidone, were investigated. Both were ineffective at preventing MDA-MB-231T metastasis, with no attenuation of fibrosis. In summary, metastasis-induced fibrosis is only a minor component of metastasis in untreated progressive breast cancer. LPAR1 antagonists, despite in vitro evidence of specificity and efficacy, were ineffective in vivo as oral agents, as were approved IPF drugs. The data argue against LPAR1 and fibrosis as monotherapy targets for metastasis prevention in triple-negative breast cancer and ovarian cancer.
Analysis of metastasis associated signal regulatory network in colorectal cancer.
Qi, Lu; Ding, Yanqing
2018-06-18
Metastasis is a key factor that affects the survival and prognosis of colorectal cancer patients. To elucidate molecular mechanism associated with the metastasis of colorectal cancer, genes related to the metastasis time of colorectal cancer were screened. Then, a network was constructed with this genes. Data was obtained from colorectal cancer expression profile. Molecular mechanism elucidated the time of tumor metastasis and the expression of genes related to colorectal cancer. We found that metastasis-promoting and metastasis-inhibiting networks included protein hubs of high connectivity. These protein hubs were components of organelles. Some ribosomal proteins promoted the metastasis of colorectal cancer. In some components of organelles, such as proteasomes, mitochondrial ribosome, ATP synthase, and splicing factors, the metastasis of colorectal cancer was inhibited by some sections of these organelles. After performing survival analysis of proteins in organelles, joint survival curve of proteins was constructed in ribosomal network. This joint survival curve showed metastasis was promoted in patients with colorectal cancer (P = 0.0022939). Joint survival curve of proteins was plotted against proteasomes (P = 7 e-07), mitochondrial ribosome (P = 0.0001157), ATP synthase (P = 0.0001936), and splicing factors (P = 1.35e-05). These curves indicate that metastasis of colorectal cancer can be inhibited. After analyzing proteins that bind with organelle components, we also found that some proteins were associated with the time of colorectal cancer metastasis. Hence, different cellular components play different roles in the metastasis of colorectal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.
DuBois, Steven G.; London, Wendy B.; Zhang, Yang; Matthay, Katherine K.; Monclair, Tom; Ambros, Peter F.; Cohn, Susan L.; Pearson, Andrew; Diller, Lisa
2009-01-01
Background Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database. Procedure The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis. Results Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (p < 0.02 in each case). Five-year overall survival ± standard error for patients with lung metastasis was 34.5% ± 6.8% compared to 44.7% ± 1.3% for patients without lung metastasis (p=0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome. Conclusions Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome. PMID:18649370
TWIST1-WDR5-Hottip Regulates Hoxa9 Chromatin to Facilitate Prostate Cancer Metastasis.
Malek, Reem; Gajula, Rajendra P; Williams, Russell D; Nghiem, Belinda; Simons, Brian W; Nugent, Katriana; Wang, Hailun; Taparra, Kekoa; Lemtiri-Chlieh, Ghali; Yoon, Arum R; True, Lawrence; An, Steven S; DeWeese, Theodore L; Ross, Ashley E; Schaeffer, Edward M; Pienta, Kenneth J; Hurley, Paula J; Morrissey, Colm; Tran, Phuoc T
2017-06-15
TWIST1 is a transcription factor critical for development that can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are coexpressed in mouse prostate and then silenced postnatally. Here we report that TWIST1 and HOXA9 coexpression are reactivated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival. TWIST1 formed a complex with WDR5 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromatin in the Hox/HOX cluster during development. TWIST1 overexpression led to coenrichment of TWIST1 and WDR5 as well as increased H3K4me3 chromatin at the Hoxa9/HOXA9 promoter, which was dependent on WDR5. Expression of WDR5 and Hottip/HOTTIP was also required for TWIST1-induced upregulation of HOXA9 and aggressive cellular phenotypes such as invasion and migration. Pharmacologic inhibition of HOXA9 prevented TWIST1-induced aggressive prostate cancer cellular phenotypes in vitro and metastasis in vivo This study demonstrates a novel mechanism by which TWIST1 regulates chromatin and gene expression by cooperating with the COMPASS-like complex to increase H3K4 trimethylation at target gene promoters. Our findings highlight a TWIST1-HOXA9 embryonic prostate developmental program that is reactivated during prostate cancer metastasis and is therapeutically targetable. Cancer Res; 77(12); 3181-93. ©2017 AACR . ©2017 American Association for Cancer Research.
Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming
2014-01-01
Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.
NASA Astrophysics Data System (ADS)
Shane, David J.; Rufo, Michael A.; Berkemeier, Matthew D.; Alberts, Joel A.
2012-06-01
The Autonomous Urban Reconnaissance Ingress System (AURIS™) addresses a significant limitation of current military and first responder robotics technology: the inability of reconnaissance robots to open doors. Leveraging user testing as a baseline, the program has derived specifications necessary for military personnel to open doors with fielded UGVs (Unmanned Ground Vehicles), and evaluates the technology's impact on operational mission areas: duration, timing, and user patience in developing a tactically relevant, safe, and effective system. Funding is provided through the US ARMY Tank Automotive Research, Development and Engineering Center (TARDEC) and the project represents a leap forward in perception, autonomy, robotic implements, and coordinated payload operation in UGVs. This paper describes high level details of specification generation, status of the last phase of development, an advanced view of the system autonomy capability, and a short look ahead towards the ongoing work on this compelling and important technology.
Memory and modularity in cell-fate decision making
NASA Astrophysics Data System (ADS)
Norman, Thomas M.; Lord, Nathan D.; Paulsson, Johan; Losick, Richard
2013-11-01
Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is `memoryless', exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.
Mobile Autonomous Humanoid Assistant
NASA Technical Reports Server (NTRS)
Diftler, M. A.; Ambrose, R. O.; Tyree, K. S.; Goza, S. M.; Huber, E. L.
2004-01-01
A mobile autonomous humanoid robot is assisting human co-workers at the Johnson Space Center with tool handling tasks. This robot combines the upper body of the National Aeronautics and Space Administration (NASA)/Defense Advanced Research Projects Agency (DARPA) Robonaut system with a Segway(TradeMark) Robotic Mobility Platform yielding a dexterous, maneuverable humanoid perfect for aiding human co-workers in a range of environments. This system uses stereo vision to locate human team mates and tools and a navigation system that uses laser range and vision data to follow humans while avoiding obstacles. Tactile sensors provide information to grasping algorithms for efficient tool exchanges. The autonomous architecture utilizes these pre-programmed skills to form human assistant behaviors. The initial behavior demonstrates a robust capability to assist a human by acquiring a tool from a remotely located individual and then following the human in a cluttered environment with the tool for future use.
Autonomous RPOD Technology Challenges for the Coming Decade
NASA Technical Reports Server (NTRS)
Naasz, Bo J.; Moreau, Michael C.
2012-01-01
Rendezvous Proximity Operations and Docking (RPOD) technologies are important to a wide range of future space endeavors. This paper will review some of the recent and ongoing activities related to autonomous RPOD capabilities and summarize the current state of the art. Gaps are identified where future investments are necessary to successfully execute some of the missions likely to be conducted within the next ten years. A proposed RPOD technology roadmap that meets the broad needs of NASA's future missions will be outlined, and ongoing activities at OSFC in support of a future satellite servicing mission are presented. The case presented shows that an evolutionary, stair-step technology development program. including a robust campaign of coordinated ground tests and space-based system-level technology demonstration missions, will ultimately yield a multi-use main-stream autonomous RPOD capability suite with cross-cutting benefits across a wide range of future applications.
Exploiting map plans as resources for action
NASA Technical Reports Server (NTRS)
Payton, David
1989-01-01
When plans are used as programs for controlling the action of autonomous or teleoperated robots, their abstract representation can easily obscure a great deal of the critical knowledge that originally led to the planned course of action. An autonomous vehicle experiment is highlighted which illustrates how the information barriers created by abstraction can result in undesirable action. It is then shown how the same task can be performed correctly using plans as a resource for action. As a result of this simple change in outlook, problems requiring opportunistic reaction to unexpected changes in the environment can be solved.
Damage Detection and Verification System (DDVS) for In-Situ Health Monitoring
NASA Technical Reports Server (NTRS)
Williams, Martha K.; Lewis, Mark; Szafran, J.; Shelton, C.; Ludwig, L.; Gibson, T.; Lane, J.; Trautwein, T.
2015-01-01
Project presentation for Game Changing Program Smart Book Release. Detection and Verification System (DDVS) expands the Flat Surface Damage Detection System (FSDDS) sensory panels damage detection capabilities and includes an autonomous inspection capability utilizing cameras and dynamic computer vision algorithms to verify system health. Objectives of this formulation task are to establish the concept of operations, formulate the system requirements for a potential ISS flight experiment, and develop a preliminary design of an autonomous inspection capability system that will be demonstrated as a proof-of-concept ground based damage detection and inspection system.
Safety Verification of a Fault Tolerant Reconfigurable Autonomous Goal-Based Robotic Control System
NASA Technical Reports Server (NTRS)
Braman, Julia M. B.; Murray, Richard M; Wagner, David A.
2007-01-01
Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System (MDS), developed at the Jet Propulsion Laboratory, takes a goal-based control approach. In this paper, a method for converting goal network control programs into linear hybrid systems is developed. The linear hybrid system can then be verified for safety in the presence of failures using existing symbolic model checkers. An example task is simulated in MDS and successfully verified using HyTech, a symbolic model checking software for linear hybrid systems.
Ali, S M; Reisner, L A; King, B; Cao, A; Auner, G; Klein, M; Pandya, A K
2008-01-01
A redesigned motion control system for the medical robot Aesop allows automating and programming its movements. An IR eye tracking system has been integrated with this control interface to implement an intelligent, autonomous eye gaze-based laparoscopic positioning system. A laparoscopic camera held by Aesop can be moved based on the data from the eye tracking interface to keep the user's gaze point region at the center of a video feedback monitor. This system setup provides autonomous camera control that works around the surgeon, providing an optimal robotic camera platform.
Goldie, Catherine L; Brown, C Ann; Hains, Sylvia M J; Parlow, Joel L; Birtwhistle, Richard
2013-10-01
The effects of a 12-week low-intensity exercise conditioning program (walking) on blood pressure (BP), heart rate (HR), rate-pressure product (RPP), and cardiac autonomic function were measured in 40 sedentary women with hypertension. Women were assigned to either an exercise group (n = 20) or a control group (n = 20), matched for β-blockade treatment. They underwent testing at the beginning and at the end of the 12-week study period in three conditions: supine rest, standing, and low-intensity steady state exercise. The exercise group participated in a 12-week, low-intensity walking program, while the control group continued with usual sedentary activity. Compared with the control group, women in the exercise group showed reductions in systolic and diastolic BP and RPP (i.e., the estimated cardiac workload). β-Blockers increased baroreflex sensitivity and lowered BP and HR in all participants; however, those in the exercise group showed the effects of both treatments: a greater reduction in HR and RPP. The combination of exercise training and β-blockade produces cardiac and autonomic adaptations that are not observed with either treatment alone, suggesting that β-blockade enhances the conditioning effects of low-intensity exercise in women with hypertension.
A Hybrid FPGA/Tilera Compute Element for Autonomous Hazard Detection and Navigation
NASA Technical Reports Server (NTRS)
Villalpando, Carlos Y.; Werner, Robert A.; Carson, John M., III; Khanoyan, Garen; Stern, Ryan A.; Trawny, Nikolas
2013-01-01
To increase safety for future missions landing on other planetary or lunar bodies, the Autonomous Landing and Hazard Avoidance Technology (ALHAT) program is developing an integrated sensor for autonomous surface analysis and hazard determination. The ALHAT Hazard Detection System (HDS) consists of a Flash LIDAR for measuring the topography of the landing site, a gimbal to scan across the terrain, and an Inertial Measurement Unit (IMU), along with terrain analysis algorithms to identify the landing site and the local hazards. An FPGA and Manycore processor system was developed to interface all the devices in the HDS, to provide high-resolution timing to accurately measure system state, and to run the surface analysis algorithms quickly and efficiently. In this paper, we will describe how we integrated COTS components such as an FPGA evaluation board, a TILExpress64, and multi-threaded/multi-core aware software to build the HDS Compute Element (HDSCE). The ALHAT program is also working with the NASA Morpheus Project and has integrated the HDS as a sensor on the Morpheus Lander. This paper will also describe how the HDS is integrated with the Morpheus lander and the results of the initial test flights with the HDS installed. We will also describe future improvements to the HDSCE.
A hybrid FPGA/Tilera compute element for autonomous hazard detection and navigation
NASA Astrophysics Data System (ADS)
Villalpando, C. Y.; Werner, R. A.; Carson, J. M.; Khanoyan, G.; Stern, R. A.; Trawny, N.
To increase safety for future missions landing on other planetary or lunar bodies, the Autonomous Landing and Hazard Avoidance Technology (ALHAT) program is developing an integrated sensor for autonomous surface analysis and hazard determination. The ALHAT Hazard Detection System (HDS) consists of a Flash LIDAR for measuring the topography of the landing site, a gimbal to scan across the terrain, and an Inertial Measurement Unit (IMU), along with terrain analysis algorithms to identify the landing site and the local hazards. An FPGA and Manycore processor system was developed to interface all the devices in the HDS, to provide high-resolution timing to accurately measure system state, and to run the surface analysis algorithms quickly and efficiently. In this paper, we will describe how we integrated COTS components such as an FPGA evaluation board, a TILExpress64, and multi-threaded/multi-core aware software to build the HDS Compute Element (HDSCE). The ALHAT program is also working with the NASA Morpheus Project and has integrated the HDS as a sensor on the Morpheus Lander. This paper will also describe how the HDS is integrated with the Morpheus lander and the results of the initial test flights with the HDS installed. We will also describe future improvements to the HDSCE.
NASA Technical Reports Server (NTRS)
Ramohalli, Kumar; Mitchell, Dominique; Taft, Brett; Chinnock, Paul; Kutz, Bjoern
1992-01-01
This paper is regarding a project in the Advanced Design Program at the University of Arizona. The project is named the Autonomous Space Processor for Orbital Debris (ASPOD) and is a NASA/Universities Space Research Association (USRA) sponsored design project. The development of ASPOD and the students' abilities in designing and building a prototype spacecraft are the ultimate goals of this project. This year's focus entailed the development of a secondary robotic arm and end-effector to work in tandem with an existent arm in the removal of orbital debris. The new arm features the introduction of composite materials and a linear drive system, thus producing a light-weight and more accurate prototype. The main characteristic of the end-effector design is that it incorporates all of the motors and gearing internally, thus not subjecting them to the harsh space environment. Furthermore, the arm and the end-effector are automated by a control system with positional feedback. This system is composed of magnetic and optical encoders connected to a 486 PC via two servo-motor controller cards. Programming a series of basic routines and sub-routines has allowed the ASPOD prototype to become more autonomous. The new system is expected to perform specified tasks with a positional accuracy of 0.5 cm.
Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.
2014-01-01
Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747
Liang, Chao; Xu, Ligeng; Song, Guosheng; Liu, Zhuang
2016-11-07
Metastasis is directly or indirectly responsible for the majority of cancer deaths. Anti-metastasis treatment is thus the key to cure cancer. Recent development in nanomedicine has shown great promise for tackling cancer metastasis. In recent years, nanoparticle-based drug delivery systems have been extensively explored for improving cancer treatment, showing the ability to reduce the risk of tumor metastasis compared with conventional chemotherapy. Photothermal therapy, by employing nano-theranostic agents, has also been found to be able to inhibit lymphatic tumor metastasis. Moreover, the post-immunological effects of certain types of nano-therapies may also be utilized to treat tumor metastasis, presenting an exciting new avenue towards successful cancer treatment. In this review article, we would like to summarize the latest research advances in the development of various emerging nanomedicine approaches for cancer metastasis treatment, and discuss future prospects in this emerging field as well as the clinical translation potential of these techniques.
ERIC Educational Resources Information Center
Judge, Sharon; Gasset, Dolores Izuzquiza
2015-01-01
The Autonomous University of Madrid (UAM) is the first Spanish university to provide training to young people with intellectual disabilities (ID) in the university environment, which qualifies them for inclusion in the workforce. In this practice brief we describe the UAM-Prodis Patronage Chair program, a successful model used at Spanish…
ERIC Educational Resources Information Center
Levy, Sharona T.; Mioduser, David
2008-01-01
This study investigates young children's perspectives in explaining a self-regulating mobile robot, as they learn to program its behaviors from rules. We explore their descriptions of a robot in action to determine the nature of their explanatory frameworks: psychological or technological. We have also studied the role of an adult's intervention…
ERIC Educational Resources Information Center
Hoogeveen, Jeffrey L.
Founded in 1854 as the Ashmun Institute, Lincoln University in southern Pennsylvania is the nation's oldest historically black university. Classical rhetoric and canonical literature were taught at Lincoln since its founding. Lincoln's writing program emerged fully and autonomously in 1978 and grew roughly at the same time that the discipline of…
Choroidal metastasis in disseminated lung cancer: frequency and risk factors.
Kreusel, Klaus-Martin; Wiegel, Thomas; Stange, Marit; Bornfeld, Norbert; Hinkelbein, Wolfgang; Foerster, Michael H
2002-09-01
To determine frequency, risk factors, and benefit of a prospective screening for intraocular metastasis in patients with metastatic lung cancer. Consecutive observational case series. An ophthalmologic screening was performed on 84 consecutive patients suffering from metastatic lung cancer. Medical history and disease stage were evaluated in regard to the risk for intraocular metastasis. In six patients (7.1%) choroidal metastasis (CM) was detected. Choroidal metastasis was present only when at least two other organ system were affected by metastasis (P =.03). The choroid was the sixth common site of organ metastasis. Mean remaining life span in patients with CM was 1.9 (0.2-5.9) months. Choroidal metastasis is common in advanced metastatic lung cancer. However, due to the short survival of affected individuals, a systematic screening of at-risk patients for CM seems to be of limited benefit.
Terrain Perception for DEMO III
NASA Technical Reports Server (NTRS)
Manduchi, R.; Bellutta, P.; Matthies, L.; Owens, K.; Rankin, A.
2000-01-01
The Demo III program has as its primary focus the development of autonomous mobility for a small rugged cross country vehicle. In this paper we report recent progress on both stereo-based obstacle detection and terrain cover color-based classification.
Mechanism of Twist1-Induced Invasion in Breast Cancer Metastasis
2012-01-01
Breast Cancer Metastasis PRINCIPAL INVESTIGATOR: Mark Adam Eckert CONTRACTING...2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanism of Twist1-Induced Invasion in Breast Cancer Metastasis 5b. GRANT NUMBER W81XWH-09-1...an important mediator of breast cancer metastasis by driving the epithelial-mesenchymal transition. We find that Twist1 promotes metastasis by
DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis.
Wang, Yufeng; Lei, Rong; Zhuang, Xueqian; Zhang, Ning; Pan, Hong; Li, Gang; Hu, Jing; Pan, Xiaoqi; Tao, Qian; Fu, Da; Xiao, Jianru; Chin, Y Eugene; Kang, Yibin; Yang, Qifeng; Hu, Guohong
2014-04-01
Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-β signaling; however, little is known about how the TGF-β pathway is regulated during bone metastasis. Here we report that deleted in liver cancer 1 (DLC1) is an important regulator of TGF-β responses and osteolytic metastasis of breast cancer cells. In murine models, breast cancer cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis. Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested osteolysis and accelerated death in mice, while DLC1 overexpression suppressed bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated SMAD3 linker region phosphorylation and TGF-β-induced expression of parathyroid hormone-like hormone (PTHLH), leading to osteoclast maturation for osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK effectively reduced PTHLH production and breast cancer bone metastasis in vitro and in vivo. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. Overall, our findings define a stroma-dependent paradigm of Rho signaling in cancer and implicate Rho-TGF-β crosstalk in osteolytic bone metastasis.
Koi, Yumiko; Koga, Chinami; Akiyoshi, Sayuri; Masuda, Takanobu; Ijichi, Hideki; Nakamura, Yoshiaki; Ishida, Mayumi; Ohno, Shinji; Tokunaga, Eriko
2018-03-01
Previous studies have suggested that the presence of visceral metastasis is a parameter useful in predicting the treatment efficacy of fulvestrant in patients with advanced breast cancer. We retrospectively examined the association between treatment efficacy and presence of visceral metastasis in 75 patients with hormone receptor-positive recurrent breast cancer who were treated with fulvestrant or no more than five lines of other endocrine monotherapy after recurrence. Nineteen patients received fulvestrant, 10 of whom had visceral metastasis. The median time to progression was 4 months for the overall study population; it was significantly longer for patients with non-visceral metastasis (5.4 months; 95% confidence interval=3.7-11.2 months) than for those with visceral metastasis (3.3 months; 95% confidence interval, 0.4-5.3 months; p=0.01). No differences in time to progression were found between the groups of patients with visceral metastasis and non-visceral metastasis who underwent other endocrine therapies. Fulvestrant is more effective for patients with non-visceral metastasis of recurrent breast cancer with than for those with visceral metastasis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Molecular implementation of simple logic programs.
Ran, Tom; Kaplan, Shai; Shapiro, Ehud
2009-10-01
Autonomous programmable computing devices made of biomolecules could interact with a biological environment and be used in future biological and medical applications. Biomolecular implementations of finite automata and logic gates have already been developed. Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions. Using molecular representations of facts such as Man(Socrates) and rules such as Mortal(X) <-- Man(X) (Every Man is Mortal), the system can answer molecular queries such as Mortal(Socrates)? (Is Socrates Mortal?) and Mortal(X)? (Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision. A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result. This prototype is the first simple programming language with a molecular-scale implementation.
Line grouping using perceptual saliency and structure prediction for car detection in traffic scenes
NASA Astrophysics Data System (ADS)
Denasi, Sandra; Quaglia, Giorgio
1993-08-01
Autonomous and guide assisted vehicles make a heavy use of computer vision techniques to perceive the environment where they move. In this context, the European PROMETHEUS program is carrying on activities in order to develop autonomous vehicle monitoring that assists people to achieve safer driving. Car detection is one of the topics that are faced by the program. Our contribution proposes the development of this task in two stages: the localization of areas of interest and the formulation of object hypotheses. In particular, the present paper proposes a new approach that builds structural descriptions of objects from edge segmentations by using geometrical organization. This approach has been applied to the detection of cars in traffic scenes. We have analyzed images taken from a moving vehicle in order to formulate obstacle hypotheses: preliminary results confirm the efficiency of the method.
Overview of computational control research at UT Austin
NASA Technical Reports Server (NTRS)
Bong, Wie
1989-01-01
An overview of current research activities at UT Austin is presented to discuss certain technical issues in the following areas: (1) Computer-Aided Nonlinear Control Design: In this project, the describing function method is employed for the nonlinear control analysis and design of a flexible spacecraft equipped with pulse modulated reaction jets. INCA program has been enhanced to allow the numerical calculation of describing functions as well as the nonlinear limit cycle analysis capability in the frequency domain; (2) Robust Linear Quadratic Gaussian (LQG) Compensator Synthesis: Robust control design techniques and software tools are developed for flexible space structures with parameter uncertainty. In particular, an interactive, robust multivariable control design capability is being developed for INCA program; and (3) LQR-Based Autonomous Control System for the Space Station: In this project, real time implementation of LQR-based autonomous control system is investigated for the space station with time-varying inertias and with significant multibody dynamic interactions.
NASA Technical Reports Server (NTRS)
Savely, Robert T.; Loftin, R. Bowen
1990-01-01
Training is a major endeavor in all modern societies. Common training methods include training manuals, formal classes, procedural computer programs, simulations, and on-the-job training. NASA's training approach has focussed primarily on on-the-job training in a simulation environment for both crew and ground based personnel. NASA must explore new approaches to training for the 1990's and beyond. Specific autonomous training systems are described which are based on artificial intelligence technology for use by NASA astronauts, flight controllers, and ground based support personnel that show an alternative to current training systems. In addition to these specific systems, the evolution of a general architecture for autonomous intelligent training systems that integrates many of the features of traditional training programs with artificial intelligence techniques is presented. These Intelligent Computer Aided Training (ICAT) systems would provide much of the same experience that could be gained from the best on-the-job training.
Liu, Ziwen; Sun, Mengqing; Xiao, Yiding; Yang, Jing; Zhang, Taiping; Zhao, Yupei
2017-07-01
To study the clinicopathological characteristics and the risk factors of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in differentiated thyroid carcinoma; and to identify the indication for LN-prRLN dissection. We treated 145 patients with differentiated thyroid carcinoma with appropriate surgical intervention. The specimens were examined by the pathologists. The right paratracheal lymph nodes were divided into two groups: anterior or posterior to right recurrent laryngeal nerve (VIa or VIp compartment, respectively). We recorded the clinical characteristics, histopathological features of the primary tumors, and lymph node metastasis of the patients. The results were statistically analyzed. There were 85 patients (58.6%) with central lymph node metastasis, of whom 61 (42.1%) had metastasis in VIa compartment; 16 patients (11.0%) had VIp subdistrict metastasis; and 25 patients had lateral lymph node metastasis. Multiplicity, larger tumor (≥1 cm), and coexistence of central lymph node metastasis, VIa compartment metastasis, and lateral lymph node metastasis were all significantly related with LN-prRLN metastasis, while sex, age, location of the tumor, and extrathyroid extension of the tumor showed no significant relation (p > 0.05). The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons. Copyright © 2016. Published by Elsevier Taiwan.
MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis
Tomasetti, Marco; Amati, Monica; Santarelli, Lory; Neuzil, Jiri
2016-01-01
The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance. PMID:27213336
A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene.
Gobeil, Stephane; Zhu, Xiaochun; Doillon, Charles J; Green, Michael R
2008-11-01
Metastasis suppressor genes inhibit one or more steps required for metastasis without affecting primary tumor formation. Due to the complexity of the metastatic process, the development of experimental approaches for identifying genes involved in metastasis prevention has been challenging. Here we describe a genome-wide RNAi screening strategy to identify candidate metastasis suppressor genes. Following expression in weakly metastatic B16-F0 mouse melanoma cells, shRNAs were selected based upon enhanced satellite colony formation in a three-dimensional cell culture system and confirmed in a mouse experimental metastasis assay. Using this approach we discovered 22 genes whose knockdown increased metastasis without affecting primary tumor growth. We focused on one of these genes, Gas1 (Growth arrest-specific 1), because we found that it was substantially down-regulated in highly metastatic B16-F10 melanoma cells, which contributed to the high metastatic potential of this mouse cell line. We further demonstrated that Gas1 has all the expected properties of a melanoma tumor suppressor including: suppression of metastasis in a spontaneous metastasis assay, promotion of apoptosis following dissemination of cells to secondary sites, and frequent down-regulation in human melanoma metastasis-derived cell lines and metastatic tumor samples. Thus, we developed a genome-wide shRNA screening strategy that enables the discovery of new metastasis suppressor genes.
[A retrospective analysis on occult neck lymphatic metastasis in early tongue cancer].
Gong, Q L; Bian, C; Liu, H
2016-10-07
Objective: To investigate the number and level of occult neck lymphatic metastasis for squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ, and the relationship between cell differentiation and occult neck lymphatic metastasis. Methods: A total of 101 cases diagnosed preoperatively as having squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ (cT1/T2N0M0) between January 2005 and April 2015 were analysed retrospectively. Whether presence of occult neck lymphatic metastasis in these cases was studied. Results: Occult neck lymphatic metastases were found in 22 (21.78%) of 101 cases, 10 men and 12 women, with an age range of 22 to 83 years. There was not statistically significant association between tumor size or cell differentiation and occult neck lymphatic metastasis ( P >0.05). The metastasis occurred most commonly in level Ⅱ, followed by levelsⅠ, Ⅲ and Ⅳ. There was no lymph node metastasis in Level Ⅴ. There were total 20 cases with occult neck lymphatic metastasis in at least one of levelⅠ, Ⅱ, Ⅲ(90.9%), One of these case was skipping metastasis in level Ⅲ(4.6%). Conclusion: The early tongue cancer has a high rate of occult lymph metastasis, which occurs commonly in levels Ⅱ, Ⅰ and Ⅲ, but there is not significant association between the metastasis and tumor size or cell differentiation.
Publications of the NASA Controlled Ecological Life Support System (CELSS) Program, 1979-1989
NASA Technical Reports Server (NTRS)
Wallace, Janice S.; Powers, Janet V.
1990-01-01
Publications of research sponsored by the NASA Controlled Ecological Life Support System (CELSS) Program from 1979 to 1989 are listed. The CELSS Program encompasses research and technology with the goal of developing an autonomous bioregenerative life support system that continually recycles the solid, liquid, and gaseous materials essential for human life. The bibliography is divided into four major subject areas: food production, nutritional requirements, waste management, and systems management and control.
NASA Astrophysics Data System (ADS)
Schubert, Oliver J.; Tolle, Charles R.
2004-09-01
Over the last decade the world has seen numerous autonomous vehicle programs. Wheels and track designs are the basis for many of these vehicles. This is primarily due to four main reasons: a vast preexisting knowledge base for these designs, energy efficiency of power sources, scalability of actuators, and the lack of control systems technologies for handling alternate highly complex distributed systems. Though large efforts seek to improve the mobility of these vehicles, many limitations still exist for these systems within unstructured environments, e.g. limited mobility within industrial and nuclear accident sites where existing plant configurations have been extensively changed. These unstructured operational environments include missions for exploration, reconnaissance, and emergency recovery of objects within reconfigured or collapsed structures, e.g. bombed buildings. More importantly, these environments present a clear and present danger for direct human interactions during the initial phases of recovery operations. Clearly, the current classes of autonomous vehicles are incapable of performing in these environments. Thus the next generation of designs must include highly reconfigurable and flexible autonomous robotic platforms. This new breed of autonomous vehicles will be both highly flexible and environmentally adaptable. Presented in this paper is one of the most successful designs from nature, the snake-eel-worm (SEW). This design implements shape memory alloy (SMA) actuators which allow for scaling of the robotic SEW designs from sub-micron scale to heavy industrial implementations without major conceptual redesigns as required in traditional hydraulic, pneumatic, or motor driven systems. Autonomous vehicles based on the SEW design posses the ability to easily move between air based environments and fluid based environments with limited or no reconfiguration. Under a SEW designed vehicle, one not only achieves vastly improved maneuverability within a highly unstructured environment, but also gains robotic manipulation abilities, normally relegated as secondary add-ons within existing vehicles, all within one small condensed package. The prototype design presented includes a Beowulf style computing system for advanced guidance calculations and visualization computations. All of the design and implementation pertaining to the SEW robot discussed in this paper is the product of a student team under the summer fellowship program at the DOEs INEEL.
Advances in Decoding Breast Cancer Brain Metastasis
Zhang, Chenyu; Yu, Dihua
2016-01-01
The past decade has witnessed impressive advances in cancer treatment ushered in by targeted and immunotherapies. However, with significantly prolonged survival, upon recurrence, more patients become inflicted by brain metastasis, which is mostly refractory to all currently available therapeutic regimens. Historically, brain metastasis is an understudied area in cancer research, partly due to the dearth of appropriate experimental models that closely simulate the special biological features of metastasis in the unique brain environment; and to the sophistication of techniques required to perform in-depth studies of the extremely complex and challenging brain metastasis. Yet, with increasing clinical demand for more effective treatment options, brain metastasis research has rapidly advanced in recent years. The present review spotlights the recent major progresses in basic and translational studies of brain metastasis with focuses on new animal models, novel imaging technologies, omics “big data” resources, and some new and exciting biological insights on brain metastasis. PMID:27873078
Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice
Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue
2015-01-01
Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281
Lung Metastasis Mimicking Fingertip Infection
Soylemez, Salih; Demiroglu, Murat; Yayla, Mehmet Ali; Ozkan, Korhan; Alpan, Bugra; Ozger, Harzem
2015-01-01
Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient's pain during his terminal period, saves the functions of the limb, and increases life comfort. PMID:26236517
Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis
2013-10-01
Pharmaceuticals , Inc., Department of Defense grants PC05031 (to P.E. Thorpe) and PC080475 (to Y. Yin), an NIH-supported Small Animal Imaging Research Program...PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...Army Medical Research And Materiel Command 11. SPONSOR/MONITOR’S REPORT Fort Detrick, Maryland NUMBER(S) 21702-5012 12. DISTRIBUTION / AVAILABILITY
Yu, Q A; Ma, D K; Liu, K P; Wang, P; Xie, C M; Wu, Y H; Dai, W J; Jiang, H C
2018-03-17
To investigate risk factors associated with right paraesophageal lymph node (RPELN) metastasis in patients with papillary thyroid carcinoma (PTC) and to determine the indications for right lymph node dissection. Clinicopathologic data from 829 patients (104 men and 725 women) with PTC, operated on by the same thyroid surgery team at the First Affiliated Hospital of Harbin Medical University from January 2013 to May 2017, were analyzed. Overall, 309 patients underwent total thyroidectomy with bilateral lymph node dissection, 488 underwent right thyroid lobe and isthmic resection with right central compartment lymph node dissection, and 32 underwent near-total thyroidectomy (ipsilateral thyroid lobectomy with contralateral near-total lobectomy) with bilateral lymph node dissection. The overall rate of central compartment lymph node metastasis was 43.5% (361/829), with right central compartment lymph node and RPELN metastasis rates of 35.5% (294/829) and 19.1% (158/829), respectively. Tumor size, number, invasion, and location, lymph node metastasis, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis were associated with RPELN in the univariate analysis, whereas age and sex were not. Multivariate analysis identified tumors with a diameter ≥ 1 cm, multiple tumors, tumors located in the right lobe, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis as independent risk factors for RPELN metastasis. Lymph node dissection, including RPELN dissection, should be performed for patients with PTC with a tumor diameter ≥ 1 cm, multiple tumors, right-lobe tumors, right central compartment lymph node metastasis, or suspected lateral compartment lymph node metastasis.
Sakairi, Yuichi; Yoshino, Ichiro; Yoshida, Shigetoshi; Suzuki, Hidemi; Tagawa, Tetsuzo; Iwata, Takekazu; Mizobuchi, Teruaki
2014-05-01
Patterns of intrapulmonary metastasis, particularly metastasis outside tumor-bearing segments, were investigated in lung cancer patients to address the rationale for segmentectomy. In a consecutive series of patients who underwent resection of two or more pulmonary segments for primary lung cancer, intrapulmonary spread patterns, such as segmental/intersegmental node metastasis and pulmonary parenchymal metastasis, were pathologically examined. Eligible 244 lesions included 167 adenocarcinomas, 66 squamous cell carcinomas, and 11 large cell carcinomas. Pathologic stages included 0 to IA (n=111), IB (n=56), IIA (n=31), IIB (n=20), IIIA (n=23), and IIIB to IV (n=3); and N1 (n=26) and N2 (n=22). Intrapulmonary spread was observed in 24 cases (9.8%). Of these, metastasis outside tumor-bearing segments was only observed in 4 cases (1.6%), and such cancer spread was more frequently seen in cases with extrapulmonary (hilar to mediastinal) nodal metastasis (7.9%) than in cases without extrapulmonary metastasis (0.5%; p=0.01). Metastasis outside tumor-bearing segments was not observed in 64 tumors with pure or mixed ground glass opacity features on computed tomography. Although tumor location (peripheral or central/intermediate) was not related to the incidence of metastasis outside tumor-bearing segments, intrapulmonary spread was observed in only 1 of 52 peripheral small (≤20 mm) tumors. Metastasis outside tumor-bearing segments is rarely observed in cases with tumors (1) without extrapulmonary nodal metastasis and (2) with ground glass opacity or peripheral small (≤20 mm) features. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Aguilar, Esther; de Mas, Igor Marin; Zodda, Erika; Marin, Silvia; Morrish, Fionnuala; Selivanov, Vitaly; Meca-Cortés, Óscar; Delowar, Hossain; Pons, Mònica; Izquierdo, Inés; Celià-Terrassa, Toni; de Atauri, Pedro; Centelles, Josep J; Hockenbery, David; Thomson, Timothy M; Cascante, Marta
2016-01-01
In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analysis that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis. PMID:27146024
Autonomous, Computer-Based Behavioral Health Countermeasure Evaluation at HI-SEAS Mars Analog.
Anderson, Allison P; Fellows, Abigail M; Binsted, Kim A; Hegel, Mark T; Buckey, Jay C
Living in an isolated, confined environment (ICE) can induce conflict, stress, and depression. Computer-based behavioral health countermeasures are appealing for training and treatment in ICEs because they provide confidentiality and do not require communication with the outside environment. We evaluated the Virtual Space Station (VSS), a suite of interactive computer-delivered psychological training and treatment programs, at the Hawaii Space Exploration Analog and Simulation (HI-SEAS) III expedition. Six subjects (3 male, 3 female) spent 8 mo in group-isolation and used the Conflict, Stress, and Depression modules in the VSS. Survey evaluations, data collected within the program, and postdeployment interviews were collected. This crew dealt with behavioral health issues common to ICEs. The VSS proved to be a valuable resource and was used both as intended, and in unanticipated ways, to help maintain behavioral health. The Conflict and Stress Modules were rated as highly acceptable (1.8 on a 7-point Likert scale). The crew identified a total of 13 stressors and worked on 9 problems through the VSS. Opinions about the modules were highly individualized. Crewmembers identified exercises in the VSS that were applicable and not applicable to their needs. Additional content to improve the program was identified. Autonomous, confidential training and treatment for behavioral health issues will need to be a critical component of long duration spaceflight travel. This work provides an evaluation of such a tool in a relevant ICE. Anderson AP, Fellows AM, Binsted KA, Hegel MT, Buckey JC. Autonomous, computer-based behavioral health countermeasure evaluation at HI-SEAS Mars analog. Aerosp Med Hum Perform. 2016; 87(11):912-920.
NASA Technical Reports Server (NTRS)
Siders, Jeffrey A.; Smith, Robert H.
2004-01-01
The continued assembly and operation of the International Space Station (ISS) is the cornerstone within NASA's overall Strategic P an. As indicated in NASA's Integrated Space Transportation Plan (ISTP), the International Space Station requires Shuttle to fly through at least the middle of the next decade to complete assembly of the Station, provide crew transport, and to provide heavy lift up and down mass capability. The ISTP reflects a tight coupling among the Station, Shuttle, and OSP programs to support our Nation's space goal . While the Shuttle is a critical component of this ISTP, there is a new emphasis for the need to achieve greater efficiency and safety in transporting crews to and from the Space Station. This need is being addressed through the Orbital Space Plane (OSP) Program. However, the OSP is being designed to "complement" the Shuttle as the primary means for crew transfer, and will not replace all the Shuttle's capabilities. The unique heavy lift capabilities of the Space Shuttle is essential for both ISS, as well as other potential missions extending beyond low Earth orbit. One concept under discussion to better fulfill this role of a heavy lift carrier, is the transformation of the Shuttle to an "un-piloted" autonomous system. This concept would eliminate the loss of crew risk, while providing a substantial increase in payload to orbit capability. Using the guidelines reflected in the NASA ISTP, the autonomous Shuttle a simplified concept of operations can be described as; "a re-supply of cargo to the ISS through the use of an un-piloted Shuttle vehicle from launch through landing". Although this is the primary mission profile, the other major consideration in developing an autonomous Shuttle is maintaining a crew transportation capability to ISS as an assured human access to space capability.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, W.-J.; Chen, W.-K.; Wang, C.-J.
2008-01-15
Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration andmore » anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of {beta}4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin {beta}4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By histological and gross examination of mouse lung and real-time PCR analysis of human alu in host tissues, it showed that apigenin, wortmannin, as well as anti-{beta}4 antibody all inhibit HGF-promoted metastasis. These data support the inhibitory effect of apigenin on HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and integrin {beta}4 function.« less
Leader-follower function for autonomous military convoys
NASA Astrophysics Data System (ADS)
Vasseur, Laurent; Lecointe, Olivier; Dento, Jerome; Cherfaoui, Nourrdine; Marion, Vincent; Morillon, Joel G.
2004-09-01
The French Military Robotic Study Program (introduced in Aerosense 2003), sponsored by the French Defense Procurement Agency and managed by Thales Airborne Systems as the prime contractor, focuses on about 15 robotic themes which can provide an immediate "operational added value." The paper details the "robotic convoy" theme (named TEL1), which main purpose is to develop a robotic leader-follower function so that several unmanned vehicles can autonomously follow teleoperated, autonomous or on-board driven leader. Two modes have been implemented: Perceptive follower: each autonomous follower anticipates the trajectory of the vehicle in front of it, thanks to a dedicated perception equipment. This mode is mainly based on the use of perceptive data, without any communication link between leader and follower (to lower the cost of future mass development and extend the operational capabilities). Delayed follower: the leader records its path and transmits it to the follower; the follower is able to follow the recorded trajectory again at any delayed time. This mode uses localization data got from inertial measurements. The paper presents both modes with detailed algorithms and the results got from the military acceptance tests performed on wheeled 4x4 vehicles (DARDS French ATD).
Global Precipitation Measurement (GPM) Orbit Design and Autonomous Maneuvers
NASA Technical Reports Server (NTRS)
Folta, David; Mendelsohn, Chad
2003-01-01
The NASA Goddard Space Flight Center's Global Precipitation Measurement (GPM) mission will meet a challenge of measuring worldwide precipitation every three hours. The GPM spacecraft, part of a constellation, will be required to maintain a circular orbit in a high drag environment to accomplish this challenge. Analysis by the Flight Dynamics Analysis Branch has shown that the prime orbit altitude of 40% is necessary to prevent ground track repeating. Combined with goals to minimize maneuver impacts to science data collection and enabling reasonable long-term orbit predictions, the GPM project has decided to fly an autonomous maneuver system. This system is a derivative of the successful New Millennium Program technology flown onboard the Earth Observing-1 mission. This paper presents the driving science requirements and goals of the mission and shows how they will be met. Analysis of the orbit optimization and the AV requirements for several ballistic properties are presented. The architecture of the autonomous maneuvering system to meet the goals and requirements is presented along with simulations using a GPM prototype. Additionally, the use of the GPM autonomous system to mitigate possible collision avoidance and to aid other spacecraft systems during navigation outages is explored.
Semi autonomous mine detection system
DOE Office of Scientific and Technical Information (OSTI.GOV)
Douglas Few; Roelof Versteeg; Herman Herman
2010-04-01
CMMAD is a risk reduction effort for the AMDS program. As part of CMMAD, multiple instances of semi autonomous robotic mine detection systems were created. Each instance consists of a robotic vehicle equipped with sensors required for navigation and marking, a countermine sensors and a number of integrated software packages which provide for real time processing of the countermine sensor data as well as integrated control of the robotic vehicle, the sensor actuator and the sensor. These systems were used to investigate critical interest functions (CIF) related to countermine robotic systems. To address the autonomy CIF, the INL developed RIKmore » was extended to allow for interaction with a mine sensor processing code (MSPC). In limited field testing this system performed well in detecting, marking and avoiding both AT and AP mines. Based on the results of the CMMAD investigation we conclude that autonomous robotic mine detection is feasible. In addition, CMMAD contributed critical technical advances with regard to sensing, data processing and sensor manipulation, which will advance the performance of future fieldable systems. As a result, no substantial technical barriers exist which preclude – from an autonomous robotic perspective – the rapid development and deployment of fieldable systems.« less
NASA Technical Reports Server (NTRS)
Rouff, Christopher A. (Inventor); Sterritt, Roy (Inventor); Truszkowski, Walter F. (Inventor); Hinchey, Michael G. (Inventor); Gracanin, Denis (Inventor); Rash, James L. (Inventor)
2011-01-01
Described herein is a method that produces fully (mathematically) tractable development of policies for autonomic systems from requirements through to code generation. This method is illustrated through an example showing how user formulated policies can be translated into a formal mode which can then be converted to code. The requirements-based programming method described provides faster, higher quality development and maintenance of autonomic systems based on user formulation of policies.Further, the systems, methods and apparatus described herein provide a way of analyzing policies for autonomic systems and facilities the generation of provably correct implementations automatically, which in turn provides reduced development time, reduced testing requirements, guarantees of correctness of the implementation with respect to the policies specified at the outset, and provides a higher degree of confidence that the policies are both complete and reasonable. The ability to specify the policy for the management of a system and then automatically generate an equivalent implementation greatly improves the quality of software, the survivability of future missions, in particular when the system will operate untended in very remote environments, and greatly reduces development lead times and costs.
Advances in diagnosis and treatment of metastatic cervical cancer
2016-01-01
Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673
Choroidal metastasis from early rectal cancer: Case report and literature review
Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki
2014-01-01
INTRODUCTION Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. PRESENTATION OF CASE A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. DISCUSSION Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. CONCLUSION This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. PMID:25460493
Choroidal metastasis from early rectal cancer: Case report and literature review.
Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki
2014-01-01
Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Inhibition of breast cancer metastasis with microRNA-302a by downregulation of CXCR4 expression.
Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk
2014-08-01
Metastasis remains a main cause of mortality from breast cancer and an unresolved issue. The purpose of this study is to investigate the role of miR-302a in the development of breast cancer metastasis mediated by CXCR4, a critical regulator of metastasis, and to identify miR-302a as an effective therapeutic agent for therapy and prevention of breast cancer metastasis. Our studies show that miR-302a expression levels were downregulated in metastatic breast cancer cells and tumor tissues. Additionally, the expression levels of miR-302a were inversely correlated with CXCR4 levels. More promisingly, miR-302a inhibited the invasion and metastasis of breast cancer cells in vitro and in vivo and reduced the expression of CXCR4. Our findings demonstrated that the repression of miR-302a levels contributes to breast cancer metastasis and restoration of miR-302a baseline expression inhibits the invasion and metastasis of breast cancer cells. These data suggest that miR-302a mimics are potential therapeutic agents for breast cancer metastasis.
Advances in diagnosis and treatment of metastatic cervical cancer.
Li, Haoran; Wu, Xiaohua; Cheng, Xi
2016-07-01
Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.
Postgraduate Education for Nurses: The Middlesex Model.
ERIC Educational Resources Information Center
Caldwell, Kay
2001-01-01
A British university's curriculum model for master's and postgraduate diploma nursing education is characterized by structured collaboration among students, clinical mentors, and academic supervisors. A professional development portfolio individualizes the program and facilitates autonomous learning. (Contains 21 references.) (SK)
DLC1-dependent parathyroid hormone–like hormone inhibition suppresses breast cancer bone metastasis
Wang, Yufeng; Lei, Rong; Zhuang, Xueqian; Zhang, Ning; Pan, Hong; Li, Gang; Hu, Jing; Pan, Xiaoqi; Tao, Qian; Fu, Da; Xiao, Jianru; Chin, Y. Eugene; Kang, Yibin; Yang, Qifeng; Hu, Guohong
2014-01-01
Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-β signaling; however, little is known about how the TGF-β pathway is regulated during bone metastasis. Here we report that deleted in liver cancer 1 (DLC1) is an important regulator of TGF-β responses and osteolytic metastasis of breast cancer cells. In murine models, breast cancer cells lacking DLC1 expression exhibited enhanced capabilities of bone metastasis. Knockdown of DLC1 in cancer cells promoted bone metastasis, leading to manifested osteolysis and accelerated death in mice, while DLC1 overexpression suppressed bone metastasis. Activation of Rho-ROCK signaling in the absence of DLC1 mediated SMAD3 linker region phosphorylation and TGF-β–induced expression of parathyroid hormone–like hormone (PTHLH), leading to osteoclast maturation for osteolytic colonization. Furthermore, pharmacological inhibition of Rho-ROCK effectively reduced PTHLH production and breast cancer bone metastasis in vitro and in vivo. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. Overall, our findings define a stroma-dependent paradigm of Rho signaling in cancer and implicate Rho–TGF-β crosstalk in osteolytic bone metastasis. PMID:24590291
Zhao, Min; Li, Zhe; Qu, Hong
2015-01-01
Metastasis suppressor genes (MS genes) are genes that play important roles in inhibiting the process of cancer metastasis without preventing growth of the primary tumor. Identification of these genes and understanding their functions are critical for investigation of cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility MS genes. However, the comprehensive illustration of diverse cellular processes regulated by metastasis suppressors during the metastasis cascade is lacking. Thus, the relationship between MS genes and cancer risk is still unclear. To unveil the cellular complexity of MS genes, we have constructed MSGene (http://MSGene.bioinfo-minzhao.org/), the first literature-based gene resource for exploring human MS genes. In total, we manually curated 194 experimentally verified MS genes and mapped to 1448 homologous genes from 17 model species. Follow-up functional analyses associated 194 human MS genes with epithelium/tissue morphogenesis and epithelia cell proliferation. In addition, pathway analysis highlights the prominent role of MS genes in activation of platelets and coagulation system in tumor metastatic cascade. Moreover, global mutation pattern of MS genes across multiple cancers may reveal common cancer metastasis mechanisms. All these results illustrate the importance of MSGene to our understanding on cell development and cancer metastasis. PMID:26486520
An, Changming; Zhang, Xiwei; Wang, Shixu; Zhang, Zongmin; Yin, Yulin; Xu, Zhengang; Tang, Pingzhang; Li, Zhengjiang
2017-01-01
Background This study aimed to evaluate superselective neck dissection (SSND) in patients with cN0 papillary thyroid carcinoma (PTC) at high risk of lateral cervical lymph node (LN) metastasis. Material/Methods This study enrolled 138 patients with PTC who underwent SSND. These patients were at high risk for LN metastasis and the rate of cervical LN metastasis was recorded. Results In all, 146 lateral neck dissections were performed in 138 patients. Intraoperative pathological data revealed LN metastasis from 55 cases, for which Level II and V dissection were performed. Ninety SSNDs were performed in the other 83 patients without metastasis identified in frozen sections. Occult lymph node metastasis (OLNM) rates were 56.8% and 43.5% in the central compartment and lateral neck, respectively. OLNM rates of Level II–VI were 17.8%, 31.5%, 36.3%, 1.4%, and 56.8%, respectively. Level VI metastasis (p<0.001), extra thyroidal extension (p=0.003), and tumor size (p=0.011) were significant factors for lateral neck LN metastasis. Conclusions SSND might be effective for early diagnosis of lateral neck metastases of PTC. Patients with OLNM should receive level II, III, and IV dissection, but level V dissection could be omitted. PMID:28469126
Sugimoto, Maki; Yasuda, Hideki; Koda, Keiji; Yamazaki, Masato; Tezuka, Tohru; Takenoue, Tomohiro; Kosugi, Chihiro; Higuchi, Ryota; Yamamoto, Shiho; Watayo, Yoshihisa; Yagawa, Yohsuke; Suzuki, Masato
2007-09-01
Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.
Task-level robot programming: Integral part of evolution from teleoperation to autonomy
NASA Technical Reports Server (NTRS)
Reynolds, James C.
1987-01-01
An explanation is presented of task-level robot programming and of how it differs from the usual interpretation of task planning for robotics. Most importantly, it is argued that the physical and mathematical basis of task-level robot programming provides inherently greater reliability than efforts to apply better known concepts from artificial intelligence (AI) to autonomous robotics. Finally, an architecture is presented that allows the integration of task-level robot programming within an evolutionary, redundant, and multi-modal framework that spans teleoperation to autonomy.
Multiple-modality program for standoff detection of roadside hazards
NASA Astrophysics Data System (ADS)
Williams, Kathryn; Middleton, Seth; Close, Ryan; Luke, Robert H.; Suri, Rajiv
2016-05-01
The U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) is executing a program to assess the performance of a variety of sensor modalities for standoff detection of roadside explosive hazards. The program objective is to identify an optimal sensor or combination of fused sensors to incorporate with autonomous detection algorithms into a system of systems for use in future route clearance operations. This paper provides an overview of the program, including a description of the sensors under consideration, sensor test events, and ongoing data analysis.
Hakai overexpression effectively induces tumour progression and metastasis in vivo.
Castosa, Raquel; Martinez-Iglesias, Olaia; Roca-Lema, Daniel; Casas-Pais, Alba; Díaz-Díaz, Andrea; Iglesias, Pilar; Santamarina, Isabel; Graña, Begoña; Calvo, Lourdes; Valladares-Ayerbes, Manuel; Concha, Ángel; Figueroa, Angélica
2018-02-22
At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues. Moreover, we confirm that Hakai overexpression in epithelial cells drives transformation in cells, a mesenchymal and invasive phenotype, accompanied by the downregulation of E-cadherin and the upregulation of N-cadherin, and an increased proliferation and an oncogenic potential. More importantly, for the first time, we have studied the role of Hakai during cancer progression in vivo. We show that Hakai-transformed MDCK cells dramatically induce tumour growth and local invasion in nude mice and tumour cells exhibit a mesenchymal phenotype. Furthermore, we have detected the presence of micrometastasis in the lung mice, further confirming Hakai role during tumour metastasis in vivo. These results lead to the consideration of Hakai as a potential new therapeutic target to block tumour development and metastasis.
BRN2, a POUerful driver of melanoma phenotype switching and metastasis.
Fane, Mitchell E; Chhabra, Yash; Smith, Aaron G; Sturm, Richard A
2018-05-21
The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behavior within the phenotype-switching model of progression. As a mediator of melanoma cell phenotype-switching it co-ordinates the transition to a de-differentiated, slow cycling and highly motile cell type. Its inverse expression relationship with MITF is believed to mediate tumour progression and metastasis within this model. Recent evidence has now outlined a potential epigenetic switching mechanism in melanoma cells driven by BRN2 expression that induces melanoma cell invasion. We summarise the role of BRN2 in tumour cell dissemination and metastasis in melanoma, while also examining it as a potential metastatic regulator in other tumour models. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
ERIC Educational Resources Information Center
Abramson, Theodore; And Others
Activities of and outcomes resulting from the State Project to Implement Career Education (SPICE) in New York City schools for the first year and a half are reported in this summative evaluation. Findings (much of which are statistical data) discussed deal almost exclusively with the elementary-junior high program, one of two autonomous programs…
ERIC Educational Resources Information Center
Peters, Richard O.
One of 10 sites chosen for multi-year funding under the National Institute of Education's rural Experimental Schools Program (ES), the New Hampshire School Supervisory Union 58 ES Project was a community-based effort, serving 3 autonomous school districts and operative between July 1973-July 1978. Serving a total population of 3,816, the project…
ERIC Educational Resources Information Center
Delisle, Marie-Noelle; Guay, Frederic; Senecal, Caroline; Larose, Simon
2009-01-01
This study proposed and tested a model based on stereotype threat theory. The hypothesis is that women who are exposed to a low percentage of women in a science program are more likely to endorse the gender stereotype that science is a male domain, which will in turn undermine their autonomous academic motivation. A total of 167 women university…
Wang, Ling; Yao, Qing; Wang, Jing; Wei, Guangquan; Li, Guoquan; Li, Dong; Ling, Rui; Chen, Jianghao
2008-02-01
To study tumour growth and metastasis in a rabbit metastatic breast cancer (MBC) model and find the most sensitive screening modality in monitoring tumour metastasis. The MBC model was established by injecting a VX2 tumour mass suspension into the mammary glands of 23 rabbits and was monitored by using physical examination, X-ray, MRI and hybrid PET/CT. Of all 23 rabbits, axillary lymph node metastasis was detected in 21 (91%) at day 33 after tumour inoculation, mediastinal node metastasis in five (22%) at day 42, abdominal node metastasis in two (9%) at day 48, lung metastasis in six (26%) at day 39, liver metastasis in three (13%) at day 48, and lumbar spine metastasis in one (4%) at day 51. Tumour invasion of pleura was found in one, stomach wall in one, and pleura and stomach concurrently in one rabbit. Sensitivity for detection of lymph node metastases was 78.6% (22/28) and 67.9% (19/28) with MRI and PET/CT, respectively; and sensitivity for detection of metastases in distant organs was 85.7% (12/14) and 71.4% (10/14), respectively. The MBC model used here exhibits fast tumour growth and extensive metastasis in a relatively short period. Its metastatic pattern is quite similar to that of human MBC and hence could be potentially used as a model for testing imaging modalities and translational research, e.g., MBC management. MRI is superior to PET/CT in monitoring tumour metastasis.
Zeng, Z. S.; Guillem, J. G.
1998-01-01
Experimental in vitro and animal data support an important role for matrix metalloproteinases (MMPs) in cancer invasion and metastasis via proteolytic degradation of the extracellular matrix (ECM). Our previous data have shown that MMP-9 mRNA is localized to the interface between liver metastasis and normal liver tissue, indicating that MMP-9 may play an important role in liver metastasis formation. In the present study, we analysed the cellular enzymatic expression of MMP-9 in 18 human colorectal cancer (CRC) liver metastasis specimens by enzyme-linked immunosorbent assay (ELISA) and zymography. ELISA analysis reveals that the latent form of MMP-9 is present in both liver metastasis and paired adjacent normal liver tissue. The mean level of the latent form of MMP-9 is 580+/-270 ng per mg total tissue protein (mean+/-s.e.) in liver metastasis vs 220+/-90 in normal liver tissue. However, this difference is not significantly different (P = 0.26). Using gelatin zymography, the 92-kDa band representative of the latent form is present in both liver metastasis and normal liver tissue. However, the 82 kDa band, representative of the active form of MMP-9, was seen only in liver metastasis. This was confirmed by Western blot analysis. Our observation of the unique presence of the active form of MMP-9 within liver metastasis suggests that proMMP-9 activation may be a pivotal event during CRC liver metastasis formation. Images Figure 3 Figure 4 PMID:9703281
Jafari-Koshki, Tohid; Mansourian, Marjan; Mokarian, Fariborz
2014-01-01
Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.
Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han
2016-08-01
Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs.
Luk, Yiu Shiobhon; Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai
2012-09-01
Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatment.
Small bowel obstruction from distant metastasis of primary breast cancer: a case report.
Oh, Seung Jae; Park, Seon Young; Kim, Ji Young; Yim, Hyunee; Jung, Yongsik; Han, Sae Hwan
2018-02-01
Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.
Shankar, Nilima; Thakur, Manisha; Tandon, Om Prakash; Saxena, Ashok Kumar; Arora, Shobha; Bhattacharya, Neena
2011-01-01
Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system. Chronic low back pain (LBP) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture. This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy. Chronic LBP patients (n=60) were recruited from the Department of Orthopaedics, GTB Hospital, Delhi. Age and sex matched healthy volunteers were selected as controls (n=30). Following a written consent, LBP patients were randomly allocated into two study groups - Group A received 10 sittings of electro acupuncture, on alternate days, at GB and UB points selected for back pain, while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy. Controls were assessed once while the patients were assessed twice, before and after completion of the treatment program (3 weeks). The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E: I ratio, 30:15 ratio, postural challenge test and sustained handgrip test. Pain intensity was measured with the visual analogue scale (VAS) and the global perceived effect (GPE). Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls (P<0.05 to P<0.001 in different variables). Following treatment, both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity. There was also a considerable relief of pain in both groups, however, the acupuncture group showed a better response (P<0.01). We conclude that there is autonomic dysfunction in chronic LBP patients. Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases.
Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo
Law, Ah-Lai; Vehlow, Anne; Kotini, Maria; Dodgson, Lauren; Soong, Daniel; Theveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham A.; Bennett, Daimark; Mayor, Roberto
2013-01-01
Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. PMID:24247431
Metastasis of osteosarcoma to the trapezius muscle: a case report
2014-01-01
Metastasis of a primary osteosarcoma to the muscles is extremely rare. As there have been few reported cases, the necessity of surgical treatment for such metastatic lesions remains controversial. We present the case of a primary osteosarcoma with development of a solitary metastasis to the trapezius muscle during chemotherapy for pulmonary metastasis. The patient was a 51-year-old man diagnosed with osteosarcoma of the right tibia. After undergoing chemotherapy and femoral amputation, he developed pulmonary metastasis. Chemotherapy was reinitiated, however, after approximately 1 year a palpable tumor was identified in the patient’s right shoulder. This tumor grew and was associated with pain in the right shoulder. It was surgically removed 3 years after the re-initiation of chemotherapy. The pathological diagnosis was osteosarcoma with metastasis to the trapezius muscle. Although the patient died of respiratory failure due to pulmonary metastasis 14 months after resection of the metastatic lesion in the trapezius muscle, no new extrapulmonary metastasis was observed after the resection. PMID:24893571
Metastasis of osteosarcoma to the trapezius muscle: a case report.
Sakamoto, Yuichiro; Yokouchi, Masahiro; Nagano, Satoshi; Shimada, Hirofumi; Nakamura, Shunsuke; Setoguchi, Takao; Kawamura, Ichiro; Ishidou, Yasuhiro; Tanimoto, Akihide; Komiya, Setsuro
2014-06-04
Metastasis of a primary osteosarcoma to the muscles is extremely rare. As there have been few reported cases, the necessity of surgical treatment for such metastatic lesions remains controversial. We present the case of a primary osteosarcoma with development of a solitary metastasis to the trapezius muscle during chemotherapy for pulmonary metastasis. The patient was a 51-year-old man diagnosed with osteosarcoma of the right tibia. After undergoing chemotherapy and femoral amputation, he developed pulmonary metastasis. Chemotherapy was reinitiated, however, after approximately 1 year a palpable tumor was identified in the patient's right shoulder. This tumor grew and was associated with pain in the right shoulder. It was surgically removed 3 years after the re-initiation of chemotherapy. The pathological diagnosis was osteosarcoma with metastasis to the trapezius muscle. Although the patient died of respiratory failure due to pulmonary metastasis 14 months after resection of the metastatic lesion in the trapezius muscle, no new extrapulmonary metastasis was observed after the resection.
RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation
Morales, Mònica; Arenas, Enrique J; Urosevic, Jelena; Guiu, Marc; Fernández, Esther; Planet, Evarist; Fenwick, Robert Bryn; Fernández-Ruiz, Sonia; Salvatella, Xavier; Reverter, David; Carracedo, Arkaitz; Massagué, Joan; Gomis, Roger R
2014-01-01
In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme. PMID:24867881
Yang, P; Liang, S-X; Huang, W-H; Zhang, H-W; Li, X-L; Xie, L-H; Du, C-W; Zhang, G-J
2014-01-01
Triple negative breast cancer is known for its visceral metastasis. We have found that CXCR4 is overexpressed in triple negative breast cancer and is associated with visceral metastasis. We further investigated whether CXCR4 is a prognostic factor affecting survival following visceral metastasis in breast cancer patients. Our results indicate that increased CXCR4 expression among breast cancer patients with visceral metastasis was positively correlated with poor overall survival (P<0.001). Silencing of CXCR4 was associated with a decrease in the tumorigenic properties of MDA-MB-231 breast cancer cells, caused reversion of EMT and suppression of MMP-9, increased apoptosis, and caused a reduced incidence of tumor lung metastasis in mice. These results are indicative of CXCR4 having a predictive role in patients with visceral metastasis and indicate that shRNA knock down of CXCR4 might be a novel therapeutic strategy to prevent breast cancer metastasis when CXCR4 is overexpressed.
Kajaia, T; Maskhulia, L; Chelidze, K; Akhalkatsi, V; Kakhabrishvili, Z
2017-03-01
Aim of the study was to compare the ANS functioning, as measured by heart rate variability (HRV), in athletes with non-functional overreaching (NFO) and overtraining syndrome (OTS) and in athletes without NFO/OTS. In 43 athletes with NFO/OTS, 40 athletes without NFO/OTS, as well as in 35 sedentary subjects the ANS function was evaluated with the Autonomic Balance Test, based on the HRV analysis of resting heart rate recordings. Results of the study show lower HRV and lower vagal influence along with increased sympathetic cardiovascular control in athletes with non-functional overreaching and particularly in athletes with overtraining, than in highly trained athletes without NFO/OTS. "Stress Response" in athletes with NFO, as well as in some athletes with OTS, showing sympathetic dominance, considered as a sign of physical or mental fatigue and chronic stress, whereas "Total Autonomic Dystonia" in most of the athletes with OTS (67%) reflects more advanced stage of maladaptation associated with depressed regulatory function of the ANS, both sympathetic, as well as vagal influences. Most frequently NFO and OTS were seen in wrestling, which needs further investigation and regular medical monitoring. Thus, results of the study show progression of autonomic imbalance and depression of regulatory function of the autonomic nervous system in athletes with OTS. The cardiac autonomic imbalance observed in overtrained athletes implies changes in HRV and therefore would consider that heart rate variability may provide useful information in detection of overtraining in athletes and can be a valuable adjacent tool for optimising athlete's training program as well as for timely diagnosis and prevention of progression of NFO/OTS.
Salinity Processes in the Upper Ocean Regional Study (SPURS)
2012-09-04
NASA Physical Oceanography Program Scientist Eric Lindstrom inspects an autonomous wave glider onboard the Woods Hole Oceanographic Institution research vessel Knorr on Tuesday, Sept. 4, 2012, in Woods Hole, Mass. The autonomous gliders will be deployed in the Atlantic Ocean as part of the Salinity Processes in the Upper Ocean Regional Study (SPURS) which is set to sail on Sept. 6. The NASA-sponsored expedition will sail to the North Atlantic's saltiest spot to get a detailed, 3-D picture of how salt content fluctuates in the ocean's upper layers and how these variations are related to shifts in rainfall patterns around the planet. Photo Credit: (NASA/Bill Ingalls)
Liang, Yajun; Wu, Heng; Lei, Rong; Chong, Robert A.; Wei, Yong; Lu, Xin; Tagkopoulos, Ilias; Kung, Sun-Yuan; Yang, Qifeng; Hu, Guohong; Kang, Yibin
2012-01-01
The application of functional genomic analysis of breast cancer metastasis has led to the identification of a growing number of organ-specific metastasis genes, which often function in concert to facilitate different steps of the metastatic cascade. However, the gene regulatory network that controls the expression of these metastasis genes remains largely unknown. Here, we demonstrate a computational approach for the deconvolution of transcriptional networks to discover master regulators of breast cancer bone metastasis. Several known regulators of breast cancer bone metastasis such as Smad4 and HIF1 were identified in our analysis. Experimental validation of the networks revealed BACH1, a basic leucine zipper transcription factor, as the common regulator of several functional metastasis genes, including MMP1 and CXCR4. Ectopic expression of BACH1 enhanced the malignance of breast cancer cells, and conversely, BACH1 knockdown significantly reduced bone metastasis. The expression of BACH1 and its target genes was linked to the higher risk of breast cancer recurrence in patients. This study established BACH1 as the master regulator of breast cancer bone metastasis and provided a paradigm to identify molecular determinants in complex pathological processes. PMID:22875853
Code of Federal Regulations, 2011 CFR
2011-01-01
... ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel Provider Vehicle..., is controlled by, or is under common ownership or control of a person subject to vehicle acquisition... selling at wholesale or retail electricity. Business Unit means a semi-autonomous major grouping of...
Code of Federal Regulations, 2013 CFR
2013-01-01
... ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel Provider Vehicle..., is controlled by, or is under common ownership or control of a person subject to vehicle acquisition... selling at wholesale or retail electricity. Business Unit means a semi-autonomous major grouping of...
Code of Federal Regulations, 2014 CFR
2014-01-01
... ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel Provider Vehicle..., is controlled by, or is under common ownership or control of a person subject to vehicle acquisition... selling at wholesale or retail electricity. Business Unit means a semi-autonomous major grouping of...
Code of Federal Regulations, 2012 CFR
2012-01-01
... ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM Alternative Fuel Provider Vehicle..., is controlled by, or is under common ownership or control of a person subject to vehicle acquisition... selling at wholesale or retail electricity. Business Unit means a semi-autonomous major grouping of...
Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.
Azim, Hamdy A; Abdel-Malek, Raafat; Kassem, Loay
2018-04-01
Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.
Metastasis genetics, epigenetics, and the tumor microenvironment
USDA-ARS?s Scientific Manuscript database
KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...
P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.
Hostettler, Nina; Naggi, Annamaria; Torri, Giangiacomo; Ishai-Michaeli, Riva; Casu, Benito; Vlodavsky, Israel; Borsig, Lubor
2007-11-01
Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we identified modified, nonanticoagulant species of heparin that specifically inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity, or both. We show that selective inhibition of selectin interactions or heparanase with specific heparin derivatives in mouse models of MC-38 colon carcinoma and B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had no effect, in accordance with the virtual absence of heparanase activity in these cells. Heparin derivatives had no further effect on metastasis in mice deficient in P- and L-selectin, indicating that selectins are the primary targets of heparin antimetastatic activity. Selectin-specific and heparanase-specific derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When mice were injected with a derivative containing both heparanase and selectin inhibitory activity, no additional attenuation of metastasis could be observed. Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of both tumor cell types whereas inhibition of heparanase led to reduction of metastasis only in tumor cells producing heparanase.
Ami, Katsunori; Seki, Ryouta; Takasaki, Jun; Amagasa, Hidetoshi; Kamikozuru, Hirotaka; Ganno, Hideaki; Kurokawa, Toshiaki; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Yamada, Yosuke; Kodaka, Fumi; Arai, Kuniyoshi
2012-11-01
At present, fluorouracil and cisplatin combination therapy is the standard chemotherapy against esophageal cancer, but the choice of second-line chemotherapy is controversial. Furthermore, the effect of radiation therapy against lung metastasis from esophageal cancer is unclear. We report a case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy. The patient was a 55-year-old woman who had undergone an operation for esophageal cancer at another hospital. A single right lung metastasis appeared 1 year after the operation. Combined fluorouracil and cisplatin therapy was administrated for 5 courses, but the lung metastasis increased in size. Afterwards, she was admitted to our hospital. We treated her with 14 courses of S-1 and docetaxel combination therapy administered over 13 months. The lung metastasis was decreased for a period. Furthermore, radiofrequency ablation under computed tomography was performed against the lung metastasis re-growth at another hospital. Although the lung metastasis increased in size, no further metastases were detected during the clinical course. The patient was treated with radiotherapy for the lung metastasis re-growth. The tumor had almost disappeared by 10 months after the completion of radiotherapy. Currently, she is receiving palliative care as an outpatient and the lung metastasis has not been evident for 2 years since the completion of radiotherapy.
A qualitative analysis of statements on motivation of applicants for medical school.
Wouters, Anouk; Bakker, Anneke H; van Wijk, Inge J; Croiset, Gerda; Kusurkar, Rashmi A
2014-09-23
Selection committees try to ascertain that motivated students are selected for medical school. Self-determination theory stresses that the type of motivation is more important than the quantity of motivation. Autonomous motivation, compared to controlled motivation, in students leads to better learning outcomes. Applicants can express their motivation in written statements, a selection tool which has been found to elicit heterogeneous responses, hampering the comparison of applicants. This study investigates the content of applicants' statements on motivation for medical school in particular, the possibility to distinguish the type of motivation and the differences between selected and non-selected applicants. A thematic analysis was conducted on written statements on motivation (n = 96), collected as a part of the selection procedure for the graduate entry program for medicine and research at our institution. Themes were identified as motivation-related and motivation-unrelated (additional). The motivation-related themes were further classified as autonomous and controlled types of motivation. Group percentages for each theme were compared between selected and non-selected applicants using Chi-square test and Fisher exact test. Applicants mainly described reasons belonging to autonomous type of motivation and fewer reasons belonging to controlled type of motivation. Additional themes in the statements included previous work experience and academic qualifications, ambitions, expectations and descriptions of the program and profession, personal qualities, and personal history. Applicants used strong words to support their stories. The selected and non-selected applicants did not differ in their types of motivation. Non-selected applicants provided more descriptions of personal history than selected applicants (p < 0.05). The statement on motivation does not appear to distinguish between applicants in selection for medical school. Both selected and non-selected applicants reported mainly autonomous motivation for applying, and included a lot of additional information, which was beyond the scope of what was asked from them. The findings raise a question mark on the validity and reliability of the statement on motivation as a tool for selection. It could however be of added value to enable applicants to tell their story, which they appreciate, and to create awareness of the program, resulting in an informed decision to apply.
Ding, Zhijie; Joy, Marion; Kameneva, Marina V; Roy, Partha
2017-01-01
Metastasis is the leading cause of cancer mortality. Extravasation of cancer cells is a critical step of metastasis. We report a novel proof-of-concept study that investigated whether non-toxic blood-soluble chemical agents capable of rheological modification of the near-vessel-wall blood flow can reduce extravasation of tumor cells and subsequent development of metastasis. Using an experimental metastasis model, we demonstrated that systemic administration of nanomolar concentrations of so-called drag-reducing polymer dramatically impeded extravasation and development of pulmonary metastasis of breast cancer cells in mice. This is the first proof-of-principle study to directly demonstrate physical/rheological, as opposed to chemical, way to prevent cancer cells from extravasation and developing metastasis and, thus, it opens the possibility of a new direction of adjuvant interventional approach in cancer. PMID:28280386
Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi
2016-10-05
Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.
Ruochuan, Zang; Shugeng, Guo; Jie, He; Yousheng, Mao; Qi, Xue; Dali, Wang; Juwei, Mu; Jun, Zhao; Yonggang, Wang; Xiangyang, Liu; Fengwei, Tan; Gefei, Zhao; Qian, Zhang; Moyan, Zhang; Peng, Song
2015-04-01
To explore the relationship between the lymph node metastasis and clinicopathological features in patients with clinical stage T1a non-small cell lung cancer (NSCLC). Clinicopathological data of a total of 418 patients who underwent lobectomy and systematic lymph node dissection were retrospectively analyzed. Logistic regression was used to analyze the relationship between lymph node metastasis and clinicopathological features. Lymph node metastasis was observed in 25 patients. There were 122 patients who were diagnosed as ground glass opacity with no lymph node metastasis. 399 patients had subcarinal dissection, among them 7 patients were found to have lymph node metastasis. Univariate analysis showed that gender, smoking history, diameter of lymph node, ground glass opacity (GGO), differentiation of the tumor and tumor site were the factors affecting lymph node metastasis (all P < 0.05). Logistic regression analysis showed that diameter of lymph node, differentiation of the tumor and the site of lesion were independent risk factors for lymph node metastasis of NSCLC. Tumor in the left lung, poor differentiation, and diameter of lymph nodes ≥ 1 cm on the preoperative CT image are independent risk factors for lymph node metastasis of NSCLC, hence we should pay attention before surgery and systematic lymph node dissection should be done. For patients with poor differentiation and lymph nodes ≥ 1 cm, subcarinal lymph nodes dissection is recommended for the sake of higher possibility of lymph node metastasis. For patients with ground glass opacity ≤ 2 cm, the lymph node metastasis is extremely rare, therefore, selective lymph node dissection is reconmmended.
Predictive values of FAP and HGF for tumor angiogenesis and metastasis in colorectal cancer.
Ma, T H; Gao, C C; Xie, R; Yang, X Z; Dai, W J; Zhang, J L; Yan, W; Wu, S N
2017-01-01
This study aims to explore the correlation of hepatocyte growth factor (HGF) and fibroblast activation protein (FAP) expressions with the angiogenesis and metastasis in colorectal cancer (CRC). The immunohistochemical SABC method was used to detect HGF and FAP expressions in 127 CRC tissues, 51 colorectal polyp tissues and 28 normal tissues. HGF and FAP expressions in liver metastasis were detected using western blot to analyze the correlation of their expressions with lymph node metastasis and liver metastasis. Micro-vessel density (MVD) and clinic-pathologic information of CRC patients were recorded and analyzed. In CRC group, HGF and FAP expressions were greatly higher than those in normal group and colorectal polyps group (P < 0.05). Moreover, the positive rates of HGF and FAP expressions in lymph node metastasis were evidently higher than those in non-lymph node metastasis (P < 0.05). In liver metastasis group, HGF and FAP expressions were obviously higher than non-liver metastasis group (P < 0.05). CRC group had much more MVD in comparison with normal group and colorectal polyps group (P < 0.05).When compared with negative group, MVD was significantly higher than that in CRC tissue with positive HGF and FAP (P < 0.05). Spearman rank correlation analysis showed that HGF and FAP were in positive correlation with MVD (r = 0.542, P < 0.001; r = 0.753, P < 0.001). These results indicate that FAP and HGF play an important role in CRC angiogenesis, and their expression levels are valuable to predict CRC liver metastasis and lymph node metastasis.
S, Vishak; Rohan, Vinayak
2014-06-01
The squamous cell carcinoma (SCC) of the oral tongue is a common cancer in India. Elective lymphadenectomy is generally performed in all patients with T2-T4 tumors. In this study we have tried to analyze the pattern and risk factors associated with lymph node metastasis in T1 tongue cancers. A retrospective review of the records of 57 patients undergoing surgery for treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The clinicopatological features of the tumor, pattern of nodal metastasis and the risk factors associated with lymph node metastasis were studied. Totally 57 patients with T1 tumor underwent excision of the primary and modified neck dissection (MND). Lymph node metastasis was found in 36.8 % of the patients. Level I to Level II was the commonest site of metastasis. Skip metastasis at level III and IV was found in 8.5 % of the patients and isolated skip metastasis at level IV in 1.5 % of the patients. The risk factors associated with the lymph node metastasis on univariete analysis were; higher grade, tumor size >1 cm and tumor thickness >3 mm. On multivariate analysis only the tumor thickness was found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59). T1 sqamous cell carcinoma of tongue is associated with a high incidence of lymph node metastasis. Elective neck dissection should be considered in all patients with tumors more than 3 mm in thickness.
Autonomous Scheduling Requirements for Agile Cubesat Constellations in Earth Observation
NASA Astrophysics Data System (ADS)
Nag, S.; Li, A. S. X.; Kumar, S.
2017-12-01
Distributed Space Missions such as formation flight and constellations, are being recognized as important Earth Observation solutions to increase measurement samples over space and time. Cubesats are increasing in size (27U, 40 kg) with increasing capabilities to host imager payloads. Given the precise attitude control systems emerging commercially, Cubesats now have the ability to slew and capture images within short notice. Prior literature has demonstrated a modular framework that combines orbital mechanics, attitude control and scheduling optimization to plan the time-varying orientation of agile Cubesats in a constellation such that they maximize the number of observed images, within the constraints of hardware specs. Schedule optimization is performed on the ground autonomously, using dynamic programming with two levels of heuristics, verified and improved upon using mixed integer linear programming. Our algorithm-in-the-loop simulation applied to Landsat's use case, captured up to 161% more Landsat images than nadir-pointing sensors with the same field of view, on a 2-satellite constellation over a 12-hour simulation. In this paper, we will derive the requirements for the above algorithm to run onboard small satellites such that the constellation can make time-sensitive decisions to slew and capture images autonomously, without ground support. We will apply the above autonomous algorithm to a time critical use case - monitoring of precipitation and subsequent effects on floods, landslides and soil moisture, as quantified by the NASA Unified Weather Research and Forecasting Model. Since the latency between these event occurrences is quite low, they make a strong case for autonomous decisions among satellites in a constellation. The algorithm can be implemented in the Plan Execution Interchange Language - NASA's open source technology for automation, used to operate the International Space Station and LADEE's in flight software - enabling a controller-in-the-loop demonstration. The autonomy software can then be integrated with NASA's open source Core Flight Software, ported onto a Raspberry Pi 3.0 for a software-in-the-loop demonstration. Future use cases can be time critical events such as cloud movement, storms or other disasters, and in conjunction with other platforms in a Sensor Web.
Targeting Neuromimicry in Prostate Cancer Metastasis
2016-10-01
CONTRACTING ORGANIZATION: Cedars-Sinai Medical Center Los Angeles, CA 90048 REPORT DATE: October 2016 TYPE OF REPORT: Annual PREPARED FOR: U.S...ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Cedars-Sinai Medical Center 8700 Beverly Blvd Los Angeles, CA 90048-1804 9...by activation of axon guidance genes Jason Boyang Wu, Haiyen E. Zhau, and Leland W.K. Chung Uro -Oncology Research Program, Department of
Further development and flight test of an autonomous precision landing system using a parafoil
NASA Technical Reports Server (NTRS)
Murray, James E.; Sim, Alex G.; Neufeld, David C.; Rennich, Patrick K.; Norris, Stephen R.; Hughes, Wesley S.
1994-01-01
NASA Dryden Flight Research Center and NASA Johnson Space Center are jointly conducting a phased program to determine the feasibility of the autonomous recovery of a spacecraft using a ram-air parafoil system for the final stages of entry from space to a precision landing. The feasibility is being studied using a flight model of a spacecraft in the generic shape of a flattened biconic that weighs approximately 120 lb and is flown under a commercially available ram-air parafoil. Key components of the vehicle include the global positioning system (GPS) guidance for navigation, a flight control computer, an electronic compass, a yaw rate gyro, and an onboard data recorder. A flight test program is being used to develop and refine the vehicle. The primary flight goal is to demonstrate autonomous flight from an altitude of 3,000 m (10,000 ft) with a lateral offset of 1.6 km (1.0 mi) to a precision soft landing. This paper summarizes the progress to date. Much of the navigation system has been tested, including a heading tracker that was developed using parameter estimation techniques and a complementary filter. The autoland portion of the autopilot is still in development. The feasibility of conducting the flare maneuver without servoactuators was investigated as a means of significantly reducing the servoactuator rate and load requirements.
Cutaneous metastasis of bilateral renal cell carcinoma.
Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin
2013-01-01
Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.
Paediatric cardiopulmonary resuscitation training program in Latin-America: the RIBEPCI experience.
López-Herce, Jesús; Matamoros, Martha M; Moya, Luis; Almonte, Enma; Coronel, Diana; Urbano, Javier; Carrillo, Ángel; Del Castillo, Jimena; Mencía, Santiago; Moral, Ramón; Ordoñez, Flora; Sánchez, Carlos; Lagos, Lina; Johnson, María; Mendoza, Ovidio; Rodriguez, Sandra
2017-09-12
To describe the design and to present the results of a paediatric and neonatal cardiopulmonary resuscitation (CPR) training program adapted to Latin-America. A paediatric CPR coordinated training project was set up in several Latin-American countries with the instructional and scientific support of the Spanish Group for Paediatric and Neonatal CPR. The program was divided into four phases: CPR training and preparation of instructors; training for instructors; supervised teaching; and independent teaching. Instructors from each country participated in the development of the next group in the following country. Paediatric Basic Life Support (BLS), Paediatric Intermediate (ILS) and Paediatric Advanced (ALS) courses were organized in each country adapted to local characteristics. Five Paediatric Resuscitation groups were created sequentially in Honduras (2), Guatemala, Dominican Republican and Mexico. During 5 years, 6 instructors courses (94 students), 64 Paediatric BLS Courses (1409 students), 29 Paediatrics ILS courses (626 students) and 89 Paediatric ALS courses (1804 students) were given. At the end of the program all five groups are autonomous and organize their own instructor courses. Training of autonomous Paediatric CPR groups with the collaboration and scientific assessment of an expert group is a good model program to develop Paediatric CPR training in low- and middle income countries. Participation of groups of different countries in the educational activities is an important method to establish a cooperation network.
Isolated gastrointestinal metastasis of breast carcinoma: a case report.
Titi, M A; Anabtawi, A; Newland, A D
2010-01-01
Purpose. Gastrointestinal tract is one of the rare locations for breast cancer metastasis. This paper shows such metastasis may occur even in the absence of breast metastasis in other more common locations. Case Report. A 64-year old female was admitted to the hospital with abdominal discomfort and diarrhea. She had breast carcinoma treated 7 years previously with normal follow-up since. Colonoscopy showed hepatic flexure thickening that was confirmed to be breast metastasis. Staging investigations showed upper and lower gastrointestinal tract metastasis with negative findings elsewhere. Conclusion. Although more common causes for gastrointestinal symptoms should be excluded, however, a high index of suspicion of metastatic breast cancer is needed when such patients develop gastrointestinal symptoms.
Breast cancer lung metastasis: Molecular biology and therapeutic implications.
Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang
2018-03-26
Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.
DOT National Transportation Integrated Search
2017-12-01
Visions of self-driving vehicles abound in popular science and entertainment. Many programs are at work to make a reality catch of this imagination. Vehicle automation has progressed rapidly in recent years, from simple driver assistance technologies...
Status of DoD Robotic Programs
1985-03-01
planning or adhere to previously planned routes. 0 Control. Controls are micro electronics based which provide means of autonomous action directly...KEY No: I 11 1181 1431 OROJECT Titloi ISMART TERRAIN ANALYSIS FOR ROBOTIC SYSTEMS (STARS) PROJECT Not I I CLASSIFICATION: IUCI TASK Titles IAUTOMATIC
Astrobiology Science and Technology: A Path to Future Discovery
NASA Technical Reports Server (NTRS)
Meyer, M. A.; Lavaery, D. B.
2001-01-01
The Astrobiology Program is described. However, science-driven robotic exploration of extreme environments is needed for a new era of planetary exploration requiring biologically relevant instrumentation and extensive, autonomous operations on planetary surfaces. Additional information is contained in the original extended abstract.
Kim, Moinay; Cheok, Stephanie; Chung, Lawrance K.; Ung, Nolan; Thill, Kimberly; Voth, Brittany; Kwon, Do Hoon; Kim, Jeong Hoon; Kim, Chang Jin; Tenn, Stephen; Lee, Percy
2015-01-01
Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes. PMID:25977901
Epigenetic regulator RBP2 is critical for breast cancer progression and metastasis
Cao, Jian; Liu, Zongzhi; Cheung, William K.C.; Zhao, Minghui; Chen, Sophia Y.; Chan, Siew Wee; Booth, Carmen J.; Nguyen, Don X.; Yan, Qin
2014-01-01
Summary Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that epigenetic aberrations contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene expression datasets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes. In addition, RBP2 loss suppresses tumor formation in the MMTV-neu transgenic mice. These results suggest that therapeutically targeting RBP2 is a potential strategy to inhibit tumor progression and metastasis. PMID:24582965
Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer
2000-07-01
September 29 Identifying and characterizing human metastasis-suppressor genes. Novartis Pharma , May WELCH, Danny R, Ph.D...Growth and Differentiation Chemica -Biological Interactions CRC Press - Reviews European Journal of Cancer and Clinical Oncology Journal of...September 29 Identifying and characterizing human metastasis-suppressor genes. Novartis Pharma , May 27 Regulation of Metastasis in Human Cancers
An Atypical Metastasis of Follicular-Type Adenocarcinoma of the Thyroid Gland to Thumb
Huri, Gazi
2011-01-01
Bone metastasis in the hand is rare. The etiology of metastatic hand cancers is different from other bones. Bronchogenic carcinoma is the most common primary tumor metastasis to hand. In this paper a rare case of thumb metastasis from “follicular-type carcinoma” of the thyroid is presented. PMID:23198224
Hematogenous Renal Cell Carcinoma Metastasis in the Postoperative Temporal Bone
Konishi, Masaya; Suzuki, Kensuke; Iwai, Hiroshi
2017-01-01
Metastatic renal cell carcinoma (RCC) involving the temporal bone is a rare entity. It is usually asymptomatic and misdiagnosis as acute otitis media, mastoiditis, and Ramsay-Hunt syndrome in early onset is not uncommon. We report a case of RCC metastasis to the postoperative temporal bone in the middle of molecular targeted therapy. A 60-year-old man presented left facial palsy with severe retro-auricular pain and he also underwent left middle ear surgery for cholesteatoma more than 30 years before and had been aware of discontinuous otorrhea; therefore, initially we speculated that facial palsy was derived from recurrent cholesteatoma or Ramsay-Hunt syndrome. Exploratory tympanotomy revealed RCC metastasis and postoperative MR indicated hematogenous metastasis. To the best of our knowledge, no report was obtained on temporal bone metastasis in the middle of chemotherapy or hematogenous metastasis in the postoperative middle ear. Metastasis in the temporal bone is still a possible pathological condition despite the development of present cancer therapy. Besides, this case indicates that hematogenous metastasis can occur in the postoperative state of the temporal bone. PMID:28611633
Contractor, Tanupriya; Kobayashi, Shinta; da Silva, Edaise; Clausen, Richard; Chan, Chang; Vosburgh, Evan; Tang, Laura H; Levine, Arnold J; Harris, Chris R
2016-05-24
In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors.
Supervisory autonomous local-remote control system design: Near-term and far-term applications
NASA Technical Reports Server (NTRS)
Zimmerman, Wayne; Backes, Paul
1993-01-01
The JPL Supervisory Telerobotics Laboratory (STELER) has developed a unique local-remote robot control architecture which enables management of intermittent bus latencies and communication delays such as those expected for ground-remote operation of Space Station robotic systems via the TDRSS communication platform. At the local site, the operator updates the work site world model using stereo video feedback and a model overlay/fitting algorithm which outputs the location and orientation of the object in free space. That information is relayed to the robot User Macro Interface (UMI) to enable programming of the robot control macros. The operator can then employ either manual teleoperation, shared control, or supervised autonomous control to manipulate the object under any degree of time-delay. The remote site performs the closed loop force/torque control, task monitoring, and reflex action. This paper describes the STELER local-remote robot control system, and further describes the near-term planned Space Station applications, along with potential far-term applications such as telescience, autonomous docking, and Lunar/Mars rovers.
An architectural approach to create self organizing control systems for practical autonomous robots
NASA Technical Reports Server (NTRS)
Greiner, Helen
1991-01-01
For practical industrial applications, the development of trainable robots is an important and immediate objective. Therefore, the developing of flexible intelligence directly applicable to training is emphasized. It is generally agreed upon by the AI community that the fusion of expert systems, neural networks, and conventionally programmed modules (e.g., a trajectory generator) is promising in the quest for autonomous robotic intelligence. Autonomous robot development is hindered by integration and architectural problems. Some obstacles towards the construction of more general robot control systems are as follows: (1) Growth problem; (2) Software generation; (3) Interaction with environment; (4) Reliability; and (5) Resource limitation. Neural networks can be successfully applied to some of these problems. However, current implementations of neural networks are hampered by the resource limitation problem and must be trained extensively to produce computationally accurate output. A generalization of conventional neural nets is proposed, and an architecture is offered in an attempt to address the above problems.
Autonomous Payload Operations Onboard the International Space Station
NASA Technical Reports Server (NTRS)
Stetson, Howard K.; Deitsch, David K.; Cruzen, Craig A.; Haddock, Angie T.
2007-01-01
Operating the International Space Station (ISS) involves many complex crew tended, ground operated and combined systems. Over the life of the ISS program, it has become evident that by having automated and autonomous systems on board, more can be accomplished and at the same time reduce the workload of the crew and ground operators. Engineers at the National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center in Huntsville Alabama, working in collaboration with The Charles Stark Draper Laboratory have developed an autonomous software system that uses the Timeliner User Interface Language and expert logic to continuously monitor ISS payload systems, issue commands and signal ground operators as required. This paper describes the development history of the system, its concept of operation and components. The paper also discusses the testing process as well as the facilities used to develop the system. The paper concludes with a description of future enhancement plans for use on the ISS as well as potential applications to Lunar and Mars exploration systems.
Inhibitory effect of magnolol on tumour metastasis in mice.
Ikeda, Koji; Sakai, Yoshimichi; Nagase, Hisamitsu
2003-09-01
It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol significantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation significantly suppressed lung metastasis and primary tumour growth. In addition, magnolol significantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion. Copyright 2003 John Wiley & Sons, Ltd.
Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi
2017-06-01
Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.
Biomechanical effects of metastasis in the osteoporotic lumbar spine: A Finite Element Analysis.
Salvatore, Giuseppe; Berton, Alessandra; Giambini, Hugo; Ciuffreda, Mauro; Florio, Pino; Longo, Umile Giuseppe; Denaro, Vincenzo; Thoreson, Andrew; An, Kai-Nan
2018-02-05
Cancer patients are likely to undergo osteoporosis as consequence of hormone manipulation and/or chemotherapy. Little is known about possible increased risk of fracture in this population. The aim of this study was to describe the biomechanical effect of a metastatic lesion in an osteoporotic lumbar spine model. A finite element model of two spinal motion segments (L3-L5) was extracted from a previously developed L3-Sacrum model and used to analyze the effect of metastasis size and bone mineral density (BMD) on Vertebral bulge (VB) and Vertebral height (VH). VB and VH represent respectively radial and axial displacement and they have been correlated to burst fracture. A total of 6 scenarios were evaluated combining three metastasis sizes (no metastasis, 15% and 30% of the vertebral body) and two BMD conditions (normal BMD and osteoporosis). 15% metastasis increased VB and VH by 178% and 248%, respectively in normal BMD model; while VB and VH increased by 134% and 174% in osteoporotic model. 30% metastasis increased VB and VH by 88% and 109%, respectively, when compared to 15% metastasis in normal BMD model; while VB and VH increased by 59% and 74% in osteoporotic model. A metastasis in the osteoporotic lumbar spine always leads to a higher risk of vertebral fracture. This risk increases with the size of the metastasis. Unexpectedly, an increment in metastasis size in the normal BMD spine produces a greater impact on vertebral stability compared to the osteoporotic spine.
Clinical Characteristics of Patients With Renal Cell Carcinoma and Metastasis to the Thyroid Gland.
Jackson, Gregory; Fino, Nora; Bitting, Rhonda L
2017-01-01
Renal cell carcinoma (RCC) is the most common malignancy to metastasize to the thyroid gland. The aims of this study are as follows: (1) to analyze the clinical characteristics of patients with thyroid involvement of RCC and (2) in patients with RCC thyroid metastasis, to determine whether RCC metastasis to glandular organs only portends a better prognosis compared with other patterns of RCC metastasis. Patients from Wake Forest Baptist Medical Center (WFBMC) diagnosed with thyroid metastasis from RCC were identified and medical records retrospectively examined. A systematic review of the literature for cases of RCC involving the thyroid gland was also performed. The clinical characteristics of the institutional cohort and the cases from the literature review were compared. Descriptive statistical analysis was performed, and overall survival (OS) was summarized using Kaplan-Meier methods. The median OS for the WFBMC cohort was 56.4 months. In the literature review cohort, OS of patients with RCC thyroid metastasis was 213.6 months, and there was no statistically significant survival difference based on the site of metastasis. Median survival after thyroid metastasis from RCC for the WFBMC and literature cohort was 21.6 and 45.6 months, respectively. Metastatic RCC should be included in the differential of a new thyroid mass. Treatment directed at the thyroid metastasis results in prolonged survival in some cases. Further analysis into the genomic differences and mechanisms of thyroid metastasis is warranted.
Expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer.
Mikami, Koji; Hirano, Yukiko; Futami, Kitaro; Maekawa, Takafumi
2017-07-18
Mixed-type early gastric cancer (differentiated and undifferentiated components) incurs a higher risk of lymph node metastasis than pure-type early gastric cancer (only differentiated or only undifferentiated components). Therefore, we investigated the expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer in order to establish the most appropriate treatment for mixed-type cancer. We retrospectively analyzed 279 consecutive patients with submucosal invasive gastric cancer who underwent curative gastrectomy for gastric cancer between 1996 and 2015. We classified the patients into the mixed-type and pure-type groups according to histologic examination and evaluated the expansion of lymph node metastasis. The rate of lymph node metastasis was 23.7% (66/279) in the total patients, 36.4% (36/99) in the mixed-type group, and 16.6% (30/180) in the pure-type group. The significant independent risk factors for lymph node metastasis were tumor size ≥2.0 cm (P = 0.014), mixed-type gastric cancer (P < 0.001), and lymphatic invasion (P < 0.001). Lymphatic invasion and lymph node metastasis had a strong relationship in mixed-type group. The rates of no. 7 lymph node metastasis in the total patients and mixed-type group were 2.9% (8/279) and 5.1% (5/99), respectively; the rates of no. 8a lymph node metastasis were 1.4% (4/279) and 4.0% (4/99), respectively. Mixed histological type is an independent risk factor for lymph node metastasis. Lymph node metastasis in mixed-type gastric cancer involves expansion to the no. 7 and no. 8a lymph nodes. Therefore, lymphadenectomy for mixed-type submucosal invasive gastric cancer requires D1+ or D2 dissection. Copyright © 2017. Published by Elsevier Taiwan.
Oh, Dongryul; Ahn, Yong Chan; Park, Hee Chul; Lim, Do Hoon; Noh, Jae Myoung; Cho, Won Kyung; Pyo, Hongryull
2017-05-30
This study aimed to investigate the prognostic impact of supraclavicular lymph node (SCN) metastasis in patients who were treated with definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer (NSCLC). The 2- and 5-year overall survival (OS) rates were 57.3% and 35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN metastasis, respectively. The median OS was 34 months in both groups. There was no significant difference in OS between the two groups (p = 0.679). The 2- and 5-year progression-free survival (PFS) rates were 24.1% and 12.6% in patients without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis, respectively. Patients without SCN metastasis had slightly longer median PFS (10 months vs. 8 months), but the difference was not statistically significant (p = 0.223). In multivariate analysis, SCN metastasis was not a significant factor for OS (p = 0.391) and PFS (p = 0.149). This retrospective analysis included 204 consecutive patients who were treated with chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients (58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease: mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one (1.2%). The patients were divided into two groups according to SCN metastasis. SCN metastasis does not compromise treatment outcomes compared to other mediastinal metastasis in the setting of definitive chemoradiotherapy.
Vosoughi, Elham; Lee, Jee Min; Miller, James R; Nosrati, Mehdi; Minor, David R; Abendroth, Roy; Lee, John W; Andrews, Brian T; Leng, Lewis Z; Wu, Max; Leong, Stanley P; Kashani-Sabet, Mohammed; Kim, Kevin B
2018-04-27
Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.
Kim, Soo-Yeon; Lee, Eunjung; Nam, Se Jin; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Han, Kyung Hwa; Kwak, Jin Young
2017-01-01
This retrospective study aimed to evaluate whether ultrasound texture analysis is useful to predict lymph node metastasis in patients with papillary thyroid microcarcinoma (PTMC). This study was approved by the Institutional Review Board, and the need to obtain informed consent was waived. Between May and July 2013, 361 patients (mean age, 43.8 ± 11.3 years; range, 16-72 years) who underwent staging ultrasound (US) and subsequent thyroidectomy for conventional PTMC ≤ 10 mm between May and July 2013 were included. Each PTMC was manually segmented and its histogram parameters (Mean, Standard deviation, Skewness, Kurtosis, and Entropy) were extracted with Matlab software. The mean values of histogram parameters and clinical and US features were compared according to lymph node metastasis using the independent t-test and Chi-square test. Multivariate logistic regression analysis was performed to identify the independent factors associated with lymph node metastasis. Tumors with lymph node metastasis (n = 117) had significantly higher entropy compared to those without lymph node metastasis (n = 244) (mean±standard deviation, 6.268±0.407 vs. 6.171±.0.405; P = .035). No additional histogram parameters showed differences in mean values according to lymph node metastasis. Entropy was not independently associated with lymph node metastasis on multivariate logistic regression analysis (Odds ratio, 0.977 [95% confidence interval (CI), 0.482-1.980]; P = .949). Younger age (Odds ratio, 0.962 [95% CI, 0.940-0.984]; P = .001) and lymph node metastasis on US (Odds ratio, 7.325 [95% CI, 3.573-15.020]; P < .001) were independently associated with lymph node metastasis. Texture analysis was not useful in predicting lymph node metastasis in patients with PTMC.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu
Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonlymore » used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.« less
Active Tobacco Smoking and Distant Metastasis in Patients With Oropharyngeal Cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
McBride, Sean M.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Ali, Nawal N.
Purpose: Distant metastasis is the site of first relapse in approximately one-third of patients with locally advanced oropharyngeal carcinoma, irrespective of human papillomavirus status. Yet the risk factors associated with distant metastasis are not well characterized. We sought to characterize the relationship between smoking status and distant metastasis. Methods and Materials: We evaluated the association between tobacco smoking status and distant metastasis in a retrospective cohort study of 132 patients who underwent definitive radiation therapy and chemotherapy for Stage III-IVA/B oropharyngeal cancer. Information on tobacco smoking was prospectively collected by patient questionnaires and physician notes at the time of diagnosis.more » Thirty-three percent of the patients were nonsmokers, 51% were former smokers, 16% were active smokers. The cumulative lifetime tobacco smoking in pack-years was 20 (range, 0-150). Results: With a median follow-up time of 52 months, the overall rate of distant metastasis at 4 years was 8%. Distant metastasis was the most common first site of relapse, occurring in 56% of the patients with recurrences. Active smokers had higher rates of distant metastasis than non-active smokers (including never- and former smokers; 31% vs. 4%, p < 0.001) and former smokers (31% vs. 3%, p < 0.001). There was no statistically significant difference in the risk of distant metastasis for patients with lifetime cumulative pack-years >20 and {<=}20 (10% vs. 4%, p = 0.19). In univariate analysis, active smoking (p = 0.0004) and N category (p = 0.009) were predictive of increased risk of distant metastasis. In multivariate analysis, active smoking was the most significant predictive factor for increased risk of distant metastasis (hazard ratio, 12.7, p < 0.0001). Conclusions: This study identified a strong association between active smoking and distant metastasis in patients with oropharyngeal cancer.« less
Bae, Mi Kyung; Yu, Woo Sik; Byun, Go Eun; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Chung, Kyung Young
2015-05-01
This study aimed to determine prognostic factors associated with postrecurrence survival in cases with postoperative brain metastasis but with no extracranial metastasis in non-small cell lung cancer (NSCLC). Between 1992 and 2012, a total of 2832 patients underwent surgical resection for NSCLC. Among those, 86 patients had postoperative brain metastasis as the initial recurrence. Those patients were retrospectively reviewed. The median follow-up time after the initial lung resection was 24.0 months (range, 2.0-126.0 months). The median overall survival after initial lung cancer resection was 25.0 months and the median overall postrecurrence survival was 11 months. An initial lesion of adenocarcinoma (hazard ratio, 0.548; 95% confidence interval, 0.318 to 0.946; p=0.031), non-pneumonectomy, and a disease-free interval longer than 10.0 months (hazard ratio, 0.565; 95% confidence interval, 0.321-0.995; p=0.048) from the initial lung resection to the diagnosis of brain metastasis positively related to a good postrecurrence survival. Solitary brain metastasis and a size of less than 3 cm for the largest brain lesion were also positive factors for postrecurrence survival. Systemic chemotherapy for brain metastasis (hazard ratio, 0.356; 95% confidence interval, 0.189-0.670; p=0.001) and local treatment of surgery and/or stereotactic radiosurgery (SRS) for brain lesions (hazard ratio, 0.321; 95% confidence interval, 0.138-0.747; p=0.008) were positive factors for better postrecurrence survival. In patients with brain metastasis after resection for NSCLC with no extracranial metastasis, adenocarcinoma histologic type, longer disease-free interval, systemic chemotherapy for brain metastasis and local treatment of surgery and/or SRS for brain metastasis are independent positive prognostic factors for postrecurrence survival. Copyright © 2015. Published by Elsevier Ireland Ltd.
Panax notoginseng saponins (PNS) inhibits breast cancer metastasis.
Wang, Peiwei; Cui, Jingang; Du, Xiaoye; Yang, Qinbo; Jia, Chenglin; Xiong, Minqi; Yu, Xintong; Li, Li; Wang, Wenjian; Chen, Yu; Zhang, Teng
2014-07-03
Panax notoginseng (Burkill) F.H. Chen (Araliaceae) has been extensively used as a therapeutic agent to treat a variety of diseases. Panax notoginseng saponins (PNS) consist of major therapeutically active components of Panax notoginseng. PNS inhibit the growth of a variety of tumor cells in vitro and in vivo. The aim of the study is to investigate the effects and underlying mechanisms of PNS on breast cancer metastasis. 4T1 cell, a highly metastatic mouse breast carcinoma cell line, was utilized for in vitro and in vivo assays. In vitro assays were first performed to examine the effects of PNS on 4T1 cell viability, migration and invasion, respectively. Real-time PCR analyses were also performed to examine the effects of PNS on the expression of genes associated with tumor metastasis. The effect of PNS on 4T1 tumor cell metastasis was further assessed in spontaneous and experimental metastasis models in vivo. PNS treatment exhibited a dose-dependent effect on impairing 4T1 cell viability in vitro. However, when examined at a lower dose that did not affect cell viability, the migration and invasion of 4T1 cell was remarkably inhibited in vitro. Meanwhile, PNS treatment led to upregulated expression of genes known to inhibit metastasis and downregulated expression of genes promoting metastasis in cultured 4T1 cells. These results suggested a selective effect of PNS on 4T1 migration and invasion. This hypothesis was further addressed in 4T1 metastasis models in vivo. The results showed that the lung metastasis was significantly inhibited by PNS treatment in both spontaneous and experimental metastasis models. Taken together, our results demonstrated an inhibitory effect of PNS on 4T1 tumor metastasis, warranting further evaluation of PNS as a therapeutic agent for treating breast cancer metastasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Global Precipitation Measurement (GPM) Orbit Design and Autonomous Maneuvers
NASA Technical Reports Server (NTRS)
Folta, David; Mendelsohn, Chad; Mailhe, Laurie
2003-01-01
The NASA Goddard Space Flight Center's Global Precipitation Measurement (GPM) mission must meet the challenge of measuring worldwide precipitation every three hours. The GPM core spacecraft, part of a constellation, will be required to maintain a circular orbit in a high drag environment at a near-critical inclination. Analysis shows that a mean orbit altitude of 407 km is necessary to prevent ground track repeating. Combined with goals to minimize maneuver operation impacts to science data collection and to enable reasonable long-term orbit predictions, the GPM project has decided to fly the GSFC autonomous maneuver system, AutoCon(TM). This system is a follow-up version of the highly successful New Millennium Program technology flown onboard the Earth Observing-1 formation flying mission. This paper presents the driving science requirements and goals of the GPM mission and shows how they will be met. Selection of the mean semi-major axis, eccentricity, and the AV budget for several ballistic properties are presented. The architecture of the autonomous maneuvering system to meet the goals and requirements is presented along with simulations using GPM parameters. Additionally, the use of the GPM autonomous system to mitigate possible collision avoidance and to aid other spacecraft systems during navigation outages is explored.
SOLON: An autonomous vehicle mission planner
NASA Technical Reports Server (NTRS)
Dudziak, M. J.
1987-01-01
The State-Operator Logic Machine (SOLON) Planner provides an architecture for effective real-time planning and replanning for an autonomous vehicle. The highlights of the system, which distinguish it from other AI-based planners that have been designed previously, are its hybrid application of state-driven control architecture and the use of both schematic representations and logic programming for the management of its knowledge base. SOLON is designed to provide multiple levels of planning for a single autonomous vehicle which is supplied with a skeletal, partially-specified mission plan at the outset of the vehicle's operations. This mission plan consists of a set of objectives, each of which will be decomposable by the planner into tasks. These tasks are themselves comparatively complex sets of actions which are executable by a conventional real-time control system which does not perform planning but which is capable of making adjustments or modifications to the provided tasks according to constraints and tolerances provided by the Planner. The current implementation of the SOLON is in the form of a real-time simulation of the Planner module of an Intelligent Vehicle Controller (IVC) on-board an autonomous underwater vehicle (AUV). The simulation is embedded within a larger simulator environment known as ICDS (Intelligent Controller Development System) operating on a Symbolics 3645/75 computer.
Solianik, Rima; Sujeta, Artūras; Terentjevienė, Asta; Skurvydas, Albertas
2016-01-01
Objectives. The acute fasting-induced cardiovascular autonomic response and its effect on cognition and mood remain debatable. Thus, the main purpose of this study was to estimate the effect of a 48 h, zero-calorie diet on autonomic function, brain activity, cognition, and mood in amateur weight lifters. Methods. Nine participants completed a 48 h, zero-calorie diet program. Cardiovascular autonomic function, resting frontal brain activity, cognitive performance, and mood were evaluated before and after fasting. Results. Fasting decreased ( p < 0.05) weight, heart rate, and systolic blood pressure, whereas no changes were evident regarding any of the measured heart rate variability indices. Fasting decreased ( p < 0.05) the concentration of oxygenated hemoglobin and improved ( p < 0.05) mental flexibility and shifting set, whereas no changes were observed in working memory, visuospatial discrimination, and spatial orientation ability. Fasting also increased ( p < 0.05) anger, whereas other mood states were not affected by it. Conclusions. 48 h fasting resulted in higher parasympathetic activity and decreased resting frontal brain activity, increased anger, and improved prefrontal-cortex-related cognitive functions, such as mental flexibility and set shifting, in amateur weight lifters. In contrast, hippocampus-related cognitive functions were not affected by it.
Skurvydas, Albertas
2016-01-01
Objectives. The acute fasting-induced cardiovascular autonomic response and its effect on cognition and mood remain debatable. Thus, the main purpose of this study was to estimate the effect of a 48 h, zero-calorie diet on autonomic function, brain activity, cognition, and mood in amateur weight lifters. Methods. Nine participants completed a 48 h, zero-calorie diet program. Cardiovascular autonomic function, resting frontal brain activity, cognitive performance, and mood were evaluated before and after fasting. Results. Fasting decreased (p < 0.05) weight, heart rate, and systolic blood pressure, whereas no changes were evident regarding any of the measured heart rate variability indices. Fasting decreased (p < 0.05) the concentration of oxygenated hemoglobin and improved (p < 0.05) mental flexibility and shifting set, whereas no changes were observed in working memory, visuospatial discrimination, and spatial orientation ability. Fasting also increased (p < 0.05) anger, whereas other mood states were not affected by it. Conclusions. 48 h fasting resulted in higher parasympathetic activity and decreased resting frontal brain activity, increased anger, and improved prefrontal-cortex-related cognitive functions, such as mental flexibility and set shifting, in amateur weight lifters. In contrast, hippocampus-related cognitive functions were not affected by it. PMID:28025637
Funazo, Tomoko; Morita, Kyohei; Ikegami, Naoya; Konishi, Chisato; Nakao, Satoshi; Ariyasu, Ryo; Taki, Masato; Nakagawa, Kazuhiko; Hwang, Moon Hee; Yoshimura, Chie; Wakayama, Toshiaki; Nishizaka, Yasuo
2017-09-01
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy. Alectinib may be the best treatment for choroidal metastasis in patients harboring an ALK translocation because of its favorable side effect profile involving visual disturbances.
Garrido Elustondo, Sofía; Sánchez Padilla, Elisabeth; Ramírez Alesón, Victoria; González Hernández, Ma José; González Navarro, Andrés; López Gómez, Carlos
2008-01-01
Mammogram screening is the most effective method for the early detection of breast cancer. The objective of this study is to evaluate the degree of knowledge, the opinion and the participation in the early breast cancer detection program on the part of the family physicians of the Autonomous Community of Madrid. The population studied was comprised of family physicians from Madrid Health District Seven. An anonymous, self-administered questionnaire comprised of 30 questions grouped into physicians characteristics and opinion concerning the early breast cancer detection programs. A total of 46% of the physicians replied. A total of 94% of the physicians believed that it is their duty to inform their patients concerning preventive activities, including breast cancer screening, and 95% believed their advice to be useful for convincing women to have a mammogram. A total of 72% believed information to be lacking on this program. During the time when mammograms are being taken at their centres, 24% of the physicians surveyed always or almost always ask the women if they have any doubts or would like further information, 43% having set up appointments for them and 95% advising them to have a mammogram taken. The family physicians have a good opinion of the early breast cancer detection program and feel their advice to be effective for improving the participation in the program. They report lack of information and inform women about the program to only a small degree.
[Programs of early detection of breast cancer and access of mammography in Spain].
Luengo, S; Azcona, B; Lázaro, P; Madero, R
1997-05-24
We studied availability to mammography among Spanish women aged 40 to 70 years, variation in use of the mammography by autonomous community, and the situation and importance of breast cancer screening programs among other factors, in the access to mammography. A cross-sectional population survey was conducted in 1994 in a sample of 3,218 women. A questionnaire was used to collect data on the variable access (receipt of at least one mammogram in the last 2 years) as well as different access-related variables. Information on breast cancer screening programs was collected by contacting the responsible institutions. We considered that a program had total coverage if it included all the municipalities in the province and partial if it did not include all municipalities. Twenty-eight percent of women had performed a mammogram. This proportion varied among autonomous communities (AACC) from 11.5 to 73.8%. Breast cancer screening programs existed in 8 AACC. The multivariant analysis revealed an association between access to mammography and the existence of a screening program, especially when the later had total coverage (OR = 7.64; 95% CI = 5.24-11.10). An association was also found between access to mammography and physician-related factors, place of residence and attitudes of women toward mammography. Less than one third of women aged 40-70 have performed a mammography in the last 2 years, and this proportion varies among AACC. Gynecologist visits and the existence of breast cancer screening programs are fundamental factors in the access to mammography in Spain.
Robot Training Through Incremental Learning
2011-04-18
Turing Associates, Ann Arbor, MI 48103 ABSTRACT The real world is too complex and variable to directly program an autonomous ground robot’s...11 th Conf. Uncertainty in Artificial Intelligence, 338-45 (1995). [6] J. Cleary and L. Trigg, “K*: An Instance-based learner using an entropic
Marshall, Thomas; Champagne-Langabeer, Tiffiany; Castelli, Darla; Hoelscher, Deanna
2017-12-01
To present research models based on artificial intelligence and discuss the concept of cognitive computing and eScience as disruptive factors in health and life science research methodologies. The paper identifies big data as a catalyst to innovation and the development of artificial intelligence, presents a framework for computer-supported human problem solving and describes a transformation of research support models. This framework includes traditional computer support; federated cognition using machine learning and cognitive agents to augment human intelligence; and a semi-autonomous/autonomous cognitive model, based on deep machine learning, which supports eScience. The paper provides a forward view of the impact of artificial intelligence on our human-computer support and research methods in health and life science research. By augmenting or amplifying human task performance with artificial intelligence, cognitive computing and eScience research models are discussed as novel and innovative systems for developing more effective adaptive obesity intervention programs.
Mott, Antonio R; Neish, Steven R; Challman, Melissa; Feltes, Timothy F
2017-05-01
The treatment of children with cardiac disease is one of the most prevalent and costly pediatric inpatient conditions. The design of inpatient medical services for children admitted to and discharged from noncritical cardiology care units, however, is undefined. North American Pediatric Cardiology Programs were surveyed to define noncritical cardiac care unit models in current practice. An online survey that explored institutional and functional domains for noncritical cardiac care unit was crafted. All questions were multi-choice with comment boxes for further explanation. The survey was distributed by email four times over a 5-month period. Most programs (n = 45, 60%) exist in free-standing children's hospitals. Most programs cohort cardiac patients on noncritical cardiac care units that are restricted to cardiac patients in 39 (54%) programs or restricted to cardiac and other subspecialty patients in 23 (32%) programs. The most common frontline providers are categorical pediatric residents (n = 58, 81%) and nurse practitioners (n = 48, 67%). However, nurse practitioners are autonomous providers in only 21 (29%) programs. Only 33% of programs use a postoperative fast-track protocol. When transitioning care to referring physicians, most programs (n = 53, 72%) use facsimile to deliver pertinent patient information. Twenty-two programs (31%) use email to transition care, and eighteen (25%) programs use verbal communication. Most programs exist in free-standing children's hospitals in which the noncritical cardiac care units are in some form restricted to cardiac patients. While nurse practitioners are used on most noncritical cardiac care units, they rarely function as autonomous providers. The majority of programs in this survey do not incorporate any postoperative fast-track protocols in their practice. Given the current era of focused handoffs within hospital systems, relatively few programs utilize verbal handoffs to the referring pediatric cardiologist/pediatrician. © 2016 Wiley Periodicals, Inc.
NASA's new university engineering space research programs
NASA Technical Reports Server (NTRS)
Sadin, Stanley R.
1988-01-01
The objective of a newly emerging element of NASA's university engineering programs is to provide a more autonomous element that will enhance and broaden the capabilities in academia, enabling them to participate more effectively in the U.S. civil space program. The programs utilize technical monitors at NASA centers to foster collaborative arrangements, exchange of personnel, and the sharing of facilities between NASA and the universities. The elements include: the university advanced space design program, which funds advanced systems study courses at the senior and graduate levels; the university space engineering research program that supports cross-disciplinary research centers; the outreach flight experiments program that offers engineering research opportunities to universities; and the planned university investigator's research program to provide grants to individuals with outstanding credentials.
Autonomous landing guidance program
NASA Astrophysics Data System (ADS)
Brown, John A.
1996-05-01
The Autonomous Landing Guidance program is partly funded by the US Government under the Technology Reinvestment Project. The program consortium consists of avionics and other equipment vendors, airlines and the USAF. A Sextant Avionique HUD is used to present flight symbology in cursive form as well as millimeter wave radar imagery from Lear Astronics equipment and FLIR Systems dual-channel, forward-looking, infrared imagery. All sensor imagery is presented in raster form. A future aim is to fuse all imagery data into a single presentation. Sensor testing has been accomplished in a Cessna 402 operated by the Maryland Advanced Development Laboratory. Development testing is under way in a Northwest Airlines simulator equipped with HUD and image simulation. Testing is also being carried out using United Airlines Boeing 727 and USAF C-135C (Boeing 707) test aircraft. The paper addresses the technology utilized in sensory and display systems as well as modifications made to accommodate the elements in the aircraft. Additions to the system test aircraft include global positioning systems, inertial navigation systems and extensive data collection equipment. Operational philosophy and benefits for both civil and military users are apparent. Approach procedures have been developed allowing use of Category 1 ground installations in Category 3 conditions.
Impact of splenic hilar lymph node metastasis on prognosis in patients with advanced gastric cancer.
Son, Taeil; Kwon, In Gyu; Lee, Joong Ho; Choi, Youn Young; Kim, Hyoung-Il; Cheong, Jae-Ho; Noh, Sung Hoon; Hyung, Woo Jin
2017-10-13
Impact of splenic hilar LN dissection during total gastrectomy for proximal advanced gastric cancer is controversial. The objective of this study was to assess the impact on prognosis of splenic hilar lymph node(LN) metastasis compared to that of metastasis to other regional LN groups. Patients who underwent total gastrectomy with D2 LN dissection from 2000 to 2010 were reviewed retrospectively. The clinicopathologic characteristics and long-term results of patients with splenic hilar LN metastasis were compared to those of patients with only metastasis to other extraperigastric LNs (stations #8a, #9, #11, or #12a). To investigate the survival benefit of performing splenic hilar LN dissection, the estimated therapeutic index for the procedure was calculated by multiplying the incidence of metastases in the hilar region by the survival rates for individuals with nodal involvement in that region. Of 602 patients, 87(14.5%) had hilar LN metastasis. The 5-year overall and relapse-free survival rates for patients with hilar LN metastasis were 24.1% and 12.1%, respectively. These rates were similar to those for patients with metastasis to other extraperigastric LNs ( P > 0.05), with similar recurrence patterns. Overall survival in the hilar LN metastasis group was better than that for patients with distant metastasis( P < 0.05). The estimated therapeutic index of splenic hilar LN dissection was 3.5, which was similar to index values for LN dissection at other extraperigastric LNs. Dissection of splenic hilar LNs during total gastrectomy for advanced gastric cancer allows for a prognosis similar to that achieved with dissection of extraperigastric LNs.
Zhou, Xiang; Chen, Ruohua; Huang, Gang; Liu, Jianjun
2017-01-01
We assessed the clinical value of 2-fluoro-2-deoxyglucose (18F-FDG) PET/CT imaging for predicting occult nodal metastasis in non-small cell lung cancer (NSCLC) patients. This retrospective study included 54 patients with T1-2N0M0 NSCLC who had undergone 18F-FDG PET/CT before surgery. Occult nodal metastasis was detected in 25.9% (14/54) of the patients. Immunohistochemical analysis revealed that increased glucose transporter 1 expression was associated with occult nodal metastasis, but hexokinase 2 expression was not. Compared to the negative nodal metastasis group, the positive nodal metastasis group was associated with increased maximum standardized uptake value (SUVmax) and tumor size. Multivariate analysis indicated that SUVmax and tumor size were associated with nodal metastasis. Nodal metastasis could be predicted with a sensitivity of 92.9% and a specificity of 55.0% when the SUVmax cutoff was 4.35. When patients were divided into low-risk (tumor size ≤ 2.5 cm and SUVmax ≤ 4.35), moderate-risk (tumor size ≤ 2.5 cm and SUVmax > 4.35 or tumor size > 2.5 cm and SUVmax ≤ 4.35) and high-risk (tumor size > 2.5 cm and SUVmax > 4.35) groups, the lymph node metastasis rates were 4.3%, 22.7%, and 88.9%, respectively. These results indicate that the combination of SUVmax and tumor size has potential clinical value for predicting occult nodal metastasis in NSCLC patients. PMID:29137276
Engin, H. Billur; Guney, Emre; Keskin, Ozlem; Oliva, Baldo; Gursoy, Attila
2013-01-01
Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis. PMID:24278371
Brain metastasis in gastroesophageal adenocarcinoma and HER2 status.
Limon, Dror; Gal, Omer; Gordon, Noa; Katz, Lior; Perl, Gali; Purim, Ofer; Amit, Limor; Stemmer, Salomon M; Kundel, Yulia; Ben-Aharon, Irit; Brenner, Baruch; Siegal, Tali; Yust-Katz, Shlomit
2018-06-01
The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011-2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1-9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.
Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study.
Wu, Wenrui; He, Xingkang; Andayani, Dewi; Yang, Liya; Ye, Jianzhong; Li, Yating; Chen, Yanfei; Li, Lanjuan
2017-01-01
Background and Aims : Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.
Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.
Ren, Yijiu; Dai, Chenyang; Zheng, Hui; Zhou, Fangyu; She, Yunlang; Jiang, Gening; Fei, Ke; Yang, Ping; Xie, Dong; Chen, Chang
2016-08-16
Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.
Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang
2014-01-01
Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.
Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang
2014-01-01
Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways. PMID:25162296
Wang, Lei; Chen, Chen; Li, Fen; Hua, Qing-Quan; Chen, Shiming; Xiao, Bokui; Dai, Mengyuan; Li, Man; Zheng, Anyuan; Yu, Di; Hu, Zhang Wei; Tao, Zezhang
2016-01-01
Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction-inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC. PMID:27279246
Park, Jae-Yong; Koo, Bon Seok
2014-06-01
Despite an excellent prognosis, cervical lymph node (LN) metastases are common in patients with papillary thyroid cancer (PTC). The presence of metastasis is associated with an increased risk of locoregional recurrence, which significantly impairs quality of life and may decrease survival. Therefore, it has been an important determinant of the extent of lateral LN dissection in the initial treatment of PTC patients with lateral cervical metastasis. However, the optimal extent of therapeutic lateral neck dissection (ND) remains controversial. Optimizing the surgical extent of LN dissection is fundamental for balancing the surgical morbidity and oncological benefits of ND in PTC patients with lateral neck metastasis. We reviewed the currently available literature regarding the optimal extent of lateral LN dissection in PTC patients with lateral neck metastasis. Even in cases with suspicion of metastatic LN at the single lateral level or isolated metastatic lateral LN, the application of ND including all sublevels from IIa and IIb to Va and Vb may be overtreatment, due to the surgical morbidity. When there is no suspicion of LN metastasis at levels II and V, or when multilevel aggressive neck metastasis is not found, sublevel IIb and Va dissection may not be necessary in PTC patients with lateral neck metastasis. Thus consideration of the individualized optimal surgical extent of lateral ND is important when treating PTC patients with lateral cervical metastasis.
Huang, Gao-Xiang; Wang, Yan; Su, Jie; Zhou, Peng; Li, Bo; Yin, Li-Juan; Lu, Jian
2017-12-01
Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis. Copyright © 2017. Published by Elsevier B.V.
Clinicopathological features of gastric metastasis from breast cancer in three cases.
Koike, Kenta; Kitahara, Kenji; Higaki, Mayumi; Urata, Masako; Yamazaki, Fumio; Noshiro, Hirokazu
2014-09-01
The common sites for metastases from breast cancer are lymph nodes, bone, lung, liver, and brain. Gastrointestinal (GI) metastasis is rarely found or diagnosed in patients with breast cancer. This report presents three cases of gastric metastasis from breast cancer. Case 1 was a 42-year-old female diagnosed with gastric metastasis after mastectomy with axillary lymph node dissection for invasive lobular carcinoma of the left breast. Case 2 was a 54-year-old female who was diagnosed to have invasive lobular carcinoma of the left breast with systemic bone and gastric metastasis. Case 3 was a 54-year-old female who was diagnosed to have bilateral invasive ductal carcinoma of the breast with simultaneous bone and gastric metastasis. The immunohistochemical statuses for estrogen receptor, progesterone receptor, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15) between the primary and gastric metastatic lesions were all well matched. All three cases were treated with systemic chemotherapy, hormone therapy or both, without surgical intervention for gastric lesions. Two patients with disseminated disease died 27 and 58 months after diagnosis of gastric metastasis, while one patient without organ metastasis is still alive at 56 months after diagnosis. It is important to make a correct diagnosis by distinguishing gastric metastasis from breast cancer in order to select the optimal initial treatment for systemic disease of breast cancer.
Regulation and Function of Cytokines that Predict Prostate Cancer Metastasis
2011-08-01
Ph.D. Cedar-Sinai Medical Center Los Angeles, CA 90048 W81XWH-09-1-0503 11 bhowmickn@cshs.org Table of Contents Introduction...Professor, Medicine Uro -Oncology Research Program Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center 8750 Beverly Blvd...Atrium 103 Los Angeles, CA 90048 Tel: (310) 423-5992 Fax: (310) 423-8543 Email: bhowmickn@cshs.org Please note the grant has been transferred
Fassnacht, Martin; Arlt, Wiebke; Bancos, Irina; Dralle, Henning; Newell-Price, John; Sahdev, Anju; Tabarin, Antoine; Terzolo, Massimo; Tsagarakis, Stylianos; Dekkers, Olaf M
2016-08-01
: By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas. © 2016 European Society of Endocrinology.
Perception system and functions for autonomous navigation in a natural environment
NASA Technical Reports Server (NTRS)
Chatila, Raja; Devy, Michel; Lacroix, Simon; Herrb, Matthieu
1994-01-01
This paper presents the approach, algorithms, and processes we developed for the perception system of a cross-country autonomous robot. After a presentation of the tele-programming context we favor for intervention robots, we introduce an adaptive navigation approach, well suited for the characteristics of complex natural environments. This approach lead us to develop a heterogeneous perception system that manages several different terrain representatives. The perception functionalities required during navigation are listed, along with the corresponding representations we consider. The main perception processes we developed are presented. They are integrated within an on-board control architecture we developed. First results of an ambitious experiment currently underway at LAAS are then presented.
Robust control of multi-jointed arm with a decentralized autonomous control mechanism
NASA Technical Reports Server (NTRS)
Kimura, Shinichi; Miyazaki, Ken; Suzuki, Yoshiaki
1994-01-01
A decentralized autonomous control mechanism applied to the control of three dimensional manipulators and its robustness to partial damage was assessed by computer simulation. Decentralized control structures are believed to be quite robust to time delay between the operator and the target system. A 10-jointed manipulator based on our control mechanism was able to continue its positioning task in three-dimensional space without revision of the control program, even after some of its joints were damaged. These results suggest that this control mechanism can be effectively applied to space telerobots, which are associated with serious time delay between the operator and the target system, and which cannot be easily repaired after being partially damaged.
Autonomous rendezvous and capture development infrastructure
NASA Technical Reports Server (NTRS)
Bryan, Thomas C.; Roe, Fred; Coker, Cindy; Nelson, Pam; Johnson, B.
1991-01-01
In the development of the technology for autonomous rendezvous and docking, key infrastructure capabilities must be used for effective and economical development. This involves facility capabilities, both equipment and personnel, to devise, develop, qualify, and integrate ARD elements and subsystems into flight programs. One effective way of reducing technical risks in developing ARD technology is the use of the ultimate test facility, using a Shuttle-based reusable free-flying testbed to perform a Technology Demonstration Test Flight which can be structured to include a variety of additional sensors, control schemes, and operational approaches. This conceptual testbed and flight demonstration will be used to illustrate how technologies and facilities at MSFC can be used to develop and prove an ARD system.
Proceedings of the 8th Annual Summer Conference: NASA/USRA Advanced Design Program
NASA Technical Reports Server (NTRS)
1992-01-01
Papers presented at the 8th Annual Summer Conference are categorized as Space Projects and Aeronautics projects. Topics covered include: Systematic Propulsion Optimization Tools (SPOT), Assured Crew Return Vehicle Post Landing Configuration Design and Test, Autonomous Support for Microorganism Research in Space, Bioregenerative System Components for Microgravity, The Extended Mission Rover (EMR), Planetary Surface Exploration MESUR/Autonomous Lunar Rover, Automation of Closed Environments in Space for Human Comfort and Safety, Walking Robot Design, Extraterrestrial Surface Propulsion Systems, The Design of Four Hypersonic Reconnaissance Aircraft, Design of a Refueling Tanker Delivering Liquid Hydrogen, The Design of a Long-Range Megatransport Aircraft, and Solar Powered Multipurpose Remotely Powered Aircraft.
Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with
Competition and niche construction in a model of cancer metastasis.
Qian, Jimmy J; Akçay, Erol
2018-01-01
Niche construction theory states that not only does the environment act on populations to generate Darwinian selection, but organisms reciprocally modify the environment and the sources of natural selection. Cancer cells participate in niche construction as they alter their microenvironments and create pre-metastatic niches; in fact, metastasis is a product of niche construction. Here, we present a mathematical model of niche construction and metastasis. Our model contains producers, which pay a cost to contribute to niche construction that benefits all tumor cells, and cheaters, which reap the benefits without paying the cost. We derive expressions for the conditions necessary for metastasis, showing that the establishment of a mutant lineage that promotes metastasis depends on niche construction specificity and strength of interclonal competition. We identify a tension between the arrival and invasion of metastasis-promoting mutants, where tumors composed only of cheaters remain small but are susceptible to invasion whereas larger tumors containing producers may be unable to facilitate metastasis depending on the level of niche construction specificity. Our results indicate that even if metastatic subclones arise through mutation, metastasis may be hindered by interclonal competition, providing a potential explanation for recent surprising findings that most metastases are derived from early mutants in primary tumors.
Shi, Jun; Wei, Pin-Kang; Zhang, Shen; Qin, Zhi-Feng; Li, Jun; Sun, Da-Zhi; Xiao, Yan; Yu, Zhi-Hong; Lin, Hui-Ming; Zheng, Guo-Jing; Su, Xiao-Mei; Chen, Ya-Lin; Liu, Yan-Fang; Xu, Ling
2008-01-01
AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthotopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplan-tation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors. PMID:18720543
NASA Astrophysics Data System (ADS)
Gross, John E.; Minato, Rick; Smith, David M.; Loftin, R. B.; Savely, Robert T.
1991-10-01
AI techniques are shown to have been useful in such aerospace industry tasks as vehicle configuration layouts, process planning, tool design, numerically-controlled programming of tools, production scheduling, and equipment testing and diagnosis. Accounts are given of illustrative experiences at the production facilities of three major aerospace defense contractors. Also discussed is NASA's autonomous Intelligent Computer-Aided Training System, for such ambitious manned programs as Space Station Freedom, which employs five different modules to constitute its job-independent training architecture.
Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.
Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri
2007-08-15
L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.
In vitro three-dimensional cancer metastasis modeling: Past, present, and future
NASA Astrophysics Data System (ADS)
Wei-jing, Han; Wei, Yuan; Jiang-rui, Zhu; Qihui, Fan; Junle, Qu; Li-yu, Liu
2016-01-01
Metastasis is the leading cause of most cancer deaths, as opposed to dysregulated cell growth of the primary tumor. Molecular mechanisms of metastasis have been studied for decades and the findings have evolved our understanding of the progression of malignancy. However, most of the molecular mechanisms fail to address the causes of cancer and its evolutionary origin, demonstrating an inability to find a solution for complete cure of cancer. After being a neglected area of tumor biology for quite some time, recently several studies have focused on the impact of the tumor microenvironment on cancer growth. The importance of the tumor microenvironment is gradually gaining attention, particularly from the perspective of biophysics. In vitro three-dimensional (3-D) metastatic models are an indispensable platform for investigating the tumor microenvironment, as they mimic the in vivo tumor tissue. In 3-D metastatic in vitro models, static factors such as the mechanical properties, biochemical factors, as well as dynamic factors such as cell-cell, cell-ECM interactions, and fluid shear stress can be studied quantitatively. With increasing focus on basic cancer research and drug development, the in vitro 3-D models offer unique advantages in fundamental and clinical biomedical studies. Project supported by the National Basic Research Program of China (Grant No. 2013CB837200), the National Natural Science Foundation of China (Grant No. 11474345), and the Beijing Natural Science Foundation, China (Grant No. 7154221).
Xu, Shuhang; Feng, Lingling; Chen, Yongming; Sun, Ying; Lu, Yao; Huang, Shaomin; Fu, Yang; Zheng, Rongqin; Zhang, Yujing; Zhang, Rong
2017-06-20
In order to refine the location and metastasis-risk density of 16 lymph node stations of gastric cancer for neoadjuvant radiotherapy, we retrospectively reviewed the initial images and pathological reports of 255 gastric cancer patients with lymphatic metastasis. Metastatic lymph nodes identified in the initial computed tomography images were investigated by two radiologists with gastrointestinal specialty. A circle with a diameter of 5 mm was used to identify the central position of each metastatic lymph node, defined as the LNc (the central position of the lymph node). The LNc was drawn at the equivalent location on the reference images of a standard patient based on the relative distances to the same reference vessels and the gastric wall using a Monaco® version 5.0 workstation. The image manipulation software Medi-capture was programmed for image analysis to produce a contour and density atlas of 16 lymph node stations. Based on a total of 2846 LNcs contoured (31-599 per lymph node station), we created a density distribution map of 16 lymph node drainage stations of the stomach on computed tomography images, showing the detailed radiographic delineation of each lymph node station as well as high-risk areas for lymph node metastasis. Our mapping can serve as a template for the delineation of gastric lymph node stations when defining clinical target volume in pre-operative radiotherapy for gastric cancer.
[Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].
Meng, X Y; Song, S T
2017-03-23
Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.
Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis
Chen, Xi; Cao, Xinwei; Sun, Xiaohua; Lei, Rong; Chen, Pengfei; Zhao, Yongxu; Jiang, Yuhang; Yin, Jie; Chen, Ran; Ye, Deji; Wang, Qi; Liu, Zhanjie; Liu, Sanhong; Cheng, Chunyan; Mao, Jie; Hou, Yingyong; Wang, Mingliang; Siebenlist, Ulrich; Eugene Chin, Y; Wang, Ying; Cao, Liu; Hu, Guohong; Zhang, Xiaoren
2016-01-01
Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFβ signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFβ treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis. PMID:27906182
Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.
2015-01-01
Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801
Ethanol inhibits B16-BL6 melanoma metastasis and cell phenotypes associated with metastasis.
Kushiro, Kyoko; Núñez, Nomelí P
2012-01-01
Every year, approximately 68,000 new cases of malignant melanoma are diagnosed in the US. Ethanol consumption inhibits metastasis of melanoma in mice, but the mechanism is not well understood. C57BL/6J ob/+ mice, given either water or 20% ethanol, were injected intravenously with B16-BL6 melanoma cells to determine pulmonary metastasis. The effects of ethanol on cell phenotypes and markers of the epithelial-to-mesenchymal transition were determined in cell culture. In mice, ethanol consumption inhibited experimental pulmonary metastasis. This inhibition was associated with decreased body weight, and levels of systemic leptin, and insulin. In cell culture, ethanol inhibited B16-BL6 cell motility, invasion, and anchorage-independent growth. Additionally, ethanol reduced Snai1 expression and increased E-cadherin expression. Lastly, ethanol increased the expression of Kiss1 metastasis-suppressor and the metastasis suppressor Nm23/nucleoside diphosphate kinase. In both animal and in cell culture conditions, ethanol inhibited the metastatic ability of B16-BL6 melanoma cells.
Transient SNAIL1 expression is necessary for metastatic competence in breast cancer.
Tran, Hung D; Luitel, Krishna; Kim, Michael; Zhang, Kun; Longmore, Gregory D; Tran, David D
2014-11-01
SNAIL1 has been suggested to regulate breast cancer metastasis based on analyses of human breast tumor transcriptomes and experiments using cancer cell lines and xenografts. However, in vivo genetic experimental support for a role for SNAIL1 in breast cancer metastasis that develops in an immunocompetent tumor microenvironment has not been determined. To address this question, we created a genetic SNAIL1 model by coupling an endogenous SNAIL1 reporter with an inducible SNAIL1 transgene. Using multiple genetic models of breast cancer, we demonstrated that endogenous SNAIL1 expression was restricted to primary tumors that ultimately disseminate. SNAIL1 gene deletion either during the premalignant phase or after primary tumors have reached a palpable size blunted metastasis, indicating that late metastasis was the main driver of metastasis and that this was dependent on SNAIL1. Importantly, SNAIL1 expression during breast cancer metastasis was transient and forced transient, but not continuous. SNAIL1 expression in breast tumors was sufficient to increase metastasis. ©2014 American Association for Cancer Research.
[Encounter of cancer cells with bone. Histological examination of bone metastasis].
Kanda, Hiroaki
2011-03-01
Management of the cancer bone metastasis is important clinical problem. The mechanism (s) of bone metastasis has been studied mainly by animal models and in vitro system. There might be discrepancy between model systems and in vivo human clinical materials. But there is surprisingly rare study of histological examination of human skeletal metastasis, since it is hard to obtain human materials without modification by chemotherapy or irradiation. There are many surgical materials suitable for this examination in our hospital and we have been examined histological features of them. Stromal cells between metastatic cancer cells and OCs (osteoclasts) and÷or OBs (osteoblasts) might play a role in bone metastasis, since these cells are frequently accompanied with OCs÷OBs. We called these stromal cells as "fibroblast-like cells" and examined their nature and roles in bone metastasis. We hope these fibroblast-like cells might become the target of anti bone metastasis therapy, same as osteoclasts targeted by bisphosphonates.
Avgerinou, Georgia; Flessas, Ioannis; Hatziolou, Eftychia; Zografos, Georgios; Nitsios, Ilias; Zagouri, Flora; Katsambas, Andreas; Kanitakis, Jean
2011-06-01
Cutaneous metastasis of gastric adenocarcinoma is rare and usually presents in men, as nodules over the abdomen. We present the case of a woman with cutaneous metastasis of gastric adenocarcinoma showing unusual clinicopathological features. A 37-year-old woman developed florid cutaneous metastasis over the skin of the left breast two years after total gastrectomy for a signet-ring adenocarcinoma of the diffuse type. The metastasis presented as a multinodular growth developing over erythematous skin of the left hemithorax. Microscopically, the skin tumor was predominantly made up of spindle-shaped cells, mimicking a mesenchymal/fibrohistiocytic neoplasm. A comparative immunohistochemical study of the gastric primary and the skin tumor showed an almost identical profile (keratin 7/20+; epithelial membrane antigen+, MUC-5AC+), highlighting the gastric adenocarcinoma as the origin of the skin metastasis. Although rare, cutaneous metastases of gastric adenocarcinomas can develop in women and may mimic inflammatory metastasis of breast adenocarcinoma. Immunohistochemistry is invaluable in establishing the correct diagnosis.
Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok
2014-09-01
Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.
The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis
Goddard, Erica T.; Hill, Ryan C.; Nemkov, Travis; D’Alessandro, Angelo; Hansen, Kirk C.; Maller, Ori; Mongoue-Tchokote, Solange; Mori, Motomi; Partridge, Ann H.; Borges, Virginia F.; Schedin, Pepper
2017-01-01
Postpartum breast cancer patients are at increased risk for metastasis compared to age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the post-lactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, ECM remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a pro-metastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning Balb/c mice compared to nulliparous controls. Human relevance is suggested by a ~3-fold increase in liver metastasis in postpartum breast cancer patients (n=564) and by liver-specific tropism (n=117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer. PMID:27974414
MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor
Wu, Kaichun; Liu, Jie; Sun, Shiren; Guo, Xuegang; Wang, Biaoluo; Gang, Yi; Zhang, Yongguo; Li, Quanjiang; Qiao, Taidong; Zhao, Qingchuan; Nie, Yongzhan; Fan, Daiming
2010-01-01
MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis. PMID:20300657
NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice
Puchalapalli, Madhavi; Zeng, Xianke; Mu, Liang; Anderson, Aubree; Hix Glickman, Laura; Zhang, Ming; Sayyad, Megan R.; Mosticone Wangensteen, Sierra; Clevenger, Charles V.; Koblinski, Jennifer E.
2016-01-01
Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model. PMID:27662655
Funazo, Tomoko; Morita, Kyohei; Ikegami, Naoya; Konishi, Chisato; Nakao, Satoshi; Ariyasu, Ryo; Taki, Masato; Nakagawa, Kazuhiko; Hwang, Moon Hee; Yoshimura, Chie; Wakayama, Toshiaki; Nishizaka, Yasuo
2017-01-01
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy. Alectinib may be the best treatment for choroidal metastasis in patients harboring an ALK translocation because of its favorable side effect profile involving visual disturbances. PMID:28794371
Wang, Mozhi; Wang, Mengshen; Wang, Zhenning; Yu, Xueting; Song, Yongxi; Wang, Chong; Xu, Yujie; Wei, Fengheng; Zhao, Yi; Xu, Yingying
2018-06-01
Breast cancer (BC) is an aggressive malignant disease in women worldwide with a high tendency to metastasize. However, important biomarkers for BC metastasis remain largely undefined. In the present study, we identified that long non-coding RNA-CTD-2108O9.1 is downregulated in BC tissues and cells and acts as a metastatic inhibitor of BC. Mechanistic investigation determined that lncRNA-CTD-2108O9.1 represses metastasis by targeting leukemia inhibitory factor receptor (LIFR), which is designated as a metastasis suppressor in BC. Our study characterizes a significant tumor suppressor active in BC metastasis repression through the known metastasis inhibitor LIFR. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Sudden loss of vision due to breast cancer metastasis to the eyeball.
Antosz, Zbigniew S; Walocha, Jerzy; Poręba, Ryszard; Sioma-Markowska, Urszula
2014-01-01
Intraocular choroidal metastasis is a very rare cause of blindness. Carcinoma of breast is the most common primary malignancy the accounts for choroidal metastasis in females. Other primary neoplasms which can uncommonly metastasize to the choroid are gastrointestinal tract, thyroid, pancreas, prostate and testis. Metastatic neoplasm to the eye outnumbers the primary tumors such as retinoblastoma and malignant melanoma. We present a case of sudden loss of vision due to breast cancer metastasis to the eyeball. The interval between the diagnosis of the primary tumor and the choroidal metastasis was 4 years.
Solitary fibular metastasis from nonsmall cell lung carcinoma
Akram, Mohammad; Zaheer, Samreen; Hussain, Asif; Siddiqui, Shahid A; Afrose, Ruquiya; Khalid, Saifullah
2017-01-01
Solitary bone metastasis to fibula in patients of lung carcinoma is a rare entity, with only four cases reported in literature. We, hereby, present a case of a 50 year-old-male who was given three cycles of chemotherapy for lung carcinoma with no distant metastasis but presented 2 months later with a fusiform, painful swelling around the knee that was clinically suspected to be inflammatory in nature but proved to be fibular metastasis on cytology. There was no evidence of skeletal metastasis on initial bone scan. He was given palliative radiotherapy for this with symptomatic relief. PMID:28469322
Solitary fibular metastasis from nonsmall cell lung carcinoma.
Akram, Mohammad; Zaheer, Samreen; Hussain, Asif; Siddiqui, Shahid A; Afrose, Ruquiya; Khalid, Saifullah
2017-01-01
Solitary bone metastasis to fibula in patients of lung carcinoma is a rare entity, with only four cases reported in literature. We, hereby, present a case of a 50 year-old-male who was given three cycles of chemotherapy for lung carcinoma with no distant metastasis but presented 2 months later with a fusiform, painful swelling around the knee that was clinically suspected to be inflammatory in nature but proved to be fibular metastasis on cytology. There was no evidence of skeletal metastasis on initial bone scan. He was given palliative radiotherapy for this with symptomatic relief.
Autonomic nervous system correlates in movement observation and motor imagery
Collet, C.; Di Rienzo, F.; El Hoyek, N.; Guillot, A.
2013-01-01
The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes. PMID:23908623
Review of Airport Ground Traffic Models Including an Evaluation of the ASTS Computer Program
DOT National Transportation Integrated Search
1972-12-01
The report covers an evaluation of Airport Ground Traffic models for the purpose of simulating an Autonomous Local Intersection Controller. All known models were reviewed and a detailed study was performed on the two in-house models the ASTS and ROSS...
United Kingdom: Quality with Control.
ERIC Educational Resources Information Center
Paulu, Burton
1978-01-01
Describes the autonomous workings of the British Broadcasting Corporation and the Independent Broadcasting Authority, where editorializing is prohibited, advertising is limited, and the aim of programing is to provide the public with real choices at all hours, and to maintain high standards of planning, writing, production, and presentation. (JMF)
Li, Mingli; Li, Rongjian; Shen, Zhiyong; Li, Chunying; Liang, Nengxiu; Peng, Zhenren; Huang, Wenbo; He, Chongwei; Zhong, Feng; Tang, Xianyan; Lan, Guanghua
2017-09-30
A methadone maintenance treatment (MMT) program to curb the dual epidemics of HIV/AIDS and drug use has been administered by China since 2004. Little is known regarding the geographic heterogeneity of HIV and hepatitis C virus (HCV) infections among MMT clients in the resource-constrained context of Chinese provinces, such as Guangxi. This study aimed to characterize the geographic distribution patterns and co-clustered epidemic factors of HIV, HCV and co-infections at the county level among drug users receiving MMT in Guangxi Zhuang Autonomous Region, located in the southwestern border area of China. Baseline data on drug users' demographic, behavioral and biological characteristics in the MMT clinics of Guangxi Zhuang Autonomous Region during the period of March 2004 to December 2014 were obtained from national HIV databases. Residential addresses were entered into a geographical information system (GIS) program and analyzed for spatial clustering of HIV, HCV and co-infections among MMT clients at the county level using geographic autocorrelation analysis and geographic scan statistics. A total of 31,015 MMT clients were analyzed, and the prevalence of HIV, HCV and co-infections were 13.05%, 72.51% and 11.96% respectively. Both the geographic autocorrelation analysis and geographic scan statistics showed that HIV, HCV and co-infections in Guangxi Zhuang Autonomous Region exhibited significant geographic clustering at the county level, and the Moran's I values were 0.33, 0.41 and 0.30, respectively (P < 0.05). The most significant high-risk overlapping clusters for these infections were restricted to within a 10.95 km 2 radius of each of the 13 locations where P county was the cluster center. These infections also co-clustered with certain characteristics, such as being unmarried, having a primary level of education or below, having used drugs for more than 10 years, and receptive sharing of syringes with others. The high-risk clusters for these characteristics were more likely to reside in the areas surrounding P county. HIV, HCV and co-infections among MMT clients in Guangxi Zhuang Autonomous Region all presented substantial geographic heterogeneity at the county level with a number of overlapping significant clusters. The areas surrounding P county were effective in enrolling high-risk clients in their MMT programs which, in turn, might enable people who inject drugs to inject less, share fewer syringes, and receive referrals for HIV or HCV treatment in a timely manner.
Dissecting and Targeting Latent Metastasis
2014-09-01
metastasis of breast cancer (LMBC). These cells retain the potential to form overt metastasis for years. Targeting LMBC with new drugs offers an...cancer cell extravasation through the BBB in experimental models and predict brain metastasis in the clinic (16). Once inside the brain parenchyma... drugs that perturb gap junction activity (Chen et al submitted for publication). In our experiments, both drugs as single agents were effective
Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis
2014-09-01
13. SUPPLEMENTARY NOTES 14. ABSTRACT Bone is the most common site of metastasis for human breast cancer (BCa), which results in significant...to all major bones as in human patients. 15. SUBJECT TERMS Bone metastasis; osteolysis; osteoprotegerin 16. SECURITY CLASSIFICATION OF: 17...metastasis for human breast cancer (BCa), which results in significant morbidity and mortality in patients with advanced disease. A vicious cycle
Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with other proteins.
Liu, Yanhong; Zhou, Renke; Baumbusch, Lars O.; Tsavachidis, Spyros; Brewster, Abenaa M.; Do, Kim-Anh; Sahin, Aysegul; Hortobagyi, Gabriel N.; Taube, Joseph H.; Mani, Sendurai A.; Aarøe, Jørgen; Wärnberg, Fredrik; Børresen-Dale, Anne-Lise; Mills, Gordon B.; Thompson, Patricia A.; Bondy, Melissa L.
2014-01-01
Purpose To identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Patients and Methods Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Results Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3–22.2, 3q27.1, 10q23.1, and 14q13.2–3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios (HRs). For bone metastasis, the hazard (95% confidence interval) for the low-risk group was 0.32 (0.11–0.92) compared to the intermediate-risk group and 2.99 (1.74–5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17–0.66) and 2.33 (1.59–3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Conclusions Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk. PMID:24305980
Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S
2018-03-23
Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk of central cervical lymph node metastasis, and we shall suggest prophylactic central lymph cervical node dissection.
Kimura, Hiroaki; Fujibayashi, Shunsuke; Shimizu, Takayoshi; Otsuki, Bungo; Murakami, Hideki; Kaido, Toshimi; Uemoto, Shinji; Matsuda, Shuichi
2015-08-15
Case report. We report a patient who was successfully treated with total en bloc spondylectomy (TES) for T7 metastasis after living donor liver transplantation for hepatocellular carcinoma (HCC). Spinal metastasis from HCC has a poor prognosis. There are only a few studies on surgical outcomes of spinal metastasis from HCC. Because of the high surgical morbidity and short life expectancy in patients with HCC with spinal metastasis, TES is not considered in these patients, although several studies have reported satisfactory results for TES for some types of metastatic spinal tumors. Liver transplantation (LT) is the curative treatment option for early HCC. However, the recurrence of HCC is a possible problem after LT, although no reports on surgery for spinal metastasis following LT for HCC have been published. We report on the first case of a patient who was successfully treated with TES for T7 metastasis after living donor LT for HCC. The patient was a 65-year-old man, who had undergone living donor LT for HCC 2 years before. His main symptom was progressive gait disturbance because of the spinal cord compression by the tumor at T7. Radiology and pathology examinations revealed a solitary metastasis at T7 with neither recurrence in the liver nor metastasis in the other organs. We performed TES using a pedicle screw system and a mesh cage filled with frozen autografts. After surgery, the patient showed clear improvement in neurological symptoms. At 3 months after surgery, a T4 metastasis was detected with magnetic resonance imaging, and the patient was treated with heavy ion radiotherapy. He could walk without a cane and there was no evidence of recurrence at 1.5 years after surgery. Solitary spinal metastasis of HCC may become an indication for TES if liver function improves after LT. 5.
Identifying the potential long-term survivors among breast cancer patients with distant metastasis.
Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G
2016-05-01
We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Cigarette Smoking and Risk of Lung Metastasis from Esophageal Cancer
Abrams, Julian A.; Lee, Paul C.; Port, Jeffrey L.; Altorki, Nasser K.; Neugut, Alfred I.
2008-01-01
Background While extensive research has explored the impact of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer. Methods We performed a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association. Results We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39/53) were ever smokers, versus 47.8% (144/301) of patients without lung metastases (p=0.001) (summary OR 2.52, 95%CI 1.17-5.45; stratified by histology). Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR 1.89, 95%CI 0.80-4.46). Upper esophageal subsite (OR 4.71, 95%CI 1.20-18.5) but not histology (squamous OR 0.65,95%CI 0.27-1.60) was associated with lung metastasis. Compared to the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR 2.35, 95%CI 1.11-4.97). There was no association between liver metastasis and smoking (OR 0.88, 95%CI 0.42-1.83) Conclusions Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship appears to be site-specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome. PMID:18843013
Cigarette smoking and risk of lung metastasis from esophageal cancer.
Abrams, Julian A; Lee, Paul C; Port, Jeffrey L; Altorki, Nasser K; Neugut, Alfred I
2008-10-01
Whereas extensive research has explored the effect of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer. We conducted a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association. We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39 of 53) were ever smokers, versus 47.8% (144 of 301) of patients without lung metastases [P=0.001; summary odds ratio (OR), 2.52; 95% confidence interval (95% CI), 1.17-5.45; stratified by histology]. Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR, 1.89; 95% CI, 0.80-4.46). Upper esophageal subsite (OR, 4.71; 95% CI, 1.20-18.5), but not histology (squamous OR 0.65,95% CI 0.27-1.60), was associated with lung metastasis. Compared with the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR, 2.35; 95% CI, 1.11-4.97). There was no association between liver metastasis and smoking (OR, 0.88; 95% CI, 0.42-1.83). Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship seems to be site specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome.
Impact of splenic hilar lymph node metastasis on prognosis in patients with advanced gastric cancer
Son, Taeil; Kwon, In Gyu; Lee, Joong Ho; Choi, Youn Young; Kim, Hyoung-Il; Cheong, Jae-Ho; Noh, Sung Hoon; Hyung, Woo Jin
2017-01-01
Background: Impact of splenic hilar LN dissection during total gastrectomy for proximal advanced gastric cancer is controversial. The objective of this study was to assess the impact on prognosis of splenic hilar lymph node(LN) metastasis compared to that of metastasis to other regional LN groups. Study Design Patients who underwent total gastrectomy with D2 LN dissection from 2000 to 2010 were reviewed retrospectively. The clinicopathologic characteristics and long-term results of patients with splenic hilar LN metastasis were compared to those of patients with only metastasis to other extraperigastric LNs (stations #8a, #9, #11, or #12a). To investigate the survival benefit of performing splenic hilar LN dissection, the estimated therapeutic index for the procedure was calculated by multiplying the incidence of metastases in the hilar region by the survival rates for individuals with nodal involvement in that region. Results Of 602 patients, 87(14.5%) had hilar LN metastasis. The 5-year overall and relapse-free survival rates for patients with hilar LN metastasis were 24.1% and 12.1%, respectively. These rates were similar to those for patients with metastasis to other extraperigastric LNs (P > 0.05), with similar recurrence patterns. Overall survival in the hilar LN metastasis group was better than that for patients with distant metastasis(P < 0.05). The estimated therapeutic index of splenic hilar LN dissection was 3.5, which was similar to index values for LN dissection at other extraperigastric LNs. Conclusions Dissection of splenic hilar LNs during total gastrectomy for advanced gastric cancer allows for a prognosis similar to that achieved with dissection of extraperigastric LNs. PMID:29137444
Cui, Shiyun; Zhang, Kai; Li, Chen; Chen, Jing; Pan, Yan; Feng, Bing; Lu, Lei; Zhu, Ziman; Wang, Rui; Chen, Longbang
2016-11-22
Metastasis and recurrence has become one major obstacle for further improving the survival of hepatocelluar cancer (HCC) patients. Therefore, it is critical to elucidate the mechanisms involved in HCC metastasis. This study aimed to investigate the roles of microRNA (miR)-129-3p in HCC metastasis and its possible molecular mechanisms. By using microarray analysis to compare levels of different miRNAs in HCC tissues with or without lymph node metastasis (LNM), we showed that HCC tissues with LNM had reduced levels of miR-129-3p, which was related to its promoter hypermethylation and correlated with tumor metastasis, recurrence and poor prognosis. Gain - and loss - of - function assays indicated that re-expression of miR-129-3p could reverse epithelial-mesenchymal transition (EMT), and reduce in vitro invasion and in vivo metastasis of HCC cells. Aurora-A, a serine/threonine protein kinase, was identified as a direct target of miR-129-3p. Knockdown of Aurora-A phenocopied the effect of miR-129-3p overexpression on HCC metastasis. In addition, Aurora-A upregulation could partially rescue the effect of miR-129-3p. We further demonstrated that activation of PI3K/Akt and p38-MAPK signalings were involved in miR-129-3p-mediated HCC metastasis. These findings suggest that methylation-mediated miR-129-3p downregulation promotes EMT, in vitro invasion and in vivo metastasis of HCC cells via activation of PI3K/Akt and p38-MAPK signalings partially by targeting Aurora-A. Therefore, miR-129-3p may be a novel prognostic biomarker and potential therapeutic target for HCC.
Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating Leukotriene B4.
Nosaka, Takuto; Baba, Tomohisa; Tanabe, Yamato; Sasaki, Soichiro; Nishimura, Tatsunori; Imamura, Yoshiaki; Yurino, Hideaki; Hashimoto, Shinichi; Arita, Makoto; Nakamoto, Yasunari; Mukaida, Naofumi
2018-03-01
Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis, but the roles of AMs in lung metastasis still remain elusive. An i.v. injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those of a larger size. A major 5-LOX metabolite, LTB 4 , augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB 4 than IMs. Consistently, 5-LOX-expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB 4 content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent arachidonic acid-derived tumor growth promoting mediator, LTB 4 . Copyright © 2018 by The American Association of Immunologists, Inc.
Faraji, Farhoud; Hu, Ying; Wu, Gang; Goldberger, Natalie E.; Walker, Renard C.; Zhang, Jinghui; Hunter, Kent W.
2014-01-01
Metastasis is the result of stochastic genomic and epigenetic events leading to gene expression profiles that drive tumor dissemination. Here we exploit the principle that metastatic propensity is modified by the genetic background to generate prognostic gene expression signatures that illuminate regulators of metastasis. We also identify multiple microRNAs whose germline variation is causally linked to tumor progression and metastasis. We employ network analysis of global gene expression profiles in tumors derived from a panel of recombinant inbred mice to identify a network of co-expressed genes centered on Cnot2 that predicts metastasis-free survival. Modulating Cnot2 expression changes tumor cell metastatic potential in vivo, supporting a functional role for Cnot2 in metastasis. Small RNA sequencing of the same tumor set revealed a negative correlation between expression of the Mir216/217 cluster and tumor progression. Expression quantitative trait locus analysis (eQTL) identified cis-eQTLs at the Mir216/217 locus, indicating that differences in expression may be inherited. Ectopic expression of Mir216/217 in tumor cells suppressed metastasis in vivo. Finally, small RNA sequencing and mRNA expression profiling data were integrated to reveal that miR-3470a/b target a high proportion of network transcripts. In vivo analysis of Mir3470a/b demonstrated that both promote metastasis. Moreover, Mir3470b is a likely regulator of the Cnot2 network as its overexpression down-regulated expression of network hub genes and enhanced metastasis in vivo, phenocopying Cnot2 knockdown. The resulting data from this strategy identify Cnot2 as a novel regulator of metastasis and demonstrate the power of our systems-level approach in identifying modifiers of metastasis. PMID:24322557
Site of metastasis and breast cancer mortality: a Danish nationwide registry-based cohort study.
Ording, Anne Gulbech; Heide-Jørgensen, Uffe; Christiansen, Christian Fynbo; Nørgaard, Mette; Acquavella, John; Sørensen, Henrik Toft
2017-01-01
Survival among patients with metastatic breast cancer may vary according to the site of metastasis and receptor status. We used Danish nationwide medical registries to establish a cohort of patients with metastatic breast cancer (870 with de novo metastatic disease and 3518 with recurrent disease with distant metastasis) diagnosed during 1997-2011. We examined 1-year and >1 to 5-year mortality associated with first site of metastasis and receptor expression status of the primary tumor. Cox proportional regression was used to compute confounder-adjusted mortality rate ratios (MRRs) associated with site of metastasis, stratified by receptor status. Overall 1-year and >1 to 5-year mortality risks were 36 and 69 %, respectively. Risk of death within 1 year was highest for brain-only (62 %) and liver-only (43 %) involvement and nearly the same for patients with lung-only (32 %), bone-only (32 %) involvement, and other/combination of sites (34 %). Using bone-only metastasis as reference, women with brain-only metastasis had more than two-fold increased risk of dying. The adjusted MRR for women with liver-only metastasis also was increased, though less pronounced. Patients with lung-only [adjusted MRR 0.9 (95 % confidence interval (CI) 0.8, 1.1)] or other metastases [adjusted MRR 1.0 (95 % CI 0.9, 1.2)] had similar mortality as patients with bone-only metastasis. Positive hormonal receptor status was a favorable prognostic factor. Metastatic breast cancer has a serious prognosis. Patients with brain-only metastasis had the highest mortality. Positive hormonal receptor status on the primary tumor was a favorable prognostic factor for all metastatic sites.
Connolly, C; Madden, S F; Buggy, D J; Gallagher, H C
2017-01-01
Retrospective analyses suggest anaesthetic-analgesics technique during cancer surgery may affect recurrence/metastasis. This could involve direct effects of anaesthetic-analgesic drugs on cancer cells. While μ-opioid receptor over-expression in lung tumours is associated with greater metastasis, other anaesthetic-analgesic receptor targets in cancer recurrence/metastasis remain unexplored. Therefore, we evaluated the association between genetic expression of anaesthetic-analgesic receptor targets and recurrence/metastasis, using a repository of breast cancer gene expression and matching clinical data. A list of 23 genes encoding for the most prominent anaesthetic-analgesic receptor targets was compiled. This was processed through BreastMark- an algorithm integrating gene expression data from ~17,000 samples and clinical data from >4,500 breast cancer samples. Gene expression data was dichotomized using disease-free survival (survival without recurrence) and distant disease-free survival (survival without metastasis) as end points. Hazard ratios were calculated by Cox-regression analysis. Enrichment for prognostic markers was determined by randomly choosing 23-member gene lists from all available genes, calculating how often >5 significant markers were observed and adjusting p-values for multiple testing. This was repeated 10,000 times and an empirical p-value calculated. Of 23 selected genes, 9 were significantly associated with altered rates of metastasis and 4 with recurrence on univariate analysis. Adjusting for multiple testing, 5 of these 9 genes remained significantly associated with metastasis, non with recurrence. This ratio of genes (5/23) was not significantly enriched for markers of metastasis (p = 0.07). Several anaesthetic-analgesic receptor genes were associated with metastatic spread in breast cancer. Overall there was no significant enrichment in prognostic markers of metastasis, although a trend was observed.
Shao, Shuhong; Li, Zunling; Gao, Wei; Yu, Guohua; Liu, Dexiang; Pan, Fang
2014-01-01
Small cell lung cancer (SCLC) is highly aggressive and is characterized by malignant metastasis. Approximately 90% of patients die due to extensive metastasis. The extracellular matrix (ECM) is a natural barrier that can prevent cellular invasion and metastasis. Therefore, degradation of the ECM must take place in order for extensive metastasis to occur. A disintegrin and metalloprotease (ADAM) is a multi-domain protease that plays an important role in tumorigenesis, as well as tumor development, invasion and metastasis. However, there have been few reports on the expression and role of ADAMs in SCLC. In the current study, the expression and role of ADAMs in SCLC proliferation, invasion and metastasis was investigated. A total of 150 SCLC tissue samples were examined by immunohistochemistry for ADAMs expression. ADAM-12 was found to be abundantly expressed in 72.67% samples and other ADAMs were found to be expressed in 10% to 40% of samples. ADAM-12 levels in serum and urine, from 70 SCLC patients and 40 normal controls, were also measured using ELISA. ADAM-12 expression was significantly higher in SCLC patients than in healthy controls and in patients with extensive disease compared to those with more limited disease. Silencing the expression of ADAM-12 in H1688 cells through the use of specific siRNA significantly reduced cellular proliferation, invasion and metastasis. Supplementing the expression of ADAM-12-L or -S in H345 cells, significantly enhanced cellular proliferation, invasion and metastasis. Animal models with metastatic SCLC also exhibited increased expression of ADAM-12 along with enhanced invasion and metastasis. In brief, ADAM-12 is an independent prognostic factor and diagnostic marker, and is involved in the proliferation, invasion and metastasis of SCLC. PMID:24465799
Yang, Zhen; Garcia, Anapatricia; Xu, Songli; Powell, Doris R.; Vertino, Paula M.; Singh, Shivendra; Marcus, Adam I.
2013-01-01
Though clinicians can predict which patients are at risk for developing metastases, traditional therapies often prove ineffective and metastatic disease is the primary cause of cancer patient death; therefore, there is a need to develop anti-metastatic therapies that can be administered over long durations to specifically inhibit the motility of cancer cells. Withania somnifera root extracts (WRE) have anti-proliferative activity and the active component, Withaferin A, inhibits the pro-metastatic protein, vimentin. Vimentin is an intermediate filament protein and is part of the epithelial to mesenchymal transition (EMT) program to promote metastasis. Here, we determined whether WRE standardized to Withaferin A (sWRE) possesses anti-metastatic activity and whether it inhibits cancer motility via inhibition of vimentin and the EMT program. Several formulations of sWRE were created to enrich for Withaferin A and a stock solution of sWRE in EtOH could recover over 90% of the Withaferin A found in the original extract powder. This sWRE formulation inhibited breast cancer cell motility and invasion at concentrations less than 1µM while having negligible cytotoxicity at this dose. sWRE treatment disrupted vimentin morphology in cell lines, confirming its vimentin inhibitory activity. To determine if sWRE inhibited EMT, TGF-β was used to induce EMT in MCF10A human mammary epithelial cells. In this case, sWRE prevented EMT induction and inhibited 3-D spheroid invasion. These studies were taken into a human xenograft and mouse mammary carcinoma model. In both models, sWRE and Withaferin A showed dose-dependent inhibition of tumor growth and metastatic lung nodule formation with minimal systemic toxicity. Taken together, these data support the hypothesis that low concentrations of sWRE inhibit cancer metastasis potentially through EMT inhibition. Moreover, these doses of sWRE have nearly no toxicity in normal mouse organs, suggesting the potential for clinical use of orally administered WRE capsules. PMID:24069380
Qu, Hai-Xia; Zhao, Li-Ping; Zhan, Shu-Hui; Geng, Chang-Xin; Xu, Lin; Xin, Yong-Ning; Jiang, Xiang-Jun
2016-11-01
The clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. To investigate this question, we conducted a meta-analysis. A comprehensive literature search of electronic databases (up to July 10, 2016) was performed for relevant studies using multiple search strategies. Correlation between PD-L1 expression and clinicopathological features/overall survival (OS) was analyzed. A total of 1,350 ESCC patients from eight studies were included. The pooled odds ratios (ORs) indicated that none of the clinicopathological characteristics was correlated with PD-L1 expression, including gender [OR =0.84; 95% confidence interval (CI): 0.59-1.18; P=0.31], histological differentiation (OR =1.33; 95% CI: 0.95-1.85; P=0.09), tumor depth (OR =0.66; 95% CI: 0.33-1.35; P=0.26), status of lymph node metastasis (OR =0.67; 95% CI: 0.30-1.52; P=0.34), distal metastasis (OR =0.66; 95% CI: 0.40-1.09; P=0.10) and tumor node metastasis (TNM) stage (OR =0.93; 95% CI: 0.49-1.75; P=0.82). The combined hazard ratio (HR) for OS showed a trend that overexpression of PD-L1 might be associated with the survival outcome of ESCC, though the difference was not statistically significant (HR =1.65; 95% CI 0.95-2.85; P=0.07). Based on the published studies, PD-L1 overexpression in ESCC was not associated with common clinicopathological characteristics. PD-L1 might be a poor prognostic biomarker for ESCC. Further large-scale research should be performed to reveal the precise clinicopathological and prognostic significance of PD-L1 in ESCC by unified testing standard.
Advanced Autonomous Systems for Space Operations
NASA Astrophysics Data System (ADS)
Gross, A. R.; Smith, B. D.; Muscettola, N.; Barrett, A.; Mjolssness, E.; Clancy, D. J.
2002-01-01
New missions of exploration and space operations will require unprecedented levels of autonomy to successfully accomplish their objectives. Inherently high levels of complexity, cost, and communication distances will preclude the degree of human involvement common to current and previous space flight missions. With exponentially increasing capabilities of computer hardware and software, including networks and communication systems, a new balance of work is being developed between humans and machines. This new balance holds the promise of not only meeting the greatly increased space exploration requirements, but simultaneously dramatically reducing the design, development, test, and operating costs. New information technologies, which take advantage of knowledge-based software, model-based reasoning, and high performance computer systems, will enable the development of a new generation of design and development tools, schedulers, and vehicle and system health management capabilities. Such tools will provide a degree of machine intelligence and associated autonomy that has previously been unavailable. These capabilities are critical to the future of advanced space operations, since the science and operational requirements specified by such missions, as well as the budgetary constraints will limit the current practice of monitoring and controlling missions by a standing army of ground-based controllers. System autonomy capabilities have made great strides in recent years, for both ground and space flight applications. Autonomous systems have flown on advanced spacecraft, providing new levels of spacecraft capability and mission safety. Such on-board systems operate by utilizing model-based reasoning that provides the capability to work from high-level mission goals, while deriving the detailed system commands internally, rather than having to have such commands transmitted from Earth. This enables missions of such complexity and communication` distances as are not otherwise possible, as well as many more efficient and low cost applications. In addition, utilizing component and system modeling and reasoning capabilities, autonomous systems will play an increasing role in ground operations for space missions, where they will both reduce the human workload as well as provide greater levels of monitoring and system safety. This paper will focus specifically on new and innovative software for remote, autonomous, space systems flight operations. Topics to be presented will include a brief description of key autonomous control concepts, the Remote Agent program that commanded the Deep Space 1 spacecraft to new levels of system autonomy, recent advances in distributed autonomous system capabilities, and concepts for autonomous vehicle health management systems. A brief description of teaming spacecraft and rovers for complex exploration missions will also be provided. New on-board software for autonomous science data acquisition for planetary exploration will be described, as well as advanced systems for safe planetary landings. A new multi-agent architecture that addresses some of the challenges of autonomous systems will be presented. Autonomous operation of ground systems will also be considered, including software for autonomous in-situ propellant production and management, and closed- loop ecological life support systems (CELSS). Finally, plans and directions for the future will be discussed.
DCB - Tumor Metastasis Research
Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.
Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.
Jin, Yun; Ai, Junhua; Shi, Jun
2015-01-01
Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.
Wang, Min-Cong; Jiao, Min; Wu, Tao; Jing, Li; Cui, Jie; Guo, Hui; Tian, Tao; Ruan, Zhi-ping; Wei, Yong-Chang; Jiang, Li-Li; Sun, Hai-Feng; Huang, Lan-Xuan; Nan, Ke-Jun; Li, Chun-Li
2016-01-01
Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI-1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis. PMID:26840020
Osaki, Mitsuhiko; Takeshita, Fumitaka; Sugimoto, Yui; Kosaka, Nobuyoshi; Yamamoto, Yusuke; Yoshioka, Yusuke; Kobayashi, Eisuke; Yamada, Tesshi; Kawai, Akira; Inoue, Toshiaki; Ito, Hisao; Oshimura, Mitsuo; Ochiya, Takahiro
2011-01-01
Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell proliferation. Noninvasive optical imaging technologies revealed that intravenous injection of miR-143, but not negative control miRNA, significantly suppressed lung metastasis of 143B (P < 0.01). To search for miR-143 target mRNA in 143B, microarray analyses were performed using an independent RNA pool extracted by two different comprehensive miR-143-target mRNA collecting systems. Western blot analyses revealed that MMP-13 was mostly protein downregulated by miR-143. Immunohistochemistry using clinical samples clearly revealed MMP-13-positive cells in lung metastasis-positive cases, but not in at least three cases showing higher miR-143 expression in the no metastasis group. Taken together, these data indicated that the downregulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 upregulation, suggesting that miRNA could be used to develop new molecular targets for osteosarcoma metastasis. PMID:21427707
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong
Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cellsmore » and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.« less
Li, Haifeng; Liao, Xiaoying; Liu, Yeqing; Shen, Zhuojian; Gan, Xiangfeng; Li, Haigang; Huang, Zhiquan
2015-11-01
The objective of this study was to investigate the relationship between metastasis-associated in colon cancer-1 and patient clinical characteristics. We also examined the role of metastasis-associated in colon cancer-1 in the proliferation and apoptosis in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 expression was analysed in 65 paraffin-embedded tissue specimens of salivary adenoid cystic carcinoma and 25 adjacent non-cancerous tissues by immunohistochemistry (IHC). We used RNA interference technology to silence metastasis-associated in colon cancer-1 expression in ACCM cells. Cell Counting Kit-8 tests, transwell experiments and flow cytometry were used to test the proliferation, cisplatin resistance, migration, invasion and apoptosis of ACCM cells. Metastasis-associated in colon cancer-1 nuclear and cytoplasmic expression in salivary adenoid cystic carcinoma tissue was higher than in the adjacent normal salivary tissue. The expression level was closely associated with tumour histological grading, perineural invasion and surrounding tumour invasion. The downregulation of metastasis-associated in colon cancer-1 expression inhibited proliferation and induced apoptosis in ACCM cells. The knock-down of metastasis-associated in colon cancer-1 expression had no effect on migration, invasion and chemoresistance. Metastasis-associated in colon cancer-1 may have an important role in tumour development in adenoid cystic carcinoma. Metastasis-associated in colon cancer-1 is a potential biomarker for adenoid cystic carcinoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming
2017-04-18
Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).
Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming
2017-01-01
Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2− occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05). PMID:28038448
Achieving integrated convoys: cargo unmanned ground vehicle development and experimentation
NASA Astrophysics Data System (ADS)
Zych, Noah; Silver, David; Stager, David; Green, Colin; Pilarski, Thomas; Fischer, Jacob
2013-05-01
The Cargo UGV project was initiated in 2010 with the aim of developing and experimenting with advanced autonomous vehicles capable of being integrated unobtrusively into manned logistics convoys. The intent was to validate two hypotheses in complex, operationally representative environments: first, that unmanned tactical wheeled vehicles provide a force protection advantage by creating standoff distance to warfighters during ambushes or improvised explosive device attacks; and second, that these UGVs serve as force multipliers by enabling a single operator to control multiple unmanned assets. To assess whether current state-of-the-art autonomous vehicle technology was sufficiently capable to permit resupply missions to be executed with decreased risk and reduced manpower, and to assess the effect of UGVs on customary convoy tactics, the Marine Corps Warfighting Laboratory and the Joint Ground Robotics Enterprise sponsored Oshkosh Defense and the National Robotics Engineering Center to equip two standard Marine Corps cargo trucks for autonomous operation. This paper details the system architecture, hardware implementation, and software modules developed to meet the vehicle control, perception, and planner requirements compelled by this application. Additionally, the design of a custom human machine interface and an accompanying training program are described, as is the creation of a realistic convoy simulation environment for rapid system development. Finally, results are conveyed from a warfighter experiment in which the effectiveness of the training program for novice operators was assessed, and the impact of the UGVs on convoy operations was observed in a variety of scenarios via direct comparison to a fully manned convoy.
Engineered cell-cell communication via DNA messaging
2012-01-01
Background Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.” Results We have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis. Conclusions We demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia. PMID:22958599
Ground Operations Autonomous Control and Integrated Health Management
NASA Technical Reports Server (NTRS)
Figueroa, Fernando; Walker, Mark; Wilkins, Kim; Johnson, Robert; Sass, Jared; Youney, Justin
2014-01-01
An intelligent autonomous control capability has been developed and is currently being validated in ground cryogenic fluid management operations. The capability embodies a physical architecture consistent with typical launch infrastructure and control systems, augmented by a higher level autonomous control (AC) system enabled to make knowledge-based decisions. The AC system is supported by an integrated system health management (ISHM) capability that detects anomalies, diagnoses causes, determines effects, and could predict future anomalies. AC is implemented using the concept of programmed sequences that could be considered to be building blocks of more generic mission plans. A sequence is a series of steps, and each executes actions once conditions for the step are met (e.g. desired temperatures or fluid state are achieved). For autonomous capability, conditions must consider also health management outcomes, as they will determine whether or not an action is executed, or how an action may be executed, or if an alternative action is executed instead. Aside from health, higher level objectives can also drive how a mission is carried out. The capability was developed using the G2 software environment (www.gensym.com) augmented by a NASA Toolkit that significantly shortens time to deployment. G2 is a commercial product to develop intelligent applications. It is fully object oriented. The core of the capability is a Domain Model of the system where all elements of the system are represented as objects (sensors, instruments, components, pipes, etc.). Reasoning and decision making can be done with all elements in the domain model. The toolkit also enables implementation of failure modes and effects analysis (FMEA), which are represented as root cause trees. FMEA's are programmed graphically, they are reusable, as they address generic FMEA referring to classes of subsystems or objects and their functional relationships. User interfaces for integrated awareness by operators have been created.
NASA Astrophysics Data System (ADS)
Doubleday, J.; Behar, A.; Davies, A.; Mora-Vargas, A.; Tran, D.; Abtahi, A.; Pieri, D. C.; Boudreau, K.; Cecava, J.
2008-12-01
Response time in acquiring sensor data in volcanic emergencies can be greatly improved through use of autonomous systems. For instance, ground-based observations and data processing applications of the JPL Volcano Sensor Web have promptly triggered spacecraft observations [e.g., 1]. The reverse command and information flow path can also be useful, using autonomous analysis of spacecraft data to trigger in situ sensors. In this demonstration project, SO2 sensors were incorporated into expendable "Volcano Monitor" capsules and placed downwind of the Pu'u 'O'o vent of Kilauea volcano, Hawai'i. In nominal (low) power conservation mode, data from these sensors were collected and transmitted every hour to the Volcano Sensor Web through the Iridium Satellite Network. When SO2 readings exceeded a predetermined threshold, the modem within the Volcano Monitor sent an alert to the Sensor Web, and triggered a request for prompt Earth Observing-1 (EO-1) spacecraft data acquisition. The Volcano Monitors were also triggered by the Sensor Web in response to an eruption detection by the MODIS instrument on Terra. During these pre- defined "critical events" the Sensor Web ordered the SO2 sensors within the Volcano Monitor to increase their sampling frequency to every 5 minutes (high power "burst mode"). Autonomous control of the sensors' sampling frequency enabled the Sensor Web to monitor and respond to rapidly evolving conditions, and allowed rapid compilation and dissemination of these data to the scientific community. Reference: [1] Davies et al., (2006) Eos, 87, (1), 1 and 5. This work was performed at the Jet Propulsion Laboratory-California Institute of Technology, under contract to NASA. Support was provided by the NASA AIST program, the Idaho Space Grant Consortium, and the New Mexico Space Grant Program. We also especially thank the personnel of the USGS Hawaiian Volcano Observatory for their invaluable scientific guidance and logistical assistance.
NASA Astrophysics Data System (ADS)
Boudreau, K.; Cecava, J. R.; Behar, A.; Davies, A. G.; Tran, D. Q.; Abtahi, A. A.; Pieri, D. C.; Jpl Volcano Sensor Web Team, A
2007-12-01
Response time in acquiring sensor data in volcanic emergencies can be greatly improved through use of autonomous systems. For instance, ground-based observations and data processing applications of the JPL Volcano Sensor Web have promptly triggered spacecraft observations [e.g., 1]. The reverse command and information flow path can also be useful, using autonomous analysis of spacecraft data to trigger in situ sensors. In this demonstration project, SO2 sensors have been incorporated into expendable "Volcano Monitor" capsules to be placed downwind of the Pu'U 'O'o vent of Kilauea volcano, Hawai'i. In nominal (low) power conservation mode, data from these sensors are collected and transmitted every hour to the Volcano Sensor Web through the Iridium Satellite Network. If SO2 readings exceed a predetermined threshold, the modem within the Volcano Monitor sends an alert to the Sensor Web, triggering a request for prompt Earth Observing-1 ( EO-1) spacecraft data acquisition. During pre-defined "critical events" as perceived by multiple sensors (which could include both in situ and spaceborne devices), however, the Sensor Web can order the SO2 sensors within the Volcano Monitor to increase their sampling frequency to once per minute (high power "burst mode"). Autonomous control of the sensors' sampling frequency enables the Sensor Web to monitor and respond to rapidly evolving conditions before and during an eruption, and allows near real-time compilation and dissemination of these data to the scientific community. Reference: [1] Davies et al., (2006) Eos, 87, (1), 1&5. This work was performed at the Jet Propulsion Laboratory-California Institute of Technology, under contract to NASA. Support was provided by the NASA AIST program, the Idaho Space Grant Consortium, and the New Mexico Space Grant Program. We thank the personnel of the USGS Hawaiian Volcano Observatory for their invaluable assistance.
Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer
2014-09-01
outcome of which is still to be determined. 15. SUBJECT TERMS Lung Metastasis, Intravital Imaging , Tumor Immunology, Tumor Microparticles 16. SECURITY...metastatic fitness in the lung. 2) KEYWORDS: Metastasis, Intravital Imaging , Lung, Breast Cancer, 3) ACCOMPLISHMENTS: What were the major goals of the... intravital imaging of Lung Metastasis b) Characterization of Tumor Cell Behavior During Pulmonary Seeding via 2-photon microscopy c) Characterization of
Kimura, Yoshitaka; Inoue, Asuka; Hangai, Sho; Saijo, Shinobu; Negishi, Hideo; Nishio, Junko; Yamasaki, Sho; Iwakura, Yoichiro; Yanai, Hideyuki; Taniguchi, Tadatsugu
2016-12-06
Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells. We provide evidence that Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells, to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells are selectively endowed with Dectin-2-dependent phagocytotic activity, with neither bone marrow-derived macrophages nor alveolar macrophages showing this potential. Concordantly, subcutaneous primary tumor growth and lung metastasis are not affected by the absence of Dectin-2. In addition, macrophage C-type lectin, a CLR known to be complex with Dectin-2, also contributes to the suppression of liver metastasis. Collectively, these results highlight the hitherto poorly understood mechanism of Kupffer cell-mediated control of metastasis that is mediated by the CLR innate receptor family, with implications for the development of anticancer therapy targeting CLRs.
Wang, Po-Shun; Chou, Cheng-Han; Lin, Cheng-Han; Yao, Yun-Chin; Cheng, Hui-Chuan; Li, Hao-Yi; Chuang, Yu-Chung; Yang, Chia-Ning; Ger, Luo-Ping; Chen, Yu-Chia; Lin, Forn-Chia; Shen, Tang-Long; Hsiao, Michael; Lu, Pei-Jung
2018-05-14
Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.
Competition and niche construction in a model of cancer metastasis
Akçay, Erol
2018-01-01
Niche construction theory states that not only does the environment act on populations to generate Darwinian selection, but organisms reciprocally modify the environment and the sources of natural selection. Cancer cells participate in niche construction as they alter their microenvironments and create pre-metastatic niches; in fact, metastasis is a product of niche construction. Here, we present a mathematical model of niche construction and metastasis. Our model contains producers, which pay a cost to contribute to niche construction that benefits all tumor cells, and cheaters, which reap the benefits without paying the cost. We derive expressions for the conditions necessary for metastasis, showing that the establishment of a mutant lineage that promotes metastasis depends on niche construction specificity and strength of interclonal competition. We identify a tension between the arrival and invasion of metastasis-promoting mutants, where tumors composed only of cheaters remain small but are susceptible to invasion whereas larger tumors containing producers may be unable to facilitate metastasis depending on the level of niche construction specificity. Our results indicate that even if metastatic subclones arise through mutation, metastasis may be hindered by interclonal competition, providing a potential explanation for recent surprising findings that most metastases are derived from early mutants in primary tumors. PMID:29813117
Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis
Crawford, Nigel P. S; Qian, Xiaolan; Ziogas, Argyrios; Papageorge, Alex G; Boersma, Brenda J; Walker, Renard C; Lukes, Luanne; Rowe, William L; Zhang, Jinghui; Ambs, Stefan; Lowy, Douglas R; Anton-Culver, Hoda; Hunter, Kent W
2007-01-01
A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis. PMID:18081427
Cai, Changjing; Shen, Hong; Liu, Wenqiang; Ma, Junli; Zhang, Yan; Yin, Ling; Li, Jindong; Shen, Liangfang; Zeng, Shan
2017-11-01
Thyroid metastasis from nasopharyngeal carcinoma is rare. Metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes hasn't been reported before. We want to share our experience about the treatment choice. A 27-year-old man was diagnosed with nasopharyngeal nonkeratinizing carcinoma in August 2004. In March 2013 he underwent a thyroid carcinoma radical operation, and histological examination revealed metastasis to the thyroid gland from nasopharyngeal carcinoma. An 18F-FDG-PET/CT scan and biopsy showed metastatic abdominal lymph nodes of nasopharyngeal carcinoma in April 2015. A 27-year-old man was diagnosed with metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes. The patient was treated with concurrent chemotherapy and radiotherapy for nasopharyngeal carcinoma and metastasis to the thyroid gland. The metastases to the abdominal lymph nodes received chemotherapy. After 6 cycles of chemotherapy with gemcitabine, cisplatin, and 5-fluorouracil for metastasis to the abdominal lymph nodes, the patient is currently asymptomatic with stable disease and improved quality of life. The treatment choice for metastasis of nasopharyngeal carcinoma depends on the clinical disease extent, and surgery and/or chemo-radiation therapy must be drafted to the individual patient in order to improve the prognosis and quality of life.
Gastric metastasis of breast cancer: a single centre retrospective study.
Almubarak, Maher M; Laé, Marick; Cacheux, Wulfran; de Cremoux, Patricia; Pierga, Jean-Yves; Reyal, Fabien; Bennett, Simon P; Falcou, Marie-Christine; Salmon, Remy J; Baranger, Bernard; Mariani, Pascale
2011-10-01
Digestive metastasis of breast cancer are rare but when they do occur the stomach is one of the commoner sites. To describe the clinical, endoscopic, pathological features and treatment. 35 cases of gastric metastasis were identified retrospectively between 1980 and 2008. The location of the gastric metastasis was fundus (n=15, 43%), antrum (n=15, 43%) or both (n=5, 14%). The histological subtype of primary breast cancer was invasive lobular carcinoma in 34 patients (97%). Hormonal receptors were positive in 19 out of 24 cases (79%), two out of 22 analysed were HER2 positive (9%). There were 16 (46%) patients with peritoneal carcinosis. The treatment was chemotherapy (n=13, 37%), hormonotherapy (n=2, 6%) or both (n=13, 37%). The 2-year survival rate after gastric metastasis diagnosis was 53% with a median follow up of 31 months [7-84 months]. Ninety-seven percent of gastric metastasis from breast cancers are derived from invasive lobular carcinoma. Seventy-nine percent of these are HER+ and comparison with the original histopathological slides of primary breast carcinoma should be performed to differentiate gastric metastasis from primary gastric carcinoma. Peritoneal carcinomatosis accompanied gastric metastasis in almost half the cases in this series and treatment was generally chemotherapy. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Investigation of the roles of exosomes in colorectal cancer liver metastasis.
Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei
2015-05-01
The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.
Reduced ING1 levels in breast cancer promotes metastasis.
Thakur, Satbir; Singla, Arvind K; Chen, Jie; Tran, Uyen; Yang, Yang; Salazar, Carolina; Magliocco, Anthony; Klimowicz, Alexander; Jirik, Frank; Riabowol, Karl
2014-06-30
INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer.
Collective dynamics of cell migration and cell rearrangements
NASA Astrophysics Data System (ADS)
Kabla, Alexandre
Understanding multicellular processes such as embryo development or cancer metastasis requires to decipher the contributions of local cell autonomous behaviours and long range interactions with the tissue environment. A key question in this context concerns the emergence of large scale coordination in cell behaviours, a requirement for collective cell migration or convergent extension. I will present a few examples where physical and mechanical aspects play a significant role in driving tissue scale dynamics.
[A case of fulminant hepatic failure secondary to hepatic metastasis of small cell lung carcinoma].
Hwang, Young Tae; Shin, Jung Woo; Lee, Jun Ho; Hwang, Dae Sung; Eum, Jun Bum; Choi, Hye Jeong; Park, Neung Hwa
2007-12-01
Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma.
Skeletal metastasis: treatments, mouse models, and the Wnt signaling
Valkenburg, Kenneth C.; Steensma, Matthew R.; Williams, Bart O.; Zhong, Zhendong
2013-01-01
Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments. PMID:23327798
Learning to Heal in a Hellish Landscape
ERIC Educational Resources Information Center
Lloyd, Marion
2005-01-01
Established in 1984 by organizations the Donkey Sanctuary and the International League for the Protection of Horses in conjunction with the National Autonomous University of Mexico's School of Veterinary Medicine, an outreach program seeks to provide veterinary care to animals in suburban underprivileged areas of Mexico City and other urban…
Financing Aboriginal Government: The Case of Canada's Eastern Arctic.
ERIC Educational Resources Information Center
Cozzetto, Don
1992-01-01
Describes financial strategies that promote financial autonomy of Native governments. Discusses the creation of trust funds with cash settlements of land claims, continued program funding by the federal government, and financial training for Native peoples in relation to the Nunavut agreement, which created an autonomous Inuit territory in Canada.…
NASA Technical Reports Server (NTRS)
1979-01-01
Failures and deficiencies in flight programs are reviewed and suggestions are made for avoiding them. The technology development problem areas considered are control configured vehicle design, gyros, solid state star sensors, control instrumentation, tolerant/accomodating control systems, large momentum exchange devices, and autonomous rendezvous and docking.
Code of Federal Regulations, 2013 CFR
2013-10-01
... universities; (b) Hospitals, clinics, or autonomous radiation oncology centers meeting the criteria for major... structure and function; (f) Oncologic pathology; (g) Radiation oncology; (h) Radiobiology; (i) Mathematics; (j) Radiation physics; (k) Radiation protection; (l) Radiation oncology technique; (m) Radiographic...
Code of Federal Regulations, 2014 CFR
2014-10-01
... universities; (b) Hospitals, clinics, or autonomous radiation oncology centers meeting the criteria for major... structure and function; (f) Oncologic pathology; (g) Radiation oncology; (h) Radiobiology; (i) Mathematics; (j) Radiation physics; (k) Radiation protection; (l) Radiation oncology technique; (m) Radiographic...
Code of Federal Regulations, 2012 CFR
2012-10-01
... universities; (b) Hospitals, clinics, or autonomous radiation oncology centers meeting the criteria for major... structure and function; (f) Oncologic pathology; (g) Radiation oncology; (h) Radiobiology; (i) Mathematics; (j) Radiation physics; (k) Radiation protection; (l) Radiation oncology technique; (m) Radiographic...
Code of Federal Regulations, 2011 CFR
2011-10-01
... universities; (b) Hospitals, clinics, or autonomous radiation oncology centers meeting the criteria for major... structure and function; (f) Oncologic pathology; (g) Radiation oncology; (h) Radiobiology; (i) Mathematics; (j) Radiation physics; (k) Radiation protection; (l) Radiation oncology technique; (m) Radiographic...
2010-03-01
allows the programmer to use the English language in an expressive manor while still maintaining the logical structure of a programming language ( Pressman ...and Choudhury Tanzeem. 2000. Face Recognition for Smart Environments, IEEE Computer, pp. 50–55. Pressman , Roger. 2010. Software Engineering A
The social structure of family and farm forestry in Alabama
John Schelhas; Robert Zabawa
2009-01-01
Social research on, and programs for, forest landowners in the United States has tended to view them as individuals, and to be oriented toward transferring new knowledge, technical assistance, fi nancial assistance, and even cultural content to autonomous forest landowners. However, social scientists have long recognized that a great...
Architectural Theory in the Undergraduate Curriculum: A Pedagogical Alternative
ERIC Educational Resources Information Center
Smith, Korydon H.
2013-01-01
The study of architectural theory remains absent from many undergraduate design programs, or, if present, the structure of many curricula place "theory" as an autonomous, peripheral course. Theory, however, as it is in other disciplines, is the foundation of the discipline of architecture. To regain the importance and vitality of…
ERIC Educational Resources Information Center
Bowman, Thomas G.; Mazerolle, Stephanie M.; Barrett, Jessica L.
2017-01-01
Context: Athletic training students' ability to transition into professional practice is a critical component for the future of the profession. However, research on professional master's students' transition to practice and readiness to provide autonomous care is lacking. Objective: To determine professional master's athletic training students'…
Knowledge Acquisition, Knowledge Programming, and Knowledge Refinement.
ERIC Educational Resources Information Center
Hayes-Roth, Frederick; And Others
This report describes the principal findings and recommendations of a 2-year Rand research project on machine-aided knowledge acquisition and discusses the transfer of expertise from humans to machines, as well as the functions of planning, debugging, knowledge refinement, and autonomous machine learning. The relative advantages of humans and…
NASA Astrophysics Data System (ADS)
Lang, Á.; Bérczi, Sz.; Szalay, K.; Prajczer, P.; Kocsis, Á.
2014-11-01
We report about the work of the HUSAR-5 groups from the Széchenyi István Gimnázium High School Sopron, Hungary. We build and program robot-rovers, that can autonomous move and measure on a planetary surface.
Current Vocational Training in Latin America.
ERIC Educational Resources Information Center
Alexim, Joao Carlos
Vocational training (VT) programs in Latin America prepare workers to perform middle-level occupations or jobs. VT in Latin America is characterized by the existence of solid and autonomous national institutes linked to the logic of economic production, funded through a payroll levy grant, counting on a tripartite board, and related to ministries…
Research and applications: Artificial intelligence
NASA Technical Reports Server (NTRS)
Chaitin, L. J.; Duda, R. O.; Johanson, P. A.; Raphael, B.; Rosen, C. A.; Yates, R. A.
1970-01-01
The program is reported for developing techniques in artificial intelligence and their application to the control of mobile automatons for carrying out tasks autonomously. Visual scene analysis, short-term problem solving, and long-term problem solving are discussed along with the PDP-15 simulator, LISP-FORTRAN-MACRO interface, resolution strategies, and cost effectiveness.
Gyro and Accelerometer Based Navigation System for a Mobile Autonomous Robot.
1985-12-02
special thanks goes to our thesis advisor Dr. Matthew Kabrisky for having the confidence to turn us loose on this project. Additionally, we would...Wordmaster Word Processor 1 Wordstar Word Processor 1 Virtual Devices Robo A 6802 Cross Assembler 1 Modem 720 Communication Program 1 CP/M Operating
To What Extent Should Schools Be Autonomous?
ERIC Educational Resources Information Center
Goksoy, Suleyman
2014-01-01
The aim of the research is to present school managers' viewpoints about "school autonomy" program in our country and accordingly determine the degree of school managers' autonomy request. The research was made by using scanning method. The research consists of school managers who are working in preschools, elementary schools, secondary…
Interdisciplinary Education and Research in Mexico
ERIC Educational Resources Information Center
Villa-Soto, Juan Carlos
2016-01-01
In this article we discuss interdisciplinary teaching and research in Latin America through the lens of Mexican perspectives, in particular the experiences at the National Autonomous University of Mexico (UNAM). The history of these experiences goes back to the creation of the frst interdisciplinary education programs in Mexico in the 1970s and…
Education in the Rural American Community: A Lifelong Process.
ERIC Educational Resources Information Center
Galbraith, Michael W., Ed.
This book provides a conceptual and practical framework for understanding lifelong education in the context of the multifaceted rural community. The goal of the discussion is to develop educational programs involving new combinations of services and new organizational arrangements so that individuals will become resourceful, autonomous, and…
ERIC Educational Resources Information Center
Steinberg, Matthew P.
2014-01-01
School districts throughout the United States are increasingly providing greater autonomy to local public (non-charter) school principals. In 2005-06, Chicago Public Schools initiated the Autonomous Management and Performance Schools program, granting academic, programmatic, and operational freedoms to select principals. This paper provides…
An XML-Based Mission Command Language for Autonomous Underwater Vehicles (AUVs)
2003-06-01
P. XML: How To Program . Prentice Hall, Inc. Upper Saddle River, New Jersey, 2001 Digital Signature Activity Statement, W3C www.w3.org/Signature...languages because it does not directly specify how information is to be presented, but rather defines the structure (and thus semantics) of the...command and control (C2) aspects of using XML to increase the utility of AUVs. XML programming will be addressed. Current mine warfare doctrine will be
Bayesian Modeling of a Human MMORPG Player
NASA Astrophysics Data System (ADS)
Synnaeve, Gabriel; Bessière, Pierre
2011-03-01
This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.
Tajima, Shogo; Koda, Kenji
2015-01-01
Metastasis rarely occurs in the palatine tonsils. Among primary pulmonary carcinoma subtypes, small cell carcinoma more frequently metastasizes to this site. Herein, we present an exceedingly rare case of a small pulmonary adenocarcinoma that metastasized to the cervical lymph nodes and the right palatine tonsil in a 62-year-old man. In spite of the small size of the primary site, such extensive metastasis may have occurred because of the invasive micropapillary carcinoma pattern seen in the metastatic sites. The manner of metastasis to the palatine tonsil was considered retrograde lymphatic metastasis originating from carcinoma cells in the cervical lymph nodes. Furthermore, Pagetoid spread was observed at the palatine tonsil. Although there have been only a few cases showing retrograde lymphatic metastasis and Pagetoid spread at the metastatic site, we should be careful when speculating about the primary site based on such metastatic sites, especially when dealing with a biopsy sample exhibiting Pagetoid spread.
Genders, Roel E; Osinga, Joris A J; Tromp, Elise E; O'Rourke, Peter; Bouwes Bavinck, Jan N; Plasmeijer, Elsemieke I
2018-06-08
Organ transplant recipients (OTRs) have a high incidence of cutaneous squamous cell carcinoma (cSCC), and immunosuppression has been reported to be an important risk factor for metastasis. The aim of this study was to identify the metastasis risk over a 10-year period for 593 patients with cSCC, of whom 134 were OTR and 459 were immunocompetent. Metastasis incidence rate was 1,046 (95% confidence interval (95% CI) 524-2,096) per 100,000 person years in OTR and 656 (95% CI; 388-1,107) in immunocompetent patients, yielding an incidence rate ratio of 1.6 (95% CI 0.67-3.81). In OTRs head/neck location, older age at transplantation and older age at diagnosis of first cSCC were associated with metastatic risk, and 7 out of 8 metastasized tumours were smaller than 2 cm. In immunocompetent patients tumour size and tumour depth were associated with metastasis. In conclusion, we were not able to demonstrate an increased incidence rate of metastasis in OTRs compared with immunocompetent patients. However, OTRs and immunocompetent patients differed with regard to risk factors for metastasis.
Enomoto, Masaya; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Matsudo, Takaaki; Shigoka, Masatoshi; Enomoto, Masanobu; Ishizaki, Tetsuo; Tsuchida, Akihiko
2017-11-01
A 55-year-old woman underwent laparoscopic anterior resection and D2 lymph node dissection for recto-sigmoid colon cancer in November 2014, which was diagnosed as T3N1M1(H3, PUL2), stage IV , for the purpose of preserving the ileus. FOLFOX therapy with panitumumab(Pmab)was started in January 2015.A t the end of 11 courses, pulmonary metastasis changed to CR, and liver metastasis was down-graded to H2 on the CT.Because of the risk of hepatic dysfunction with advanced fatty liver due to chemotherapy and extrahepatic lesions, we chose radiofrequency ablation(RFA)therapy for liver metastasis.Pmab combined FOLFIRI therapy was administered, and maintenance therapy was initiated.This patient is alive 2 years and 7 months after surgery and 10 months after RFA without relapse.It is suggested that RFA therapy for liver metastasis of colon cancer with pulmonary metastasis combined with chemotherapy could be an effective treatment strategy.
Lee, Ji-Hyung; Jung, Su Myung; Yang, Kyung-Min; Bae, Eunjin; Ahn, Sung Gwe; Park, Jin Seok; Seo, Dongyeob; Kim, Minbeom; Ha, Jihoon; Lee, Jaewon; Kim, Jun-Hyeong; Kim, Jun Hwan; Ooshima, Akira; Park, Jinah; Shin, Donghyuk; Lee, Youn Sook; Lee, Sangho; van Loo, Geert; Jeong, Joon; Kim, Seong-Jin; Park, Seok Hee
2017-10-01
Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.
Bone morphogenetic protein and bone metastasis, implication and therapeutic potential.
Ye, Lin; Mason, Malcolm D; Jiang, Wen G
2011-01-01
Bone metastasis is one of the most common and severe complications in advanced malignancies, particularly in the three leading cancers; breast cancer, prostate cancer and lung cancer. It is currently incurable and causes severe morbidities, including bone pain, hypercalcemia, pathological fracture, spinal cord compression and consequent paralysis. However, the mechanisms underlying the development of bone metastasis remain largely unknown. Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and are pluripotent factors involved in the regulation of embryonic development and postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Since they are potent regulators for bone formation, there is an increasing interest to investigate BMPs and their roles in bone metastasis. BMPs have been implicated in various neoplasms, at both primary and secondary tumors, particularly skeletal metastasis. Recently studies have also suggested that BMP signaling and their antagonists play pivotal roles in bone metastasis. In this review, we discuss the current knowledge of aberrations of BMPs which have been indicated in tumor progression, and particularly in the development of bone metastasis.
Roles of long non-coding RNAs in gastric cancer metastasis
Yang, Zi-Guo; Gao, Ling; Guo, Xiao-Bo; Shi, Yu-Long
2015-01-01
Gastric cancer is the second leading cause of cancer-related deaths. Metastasis, which is an important element of gastric cancer, leads to a high mortality rate and to a poor prognosis. Gastric cancer metastasis has a complex progression that involves multiple biological processes. The comprehensive mechanisms of metastasis remain unclear, though traditional regulation modulates the molecular functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role in different gene regulatory pathways by epigenetic modification and by transcriptional and post-transcription regulation. lncRNAs participate in various diseases, including Alzheimer’s disease, cardiovascular disease, and cancer. The altered expressions of certain lncRNAs are linked to gastric cancer metastasis and invasion, as with tumor suppressor genes or oncogenes. Studies have partly elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their gene regulatory mechanisms. However, comprehensive knowledge regarding the functional mechanisms of gene regulation in metastatic gastric cancer remains scarce. To provide a theoretical basis for therapeutic intervention in metastatic gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles in gastric cancer metastasis. PMID:25954095
Blanco, Mario Andres; Alečković, Maša; Hua, Yuling; Li, Tuo; Wei, Yong; Xu, Zhen; Cristea, Ileana M.; Kang, Yibin
2011-01-01
Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis. PMID:21478147
NASA Astrophysics Data System (ADS)
Cross, J. N.; Meinig, C.; Mordy, C. W.; Lawrence-Slavas, N.; Cokelet, E. D.; Jenkins, R.; Tabisola, H. M.; Stabeno, P. J.
2016-12-01
New autonomous sensors have dramatically increased the resolution and accuracy of oceanographic data collection, enabling rapid sampling over extremely fine scales. Innovative new autonomous platofrms like floats, gliders, drones, and crawling moorings leverage the full potential of these new sensors by extending spatiotemporal reach across varied environments. During 2015 and 2016, The Innovative Technology for Arctic Exploration Program at the Pacific Marine Environmental Laboratory tested several new types of fully autonomous platforms with increased speed, durability, and power and payload capacity designed to deliver cutting-edge ecosystem assessment sensors to remote or inaccessible environments. The Expendable Ice-Tracking (EXIT) gloat developed by the NOAA Pacific Marine Environmental Laboratory (PMEL) is moored near bottom during the ice-free season and released on an autonomous timer beneath the ice during the following winter. The float collects a rapid profile during ascent, and continues to collect critical, poorly-accessible under-ice data until melt, when data is transmitted via satellite. The autonomous Oculus sub-surface glider developed by the University of Washington and PMEL has a large power and payload capacity and an enhanced buoyancy engine. This 'coastal truck' is designed for the rapid water column ascent required by optical imaging systems. The Saildrone is a solar and wind powered ocean unmanned surface vessel (USV) developed by Saildrone, Inc. in partnership with PMEL. This large-payload (200 lbs), fast (1-7 kts), durable (46 kts winds) platform was equipped with 15 sensors designed for ecosystem assessment during 2016, including passive and active acoustic systems specially redesigned for autonomous vehicle deployments. The senors deployed on these platforms achieved rigorous accuracy and precision standards. These innovative platforms provide new sampling capabilities and cost efficiencies in high-resolution sensor deployment, including reconnaissance for annual fisheries and marine mammal surveys; better linkages between sustained observing platforms; and adaptive deployments that can easily target anomalies as they arise.
NASA's computer science research program
NASA Technical Reports Server (NTRS)
Larsen, R. L.
1983-01-01
Following a major assessment of NASA's computing technology needs, a new program of computer science research has been initiated by the Agency. The program includes work in concurrent processing, management of large scale scientific databases, software engineering, reliable computing, and artificial intelligence. The program is driven by applications requirements in computational fluid dynamics, image processing, sensor data management, real-time mission control and autonomous systems. It consists of university research, in-house NASA research, and NASA's Research Institute for Advanced Computer Science (RIACS) and Institute for Computer Applications in Science and Engineering (ICASE). The overall goal is to provide the technical foundation within NASA to exploit advancing computing technology in aerospace applications.
Comprehensive Development Program of Hunter-Killer Peptides for Prostate Cancer
2005-05-01
hydrophobic, and had solubility problems. We then re-designed the peptide as ALLLAIRRR-KKK to increase solubility . Year Abbr. Peptide 3 HP-3 [CNGRC...cell culture experiments confirmed that HK-4 was now soluble , and that we had not lost anti- mitochondria swelling properties, and had in fact gained...the peptides would be expected to inhibit the metastasis of sarcoma and other APN-positive tumor cells. Indeed, the other APN inhibitors, curcumin
Targeting Neuropilin-1 in Prostate Cancer Bone Metastasis
2011-04-01
USA; Dr. Leland W. K. Chung (Email: Leland.Chung@cshs.org), Uro -Oncology Research Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA...Association for Cancer Research Annual Meeting, Los Angeles, CA, 2007. 25 Zhang S, Zhau HE, Iqbal S, Chung LWK, Wu D. Vascular endothelial growth...15. Pedersen LO , Hansen AS, Olsen AC, et al. The interaction between h2-microglobulin (h2m) and puri- fied class-I major histocompatibility (MHC
Resident Preparation for Careers in General Surgery: A Survey of Program Directors.
Cogbill, Thomas H; Klingensmith, Mary E; Jones, Andrew T; Biester, Thomas W; Malangoni, Mark A
2015-01-01
The number of general surgery (GS) residency graduates who choose GS practice has diminished as the popularity of postresidency fellowships has dramatically increased over the past several decades. This study was designed to document current methods of GS preparation during surgery residency and to determine characteristics of programs that produce more graduates who pursue GS practice. An email survey was sent by the American Board of Surgery General Surgery Advisory Committee to program directors of all GS residencies. Program demographic information was procured from the American Board of Surgery database and linked to survey results. Multiple regression was used to predict postresidency choices of graduates. Totally, 252 US allopathic surgical residencies. Totally, 171 residency program directors (68% response rate). The proportion of programs using an emergency/acute care surgery rotation at the main teaching hospital to teach GS increased from 63% in 2003 to 83% in 2014. An autonomous GS outpatient experience was offered in 38% of programs. Practice management curricula were offered in 28% of programs. Institutions with fewer postresidency fellowships (p < 0.003) and fewer surgical specialty residencies (p < 0.036) had a greater percentage of graduates who pursued GS practice. The addition of each fellowship at an institution was associated with a 2% decrease in the number of graduates pursuing GS practice. Residency size was not associated with predilection for fellowship selection and there was no difference between university and independent residencies vis-a-vis the proportion selecting fellowship vs GS practice. Practice management principles and autonomous GS outpatient clinic experiences are offered in a minority of programs. Graduates of programs in institutions with fewer surgery fellowships and residencies are more likely to pursue GS practice. Increased number of postresidency fellowships and specialty residencies may be associated with fewer GS rotations and fewer GS mentors. Further study of these relationships seems warranted. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.
Postdoctoral Fellow | Center for Cancer Research
The Hernandez lab is seeking a postdoctoral fellow to join the research program, which is focused on interrogating the molecular underpinnings of metastatic colonization. The lab utilizes multi-photon intravital microscopy to mechanistically interrogate and visualize the dynamics of metastatic outgrowth, including the roles of supporting stromal and immune cells. The lab has begun pioneering first-ever human tissue models by repurposing perfusion systems to sustain metastasis-bearing tissue (liver and peritoneum) ex vivo. We envision these models will allow us to 1) evaluate putative metastasis governing genes in human tissue, 2) personalize investigation of the metastatic cascade by leveraging multi-photon imaging with an individual patient’s tumor cells, which will be dissociated, labelled, and subsequently injected into the perfusate to seed that patient’s metastatic target tissue, and 3) utilized tumor-bearing tissue as a platform for drug discovery and evaluation of novel drug-delivery combinations. We believe our human tissue models have the potential to transcend multiple disciplines in translational medicine and permit investigations and manipulations not previously possible.