Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

PubMed Central

Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

2015-01-01

Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival.

PubMed

Yang, Jia-Cheng; Risch, Eric; Zhang, Meiqin; Huang, Chan; Huang, Huatian; Lu, Lingeng

2017-09-01

To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. Patients with NSUN2 high IGF-II low had significantly superior overall and disease progression-free survival, followed by NSUN2 low IGF-II low , NSUN2 high IGF-II high and NSUN2 low IGF-II high (p < 0.0001 for overall, p = 0.0024 for progression-free survival, respectively). The associations of NSUN2/IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

Unconditionally Secure Blind Signatures

NASA Astrophysics Data System (ADS)

Hara, Yuki; Seito, Takenobu; Shikata, Junji; Matsumoto, Tsutomu

The blind signature scheme introduced by Chaum allows a user to obtain a valid signature for a message from a signer such that the message is kept secret for the signer. Blind signature schemes have mainly been studied from a viewpoint of computational security so far. In this paper, we study blind signatures in unconditional setting. Specifically, we newly introduce a model of unconditionally secure blind signature schemes (USBS, for short). Also, we propose security notions and their formalization in our model. Finally, we propose a construction method for USBS that is provably secure in our security notions.

Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.

PubMed

Ford, Catriona A; Petrova, Sofia; Pound, John D; Voss, Jorine J L P; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L; Gallimore, Awen M; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E; Dunbar, Donald R; Murray, Paul G; Ruckerl, Dominik; Allen, Judith E; Hume, David A; van Rooijen, Nico; Goodlad, John R; Freeman, Tom C; Gregory, Christopher D

2015-03-02

Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased "in situ transcriptomics" analysis-gene expression profiling of laser-captured TAMs to establish their activation signature in situ-we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of the Euclidean signature in lattice calculations of quasidistributions and other nonlocal matrix elements

NASA Astrophysics Data System (ADS)

Briceño, Raúl A.; Hansen, Maxwell T.; Monahan, Christopher J.

2017-07-01

Lattice quantum chromodynamics (QCD) provides the only known systematic, nonperturbative method for first-principles calculations of nucleon structure. However, for quantities such as light-front parton distribution functions (PDFs) and generalized parton distributions (GPDs), the restriction to Euclidean time prevents direct calculation of the desired observable. Recently, progress has been made in relating these quantities to matrix elements of spatially nonlocal, zero-time operators, referred to as quasidistributions. Still, even for these time-independent matrix elements, potential subtleties have been identified in the role of the Euclidean signature. In this work, we investigate the analytic behavior of spatially nonlocal correlation functions and demonstrate that the matrix elements obtained from Euclidean lattice QCD are identical to those obtained using the Lehmann-Symanzik-Zimmermann reduction formula in Minkowski space. After arguing the equivalence on general grounds, we also show that it holds in a perturbative calculation, where special care is needed to identify the lattice prediction. Finally we present a proof of the uniqueness of the matrix elements obtained from Minkowski and Euclidean correlation functions to all order in perturbation theory.

Drug targeting of NR4A nuclear receptors for treatment of acute myeloid leukemia.

PubMed

Boudreaux, Seth P; Duren, Ryan P; Call, Steven G; Nguyen, Loc; Freire, Pablo R; Narayanan, Padmini; Redell, Michele S; Conneely, Orla M

2018-06-08

NR4As are AML tumor suppressors that are frequently silenced in human acute myeloid leukemia (AML). Despite their potential as novel targets for therapeutic intervention, mechanisms of NR4A silencing and strategies for their reactivation remain poorly defined. Here we show that NR4A silencing in AML occurs through blockade of transcriptional elongation rather than epigenetic promoter silencing. By intersection of NR4A-regulated gene signatures captured upon acute, exogenous expression of NR4As in human AML cells with in silico chemical genomics screening, we identify several FDA-approved drugs including dihydroergotamine (DHE) that reactivate NR4A expression and regulate NR4A-dependent gene signatures. We show that DHE induces NR4A expression via recruitment of the super elongation complex to enable elongation of NR4A promoter paused RNA polymerase II. Finally, DHE exhibits AML selective NR4A-dependent anti-leukemic activity in cytogenetically distinct human AML cells in vitro and delays AML progression in mice revealing its potential as a novel therapeutic agent in AML.

PROSPECT: Profiling of Resistance Patterns Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2011-06-01

8w DC in patients treated with erlotinib, but not sorafenib, indicating that it is not merely a prognostic signature; D) Both the 5-gene signature...disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular signatures in primary tumors...therapeutic strategies at relapse. Specific Aims: Aim 1: To define characteristic TTF/gene expression profiles of prognostically distinct

Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

PubMed

Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

2015-08-03

Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

75 FR 42575 - Electronic Signature and Storage of Form I-9, Employment Eligibility Verification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

... Electronic Signature and Storage of Form I-9, Employment Eligibility Verification AGENCY: U.S. Immigration... published an interim final rule to permit electronic signature and storage of the Form I-9. 71 FR 34510..., or a combination of paper and electronic systems; Employers may change electronic storage systems as...

Development and Validation of a Novel Platform-Independent Metastasis Signature in Human Breast Cancer

PubMed Central

Speers, Corey; Liu, Meilan; Wilder-Romans, Kari; Lawrence, Theodore S.; Pierce, Lori J.; Feng, Felix Y.

2015-01-01

Purpose The molecular drivers of metastasis in breast cancer are not well understood. Therefore, we sought to identify the biological processes underlying distant progression and define a prognostic signature for metastatic potential in breast cancer. Experimental design In vivo screening for metastases was performed using Chick Chorioallantoic Membrane assays in 21 preclinical breast cancer models. Expressed genes associated with metastatic potential were identified using high-throughput analysis. Correlations with biological function were determined using the Database for Annotation, Visualization and Integrated Discovery. Results We identified a broad range of metastatic potential that was independent of intrinsic breast cancer subtypes. 146 genes were significantly associated with metastasis progression and were linked to cancer-related biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and Wnt signaling. These genes were used to develop a platform-independent gene expression signature (M-Sig), which was trained and subsequently validated on 5 independent cohorts totaling nearly 1800 breast cancer patients with all p-values < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate analysis accounting for standard clinicopathologic prognostic variables, M-Sig remained the strongest prognostic factor for metastatic progression, with p-values < 0.001 and hazard ratios > 2 in three different cohorts. Conclusion M-Sig is strongly prognostic for metastatic progression, and may provide clinical utility in combination with treatment prediction tools to better guide patient care. In addition, the platform-independent nature of the signature makes it an excellent research tool as it can be directly applied onto existing, and future, datasets. PMID:25974184

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer.

PubMed

Urbanucci, Alfonso; Barfeld, Stefan J; Kytölä, Ville; Itkonen, Harri M; Coleman, Ilsa M; Vodák, Daniel; Sjöblom, Liisa; Sheng, Xia; Tolonen, Teemu; Minner, Sarah; Burdelski, Christoph; Kivinummi, Kati K; Kohvakka, Annika; Kregel, Steven; Takhar, Mandeep; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Lloyd, Paul; Karnes, R Jeffrey; Ross, Ashley E; Schaeffer, Edward M; Vander Griend, Donald J; Knapp, Stefan; Corey, Eva; Feng, Felix Y; Nelson, Peter S; Saatcioglu, Fahri; Knudsen, Karen E; Tammela, Teuvo L J; Sauter, Guido; Schlomm, Thorsten; Nykter, Matti; Visakorpi, Tapio; Mills, Ian G

2017-06-06

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.

PubMed

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H; Beltran, Himisha; Fox, Archa H; Elemento, Olivier; Rubin, Mark A

2014-11-21

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription.

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

PubMed Central

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S.; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y.; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A.; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B.; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H.; Beltran, Himisha; Fox, Archa H.; Elemento, Olivier; Rubin, Mark A.

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. PMID:25415230

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

PubMed Central

Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

2010-01-01

Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation. PMID:20405009

Biomass power for rural development. Technical progress report, January 1, 1997--March 31, 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

Detailed task progress reports and schedules are provided for the DOE/USDA sponsored Biomass Power for Rural Development project. The focus of the project is on developing commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firingmore » tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC). Phase-II of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is under way. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-III will represent fullscale commercialization of the energy crop and power generation on a sustainable basis.« less

Biomass power for rural development. Technical progress report, April 1, 1997--June 30, 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

Detailed task progress reports and schedules are provided for the DOE/USDA sponsored Biomass Power for Rural Development project. The focus of the project is on developing commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-I, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firingmore » tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC). Phase-H of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is under way. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-III will represent fullscale commercialization of the energy crop and power generation on a sustainable basis.« less

Estimation of fatigue life using electromechanical impedance technique

NASA Astrophysics Data System (ADS)

Lim, Yee Yan; Soh, Chee Kiong

2010-04-01

Fatigue induced damage is often progressive and gradual in nature. Structures subjected to large number of fatigue load cycles will encounter the process of progressive crack initiation, propagation and finally fracture. Monitoring of structural health, especially for the critical components, is therefore essential for early detection of potential harmful crack. Recent advent of smart materials such as piezo-impedance transducer adopting the electromechanical impedance (EMI) technique and wave propagation technique are well proven to be effective in incipient damage detection and characterization. Exceptional advantages such as autonomous, real-time and online, remote monitoring may provide a cost-effective alternative to the conventional structural health monitoring (SHM) techniques. In this study, the main focus is to investigate the feasibility of characterizing a propagating fatigue crack in a structure using the EMI technique as well as estimating its remaining fatigue life using the linear elastic fracture mechanics (LEFM) approach. Uniaxial cyclic tensile load is applied on a lab-sized aluminum beam up to failure. Progressive shift in admittance signatures measured by the piezo-impedance transducer (PZT patch) corresponding to increase of loading cycles reflects effectiveness of the EMI technique in tracing the process of fatigue damage progression. With the use of LEFM, prediction of the remaining life of the structure at different cycles of loading is possible.

Majorana zero modes in superconductor-semiconductor heterostructures

NASA Astrophysics Data System (ADS)

Lutchyn, R. M.; Bakkers, E. P. A. M.; Kouwenhoven, L. P.; Krogstrup, P.; Marcus, C. M.; Oreg, Y.

2018-05-01

Realizing topological superconductivity and Majorana zero modes in the laboratory is a major goal in condensed-matter physics. In this Review, we survey the current status of this rapidly developing field, focusing on proposals for the realization of topological superconductivity in semiconductor-superconductor heterostructures. We examine materials science progress in growing InAs and InSb semiconductor nanowires and characterizing these systems. We then discuss the observation of robust signatures of Majorana zero modes in recent experiments, paying particular attention to zero-bias tunnelling conduction measurements and Coulomb blockade experiments. We also outline several next-generation experiments probing exotic properties of Majorana zero modes, including fusion rules and non-Abelian exchange statistics. Finally, we discuss prospects for implementing Majorana-based topological quantum computation.

A Semi-Supervised Approach for Refining Transcriptional Signatures of Drug Response and Repositioning Predictions

PubMed Central

Iorio, Francesco; Shrestha, Roshan L.; Levin, Nicolas; Boilot, Viviane; Garnett, Mathew J.; Saez-Rodriguez, Julio; Draviam, Viji M.

2015-01-01

We present a novel strategy to identify drug-repositioning opportunities. The starting point of our method is the generation of a signature summarising the consensual transcriptional response of multiple human cell lines to a compound of interest (namely the seed compound). This signature can be derived from data in existing databases, such as the connectivity-map, and it is used at first instance to query a network interlinking all the connectivity-map compounds, based on the similarity of their transcriptional responses. This provides a drug neighbourhood, composed of compounds predicted to share some effects with the seed one. The original signature is then refined by systematically reducing its overlap with the transcriptional responses induced by drugs in this neighbourhood that are known to share a secondary effect with the seed compound. Finally, the drug network is queried again with the resulting refined signatures and the whole process is carried on for a number of iterations. Drugs in the final refined neighbourhood are then predicted to exert the principal mode of action of the seed compound. We illustrate our approach using paclitaxel (a microtubule stabilising agent) as seed compound. Our method predicts that glipizide and splitomicin perturb microtubule function in human cells: a result that could not be obtained through standard signature matching methods. In agreement, we find that glipizide and splitomicin reduce interphase microtubule growth rates and transiently increase the percentage of mitotic cells–consistent with our prediction. Finally, we validated the refined signatures of paclitaxel response by mining a large drug screening dataset, showing that human cancer cell lines whose basal transcriptional profile is anti-correlated to them are significantly more sensitive to paclitaxel and docetaxel. PMID:26452147

Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS.

PubMed

Butovsky, Oleg; Siddiqui, Shafiuddin; Gabriely, Galina; Lanser, Amanda J; Dake, Ben; Murugaiyan, Gopal; Doykan, Camille E; Wu, Pauline M; Gali, Reddy R; Iyer, Lakshmanan K; Lawson, Robert; Berry, James; Krichevsky, Anna M; Cudkowicz, Merit E; Weiner, Howard L

2012-09-01

Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with neuronal cell death that is thought to involve aberrant immune responses. Here we investigated the role of innate immunity in a mouse model of ALS. We found that inflammatory monocytes were activated and that their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We also found a decrease in resident microglia in the spinal cord with disease progression. Prior to disease onset, splenic Ly6Chi monocytes expressed a polarized macrophage phenotype (M1 signature), which included increased levels of chemokine receptor CCR2. As disease onset neared, microglia expressed increased CCL2 and other chemotaxis-associated molecules, which led to the recruitment of monocytes to the CNS by spinal cord-derived microglia. Treatment with anti-Ly6C mAb modulated the Ly6Chi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss, and extended survival. In humans with ALS, the analogous monocytes (CD14+CD16-) exhibited an ALS-specific microRNA inflammatory signature similar to that observed in the ALS mouse model, linking the animal model and the human disease. Thus, the profile of monocytes in ALS patients may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach.

NRF2-regulated metabolic gene signature as a prognostic biomarker in non-small cell lung cancer

PubMed Central

Namani, Akhileshwar; Cui, Qin Qin; Wu, Yihe; Wang, Hongyan; Wang, Xiu Jun; Tang, Xiuwen

2017-01-01

Mutations in Kelch-like ECH-associated protein 1 (KEAP1) cause the aberrant activation of nuclear factor erythroid-derived 2-like 2 (NRF2), which leads to oncogenesis and drug resistance in lung cancer cells. Our study was designed to identify the genes involved in lung cancer progression targeted by NRF2. A series of microarray experiments in normal and cancer cells, as well as in animal models, have revealed regulatory genes downstream of NRF2 that are involved in wide variety of pathways. Specifically, we carried out individual and combinatorial microarray analysis of KEAP1 overexpression and NRF2 siRNA-knockdown in a KEAP1 mutant-A549 non-small cell lung cancer (NSCLC) cell line. As a result, we identified a list of genes which were mainly involved in metabolic functions in NSCLC by using functional annotation analysis. In addition, we carried out in silico analysis to characterize the antioxidant responsive element sequences in the promoter regions of known and putative NRF2-regulated metabolic genes. We further identified an NRF2-regulated metabolic gene signature (NRMGS) by correlating the microarray data with lung adenocarcinoma RNA-Seq gene expression data from The Cancer Genome Atlas followed by qRT-PCR validation, and finally showed that higher expression of the signature conferred a poor prognosis in 8 independent NSCLC cohorts. Our findings provide novel prognostic biomarkers for NSCLC. PMID:29050246

The application of artificial intelligence to microarray data: identification of a novel gene signature to identify bladder cancer progression.

PubMed

Catto, James W F; Abbod, Maysam F; Wild, Peter J; Linkens, Derek A; Pilarsky, Christian; Rehman, Ishtiaq; Rosario, Derek J; Denzinger, Stefan; Burger, Maximilian; Stoehr, Robert; Knuechel, Ruth; Hartmann, Arndt; Hamdy, Freddie C

2010-03-01

New methods for identifying bladder cancer (BCa) progression are required. Gene expression microarrays can reveal insights into disease biology and identify novel biomarkers. However, these experiments produce large datasets that are difficult to interpret. To develop a novel method of microarray analysis combining two forms of artificial intelligence (AI): neurofuzzy modelling (NFM) and artificial neural networks (ANN) and validate it in a BCa cohort. We used AI and statistical analyses to identify progression-related genes in a microarray dataset (n=66 tumours, n=2800 genes). The AI-selected genes were then investigated in a second cohort (n=262 tumours) using immunohistochemistry. We compared the accuracy of AI and statistical approaches to identify tumour progression. AI identified 11 progression-associated genes (odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.56-0.87; p=0.0004), and these were more discriminate than genes chosen using statistical analyses (OR: 1.24; 95% CI, 0.96-1.60; p=0.09). The expression of six AI-selected genes (LIG3, FAS, KRT18, ICAM1, DSG2, and BRCA2) was determined using commercial antibodies and successfully identified tumour progression (concordance index: 0.66; log-rank test: p=0.01). AI-selected genes were more discriminate than pathologic criteria at determining progression (Cox multivariate analysis: p=0.01). Limitations include the use of statistical correlation to identify 200 genes for AI analysis and that we did not compare regression identified genes with immunohistochemistry. AI and statistical analyses use different techniques of inference to determine gene-phenotype associations and identify distinct prognostic gene signatures that are equally valid. We have identified a prognostic gene signature whose members reflect a variety of carcinogenic pathways that could identify progression in non-muscle-invasive BCa. 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

PubMed Central

Chiappini, Franck; Coilly, Audrey; Kadar, Hanane; Gual, Philippe; Tran, Albert; Desterke, Christophe; Samuel, Didier; Duclos-Vallée, Jean-Charles; Touboul, David; Bertrand-Michel, Justine; Brunelle, Alain; Guettier, Catherine; Le Naour, François

2017-01-01

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression. PMID:28436449

New Concepts in Electromagnetic Materials and Antennas

DTIC Science & Technology

2015-01-01

Bae-Ian Wu Antennas & Electromagnetics Technology Branch Multispectral Sensing & Detection Division JANUARY 2015 Final Report...Signature// //Signature// BRADLEY A. KRAMER, Program Manager TONY C. KIM, Branch Chief Antenna & Electromagnetic Technology ...Branch Antenna & Electromagnetic Technology Branch Multispectral Sensing & Detection Division Multispectral Sensing & Detection Division

Progress in interpreting CO2 lidar signatures to obtain cirrus microphysical and optical properties

NASA Technical Reports Server (NTRS)

Eberhard, Wynn L.

1993-01-01

One cloud/radiation issue at FIRE 2 that has been addressed by the CO2 lidar team is the zenith-enhanced backscatter (ZEB) signature from oriented crystals. A second topic is narrow-beam optical depth measurements using CO2 lidar. This paper describes the theoretical models we have developed for these phenomena and the data-processing algorithms derived from them.

Mission Command and JC41: Managing Chaos in a Dynamic World

DTIC Science & Technology

2018-04-20

memorandum, master’s thesis , progress, quarterly, research, special, group study, etc. 3. DATES COVERED. Indicate the time during which the work was...Signature: __________________________ 20 April 2018 Thesis Advisor: Signature: __________________________ Bryon Greenwald, Ph.D., Professor...Jody Owens for their mentorship and critical feedback that proved to be instrumental in writing this thesis . I would be remiss if I failed to thank

Ancient Biomolecules and Evolutionary Inference.

PubMed

Cappellini, Enrico; Prohaska, Ana; Racimo, Fernando; Welker, Frido; Pedersen, Mikkel Winther; Allentoft, Morten E; de Barros Damgaard, Peter; Gutenbrunner, Petra; Dunne, Julie; Hammann, Simon; Roffet-Salque, Mélanie; Ilardo, Melissa; Moreno-Mayar, J Víctor; Wang, Yucheng; Sikora, Martin; Vinner, Lasse; Cox, Jürgen; Evershed, Richard P; Willerslev, Eske

2018-04-25

Over the last decade, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught with many challenges, the field now stands on firm foundations. Researchers now successfully retrieve nucleotide and amino acid sequences, as well as lipid signatures, from progressively older samples, originating from geographic areas and depositional environments that, until recently, were regarded as hostile to long-term preservation of biomolecules. Sampling frequencies and the spatial and temporal scope of studies have also increased markedly, and with them the size and quality of the data sets generated. This progress has been made possible by continuous technical innovations in analytical methods, enhanced criteria for the selection of ancient samples, integrated experimental methods, and advanced computational approaches. Here, we discuss the history and current state of ancient biomolecule research, its applications to evolutionary inference, and future directions for this young and exciting field. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Public-key quantum digital signature scheme with one-time pad private-key

NASA Astrophysics Data System (ADS)

Chen, Feng-Lin; Liu, Wan-Fang; Chen, Su-Gen; Wang, Zhi-Hua

2018-01-01

A quantum digital signature scheme is firstly proposed based on public-key quantum cryptosystem. In the scheme, the verification public-key is derived from the signer's identity information (such as e-mail) on the foundation of identity-based encryption, and the signature private-key is generated by one-time pad (OTP) protocol. The public-key and private-key pair belongs to classical bits, but the signature cipher belongs to quantum qubits. After the signer announces the public-key and generates the final quantum signature, each verifier can verify publicly whether the signature is valid or not with the public-key and quantum digital digest. Analysis results show that the proposed scheme satisfies non-repudiation and unforgeability. Information-theoretic security of the scheme is ensured by quantum indistinguishability mechanics and OTP protocol. Based on the public-key cryptosystem, the proposed scheme is easier to be realized compared with other quantum signature schemes under current technical conditions.

Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.

PubMed

Knutson, Todd P; Daniel, Andrea R; Fan, Danhua; Silverstein, Kevin At; Covington, Kyle R; Fuqua, Suzanne Aw; Lange, Carol A

2012-06-14

Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2). Phospho-Ser294 PRs are resistant to ligand-dependent Lys388 SUMOylation (that is, a repressive modification). Antagonism of PR small ubiquitin-like modifier (SUMO)ylation by mitogenic protein kinases suggests a mechanism for derepression (that is, transcriptional activation) of target genes. As a broad range of PR protein expression is observed clinically, a PR gene signature would provide a valuable marker of PR contribution to early breast cancer progression. Global gene expression patterns were measured in T47D and MCF-7 breast cancer cells expressing either wild-type (SUMOylation-capable) or K388R (SUMOylation-deficient) PRs and subjected to pathway analysis. Gene sets were validated by RT-qPCR. Recruitment of coregulators and histone methylation levels were determined by chromatin immunoprecipitation. Changes in cell proliferation and survival were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and western blotting. Finally, human breast tumor cohort datasets were probed to identify PR-associated gene signatures; metagene analysis was employed to define survival rates in patients whose tumors express a PR gene signature. 'SUMO-sensitive' PR target genes primarily include genes required for proliferative and pro-survival signaling. DeSUMOylated K388R receptors are preferentially recruited to enhancer regions of derepressed genes (that is, MSX2, RGS2, MAP1A, and PDK4) with the steroid receptor coactivator, CREB-(cAMP-response element-binding protein)-binding protein (CBP), and mixed lineage leukemia 2 (MLL2), a histone methyltransferase mediator of nucleosome remodeling. PR SUMOylation blocks these events, suggesting that SUMO modification of PR prevents interactions with mediators of early chromatin remodeling at 'closed' enhancer regions. SUMO-deficient (phospho-Ser294) PR gene signatures are significantly associated with human epidermal growth factor 2 (ERBB2)-positive luminal breast tumors and predictive of early metastasis and shortened survival. Treatment with antiprogestin or MEK inhibitor abrogated expression of SUMO-sensitive PR target-genes and inhibited proliferation in BT-474 (estrogen receptor (ER)+/PR+/ERBB2+) breast cancer cells. We conclude that reversible PR SUMOylation/deSUMOylation profoundly alters target gene selection in breast cancer cells. Phosphorylation-induced PR deSUMOylation favors a permissive chromatin environment via recruitment of CBP and MLL2. Patients whose ER+/PR+ tumors are driven by hyperactive (that is, derepressed) phospho-PRs may benefit from endocrine (antiestrogen) therapies that contain an antiprogestin.

Secure quantum signatures: a practical quantum technology (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andersson, Erika

2016-10-01

Modern cryptography encompasses much more than encryption of secret messages. Signature schemes are widely used to guarantee that messages cannot be forged or tampered with, for example in e-mail, software updates and electronic commerce. Messages are also transferrable, which distinguishes digital signatures from message authentication. Transferability means that messages can be forwarded; in other words, that a sender is unlikely to be able to make one recipient accept a message which is subsequently rejected by another recipient if the message is forwarded. Similar to public-key encryption, the security of commonly used signature schemes relies on the assumed computational difficulty of problems such as finding discrete logarithms or factoring large primes. With quantum computers, such assumptions would no longer be valid. Partly for this reason, it is desirable to develop signature schemes with unconditional or information-theoretic security. Quantum signature schemes are one possible solution. Similar to quantum key distribution (QKD), their unconditional security relies only on the laws of quantum mechanics. Quantum signatures can be realized with the same system components as QKD, but are so far less investigated. This talk aims to provide an introduction to quantum signatures and to review theoretical and experimental progress so far.

Distinct microbiological signatures associated with triple negative breast cancer.

PubMed

Banerjee, Sagarika; Wei, Zhi; Tan, Fei; Peck, Kristen N; Shih, Natalie; Feldman, Michael; Rebbeck, Timothy R; Alwine, James C; Robertson, Erle S

2015-10-15

Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

Spectral signatures for RDX-based explosives in the 3 micron region

NASA Astrophysics Data System (ADS)

Osborn, Tabetha; Kaimal, Sindhu; Reeve, Scott W.; Burns, William

2008-04-01

Explosive compounds such as RDX, and HMX present significant challenges to optically based sensors. This difficulty is due in part to the low vapor pressures these compounds possess. One approach for sensing explosives that circumvents the low explosive vapor pressure problem, involves focusing on the trace amounts of relatively high vapor pressure impurities that will be present in the vapor signature. In order to effectively detect these volatile impurities, the spectral signature databases must be readily available. One of our goals therefore, is the generation of a database of high resolution spectral signatures for these volatile organic impurities. Some rather formidable spectroscopic measurement challenges have been encountered while working to extend the spectral signature effort to the 3 micron region. Here we will outline progress to date, with a focus on the volatile organic compounds formaldehyde, acetaldehyde, nitromethane, acetone, isobutene, and cyclohexanone.

Modeling the Lexical Morphology of Western Handwritten Signatures

PubMed Central

Diaz-Cabrera, Moises; Ferrer, Miguel A.; Morales, Aythami

2015-01-01

A handwritten signature is the final response to a complex cognitive and neuromuscular process which is the result of the learning process. Because of the many factors involved in signing, it is possible to study the signature from many points of view: graphologists, forensic experts, neurologists and computer vision experts have all examined them. Researchers study written signatures for psychiatric, penal, health and automatic verification purposes. As a potentially useful, multi-purpose study, this paper is focused on the lexical morphology of handwritten signatures. This we understand to mean the identification, analysis, and description of the signature structures of a given signer. In this work we analyze different public datasets involving 1533 signers from different Western geographical areas. Some relevant characteristics of signature lexical morphology have been selected, examined in terms of their probability distribution functions and modeled through a General Extreme Value distribution. This study suggests some useful models for multi-disciplinary sciences which depend on handwriting signatures. PMID:25860942

Collaborative Research and Development (CR&D) III Task Order 0077: Fundamental Studies of Plasticity, Interfacial Boundaries and Liquid Metals

DTIC Science & Technology

2013-06-01

Interfacial Boundaries and Liquid Metals Dallas Trinkle Independent Contractor JUNE 2013 Final Report Approved for public...SIGNATURE//_________________ CHRISTOPHER WOODWARD, Project Engineer DANIEL EVANS, Chief Metals Branch Metals Branch Structural ...Materials Division Structural Materials Division ____//SIGNATURE//___________________ ROBERT T. MARSHALL, Deputy Chief

Processes of arroyo filling in northern New Mexico, USA

USGS Publications Warehouse

Friedman, Jonathan M.; Vincent, Kirk R.; Griffin, Eleanor R.; Scott, Michael L.; Shafroth, Patrick B.; Auble, Gregor T.

2015-01-01

We documented arroyo evolution at the tree, trench, and arroyo scales along the lower Rio Puerco and Chaco Wash in northern New Mexico, USA. We excavated 29 buried living woody plants and used burial signatures in their annual rings to date stratigraphy in four trenches across the arroyos. Then, we reconstructed the history of arroyo evolution by combining trench data with arroyo-scale information from aerial imagery, light detection and ranging (LiDAR), longitudinal profiles, and repeat surveys of cross sections. Burial signatures in annual rings of salt cedar and willow dated sedimentary beds greater than 30 cm thick with annual precision. Along both arroyos, incision occurred until the 1930s in association with extreme high flows, and subsequent filling involved vegetation development, channel narrowing, increased sinuosity, and finally vertical aggradation. A strongly depositional sediment transport regime interacted with floodplain shrubs to produce a characteristic narrow, trapezoidal channel. The 55 km study reach along the Rio Puerco demonstrated upstream progression of arroyo widening and filling, but not of arroyo incision, channel narrowing, or floodplain vegetation development. We conclude that the occurrence of upstream progression within large basins like the Rio Puerco makes precise synchrony across basins impossible. Arroyo wall retreat is now mostly limited to locations where meanders impinge on the arroyo wall, forming hairpin bends, for which entry to and exit from the wall are stationary. Average annual sediment storage within the Rio Puerco study reach between 1955 and 2005 was 4.8 × 105 t/yr, 16% of the average annual suspended sediment yield, and 24% of the long-term bedrock denudation rate. At this rate, the arroyo would fill in 310 yr.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

PubMed

Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R; Altieri, Dario C; Vaira, Valentina; Bosari, Silvano

2015-01-01

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

A prospective blood RNA signature for tuberculosis disease risk

PubMed Central

Zak, Daniel E.; Penn-Nicholson, Adam; Scriba, Thomas J.; Thompson, Ethan; Suliman, Sara; Amon, Lynn M.; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Hussey, Gregory D.; Abrahams, Deborah; Kafaar, Fazlin; Hawkridge, Tony; Verver, Suzanne; Hughes, E. Jane; Ota, Martin; Sutherland, Jayne; Howe, Rawleigh; Dockrell, Hazel M.; Boom, W. Henry; Thiel, Bonnie; Ottenhoff, Tom H.M.; Mayanja-Kizza, Harriet; Crampin, Amelia C; Downing, Katrina; Hatherill, Mark; Valvo, Joe; Shankar, Smitha; Parida, Shreemanta K; Kaufmann, Stefan H.E.; Walzl, Gerhard; Aderem, Alan; Hanekom, Willem A.

2016-01-01

Background Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease may lead to interventions that impact the epidemic. Methods Healthy, M. tuberculosis infected South African adolescents were followed for 2 years; blood was collected every 6 months. A prospective signature of risk was derived from whole blood RNA-Sequencing data by comparing participants who ultimately developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. The latter participants were household contacts of adults with active pulmonary tuberculosis disease. Findings Of 6,363 adolescents screened, 46 progressors and 107 matched controls were identified. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% confidence interval, 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA-Seq and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation The whole blood tuberculosis risk signature prospectively identified persons at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill and Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union and the South African Medical Research Council (detail at end of text). PMID:27017310

SABRE observations of Pi2 pulsations: case studies

NASA Astrophysics Data System (ADS)

Bradshaw, E. G.; Lester, M.

1997-01-01

The characteristics of substorm-associated Pi2 pulsations observed by the SABRE coherent radar system during three separate case studies are presented. The SABRE field of view is well positioned to observe the differences between the auroral zone pulsation signature and that observed at mid-latitudes. During the first case study the SABRE field of view is initially in the eastward electrojet, equatorward and to the west of the substorm-enhanced electrojet current. As the interval progresses, the western, upward field-aligned current of the substorm current wedge moves westward across the longitudes of the radar field of view. The westward motion of the wedge is apparent in the spatial and temporal signatures of the associated Pi2 pulsation spectra and polarisation sense. During the second case study, the complex field-aligned and ionospheric currents associated with the pulsation generation region move equatorward into the SABRE field of view and then poleward out of it again after the third pulsation in the series. The spectral content of the four pulsations during the interval indicate different auroral zone and mid-latitude signatures. The final case study is from a period of low magnetic activity when SABRE observes a Pi2 pulsation signature from regions equatorward of the enhanced substorm currents. There is an apparent mode change between the signature observed by SABRE in the ionosphere and that on the ground by magnetometers at latitudes slightly equatorward of the radar field of view. The observations are discussed in terms of published theories of the generation mechanisms for this type of pulsation. Different signatures are observed by SABRE depending on the level of magnetic activity and the position of the SABRE field of view relative to the pulsation generation region. A twin source model for Pi2 pulsation generation provides the clearest explanation of the signatures observed Acknowledgements. The authors are grateful to Prof. D. J. Southwood (Imperial College, London), J. C. Samson (University of Alberta, Edmonton), L. J. Lanzerotti (AT&T Bell Laboratories), A. Wolfe (New York City Technical College) and to Dr. M. Vellante (University of LÁquila) for helpful discussions. They also thank Dr. A. Meloni (Istituto Nazionale di Geofisica, Roma) who made available geomagnetic field observations from LÁquila Geomagnetic Observatory. This research activity at LÁquila is supported by MURST (40% and 60% contracts) and by GIFCO/CNR. Topical Editor K.-H. Glaßmeier thanks C. Waters and S. Fujita for their help in evaluating this paper.-> Correspondence to :P. Francia->

Role of HGF in epithelial–stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ

PubMed Central

2013-01-01

Introduction Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how stromal–epithelial interactions evolve in benign and pre-invasive lesions. Methods To study epithelial–stromal interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and MCF10AT1). Relevant pathways were then evaluated in vivo for associations with basal-like subtype and were targeted in vitro to evaluate effects on morphogenesis. Results Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulated the HGF receptor MET. In three-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with the basal-like subtype, with approximately 86% of basal-like cancers highly expressing the HGF signature, and because high expression of HGF signature was associated with poor survival. Conclusions Coordinated and complementary changes in HGF/MET expression occur in epithelium and stroma during progression of pre-invasive basal-like lesions. These results suggest that targeting stroma-derived HGF signaling in early carcinogenesis may block progression of basal-like precursor lesions. PMID:24025166

Searches for dark matter and new physics with unconventional signatures

NASA Astrophysics Data System (ADS)

Wulz, C.-E.; CMS Collaboration

2017-07-01

Selected results on searches for dark matter and unconventional signatures with the CMS detector are presented. Dark matter searches in channels with one or two jets, single photons, vector bosons, or top and bottom quarks combined with missing momentum in the final states are described. Unusual signatures such as displaced objects, disappearing or kinked tracks, delayed or stopped particles have also been explored. The analyses were performed with proton-proton data recorded at LHC centre-of-mass energies up to 13TeV.

Binary neutron star mergers: a review of Einstein's richest laboratory.

PubMed

Baiotti, Luca; Rezzolla, Luciano

2017-09-01

In a single process, the merger of binary neutron star systems combines extreme gravity, the copious emission of gravitational waves, complex microphysics and electromagnetic processes, which can lead to astrophysical signatures observable at the largest redshifts. We review here the recent progress in understanding what could be considered Einstein's richest laboratory, highlighting in particular the numerous significant advances of the last decade. Although special attention is paid to the status of models, techniques and results for fully general-relativistic dynamical simulations, a review is also offered on the initial data and advanced simulations with approximate treatments of gravity. Finally, we review the considerable amount of work carried out on the post-merger phase, including black-hole formation, torus accretion onto the merged compact object, the connection with gamma-ray burst engines, ejected material, and its nucleosynthesis.

Binary neutron star mergers: a review of Einstein’s richest laboratory

NASA Astrophysics Data System (ADS)

Baiotti, Luca; Rezzolla, Luciano

2017-09-01

In a single process, the merger of binary neutron star systems combines extreme gravity, the copious emission of gravitational waves, complex microphysics and electromagnetic processes, which can lead to astrophysical signatures observable at the largest redshifts. We review here the recent progress in understanding what could be considered Einstein’s richest laboratory, highlighting in particular the numerous significant advances of the last decade. Although special attention is paid to the status of models, techniques and results for fully general-relativistic dynamical simulations, a review is also offered on the initial data and advanced simulations with approximate treatments of gravity. Finally, we review the considerable amount of work carried out on the post-merger phase, including black-hole formation, torus accretion onto the merged compact object, the connection with gamma-ray burst engines, ejected material, and its nucleosynthesis.

Boost-phase discrimination research

NASA Technical Reports Server (NTRS)

Langhoff, Stephen R.; Feiereisen, William J.

1993-01-01

The final report describes the combined work of the Computational Chemistry and Aerothermodynamics branches within the Thermosciences Division at NASA Ames Research Center directed at understanding the signatures of shock-heated air. Considerable progress was made in determining accurate transition probabilities for the important band systems of NO that account for much of the emission in the ultraviolet region. Research carried out under this project showed that in order to reproduce the observed radiation from the bow shock region of missiles in their boost phase it is necessary to include the Burnett terms in the constituent equation, account for the non-Boltzmann energy distribution, correctly model the NO formation and rotational excitation process, and use accurate transition probabilities for the NO band systems. This work resulted in significant improvements in the computer code NEQAIR that models both the radiation and fluid dynamics in the shock region.

Groundwater nitrate reduction versus dissolved gas production: A tale of two catchments.

PubMed

McAleer, E B; Coxon, C E; Richards, K G; Jahangir, M M R; Grant, J; Mellander, Per E

2017-05-15

At the catchment scale, a complex mosaic of environmental, hydrogeological and physicochemical characteristics combine to regulate the distribution of groundwater and stream nitrate (NO 3 - ). The efficiency of NO 3 - removal (via denitrification) versus the ratio of accumulated reaction products, dinitrogen (excess N 2 ) & nitrous oxide (N 2 O), remains poorly understood. Groundwater was investigated in two well drained agricultural catchments (10km 2 ) in Ireland with contrasting subsurface lithologies (sandstone vs. slate) and landuse. Denitrification capacity was assessed by measuring concentration and distribution patterns of nitrogen (N) species, aquifer hydrogeochemistry, stable isotope signatures and aquifer hydraulic properties. A hierarchy of scale whereby physical factors including agronomy, water table elevation and permeability determined the hydrogeochemical signature of the aquifers was observed. This hydrogeochemical signature acted as the dominant control on denitrification reaction progress. High permeability, aerobic conditions and a lack of bacterial energy sources in the slate catchment resulted in low denitrification reaction progress (0-32%), high NO 3 - and comparatively low N 2 O emission factors (EF 5g 1). In the sandstone catchment denitrification progress ranged from 4 to 94% and was highly dependent on permeability, water table elevation, dissolved oxygen concentration solid phase bacterial energy sources. Denitrification of NO 3 - to N 2 occurred in anaerobic conditions, while at intermediate dissolved oxygen; N 2 O was the dominant reaction product. EF 5g 1 (mean: 0.0018) in the denitrifying sandstone catchment was 32% less than the IPCC default. The denitrification observations across catchments were supported by stable isotope signatures. Stream NO 3 - occurrence was 32% lower in the sandstone catchment even though N loading was substantially higher than the slate catchment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Four-gene Pan-African Blood Signature Predicts Progression to Tuberculosis.

PubMed

Suliman, Sara; Thompson, Ethan; Sutherland, Jayne; Weiner Rd, January; Ota, Martin O C; Shankar, Smitha; Penn-Nicholson, Adam; Thiel, Bonnie; Erasmus, Mzwandile; Maertzdorf, Jeroen; Duffy, Fergal J; Hill, Philip C; Hughes, E Jane; Stanley, Kim; Downing, Katrina; Fisher, Michelle L; Valvo, Joe; Parida, Shreemanta K; van der Spuy, Gian; Tromp, Gerard; Adetifa, Ifedayo M O; Donkor, Simon; Howe, Rawleigh; Mayanja-Kizza, Harriet; Boom, W Henry; Dockrell, Hazel; Ottenhoff, Tom H M; Hatherill, Mark; Aderem, Alan; Hanekom, Willem A; Scriba, Thomas J; Kaufmann, Stefan He; Zak, Daniel E; Walzl, Gerhard

2018-04-06

Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. We investigated biosignatures with predictive ability for incident tuberculosis. In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach. Overall, 79 progressors, who developed tuberculosis between 3 and 24 months following exposure, and 328 matched non-progressors, who remained healthy during 24 months of follow-up, were investigated. A four-transcript signature (RISK4), derived from samples in a South African and Gambian training set, predicted progression up to two years before onset of disease in blinded test set samples from South Africa, The Gambia and Ethiopia with little population-associated variability and also validated on an external cohort of South African adolescents with latent Mycobacterium tuberculosis infection. By contrast, published diagnostic or prognostic tuberculosis signatures predicted on samples from some but not all 3 countries, indicating site-specific variability. Post-hoc meta-analysis identified a single gene pair, C1QC/TRAV27, that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events. Collectively, we developed a simple whole blood-based PCR test to predict tuberculosis in household contacts from diverse African populations, with potential for implementation in national TB contact investigation programs.

Analysis of Forgery Attack on One-Time Proxy Signature and the Improvement

NASA Astrophysics Data System (ADS)

Wang, Tian-Yin; Wei, Zong-Li

2016-02-01

In a recent paper, Yang et al. (Quant. Inf. Process. 13(9), 2007-2016, 2014) analyzed the security of one-time proxy signature scheme Wang and Wei (Quant. Inf. Process. 11(2), 455-463, 2012) and pointed out that it cannot satisfy the security requirements of unforgeability and undeniability because an eavesdropper Eve can forge a valid proxy signature on a message chosen by herself. However, we find that the so-called proxy message-signature pair forged by Eve is issued by the proxy signer in fact, and anybody can obtain it as a requester, which means that the forgery attack is not considered as a successful attack. Therefore, the conclusion that this scheme cannot satisfy the security requirements of proxy signature against forging and denying is not appropriate in this sense. Finally, we study the reason for the misunderstanding and clarify the security requirements for proxy signatures.

Polarization-resolved time-delay signatures of chaos induced by FBG-feedback in VCSEL.

PubMed

Zhong, Zhu-Qiang; Li, Song-Sui; Chan, Sze-Chun; Xia, Guang-Qiong; Wu, Zheng-Mao

2015-06-15

Polarization-resolved chaotic emission intensities from a vertical-cavity surface-emitting laser (VCSEL) subject to feedback from a fiber Bragg grating (FBG) are numerically investigated. Time-delay (TD) signatures of the feedback are examined through various means including self-correlations of intensity time-series of individual polarizations, cross-correlation of intensities time-series between both polarizations, and permutation entropies calculated for the individual polarizations. The results show that the TD signatures can be clearly suppressed by selecting suitable operation parameters such as the feedback strength, FBG bandwidth, and Bragg frequency. Also, in the operational parameter space, numerical maps of TD signatures and effective bandwidths are obtained, which show regions of chaotic signals with both wide bandwidths and weak TD signatures. Finally, by comparing with a VCSEL subject to feedback from a mirror, the VCSEL subject to feedback from the FBG generally shows better concealment of the TD signatures with similar, or even wider, bandwidths.

Ion channel gene expression predicts survival in glioma patients

PubMed Central

Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

2015-01-01

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283

Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

PubMed Central

Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

2016-01-01

Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.

PubMed

Polak, Paz; Kim, Jaegil; Braunstein, Lior Z; Karlic, Rosa; Haradhavala, Nicholas J; Tiao, Grace; Rosebrock, Daniel; Livitz, Dimitri; Kübler, Kirsten; Mouw, Kent W; Kamburov, Atanas; Maruvka, Yosef E; Leshchiner, Ignaty; Lander, Eric S; Golub, Todd R; Zick, Aviad; Orthwein, Alexandre; Lawrence, Michael S; Batra, Rajbir N; Caldas, Carlos; Haber, Daniel A; Laird, Peter W; Shen, Hui; Ellisen, Leif W; D'Andrea, Alan D; Chanock, Stephen J; Foulkes, William D; Getz, Gad

2017-10-01

Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing ∼1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation is strongly associated with signature 3 and, in our data set, was highly enriched in basal-like breast cancers in young individuals of African descent.

Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control▿ †

PubMed Central

Moshkin, Yuri M.; Mohrmann, Lisette; van Ijcken, Wilfred F. J.; Verrijzer, C. Peter

2007-01-01

Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of BAP and PBAP. An RNA interference knockdown survey revealed that the core subunits BRM and MOR are critical for the structural integrity of both complexes. Whole-genome expression profiling suggested that the SWI/SNF core complex is largely dysfunctional in cells. Regulation of the majority of target genes required the signature subunit OSA, PB, or BAP170, suggesting that SWI/SNF remodelers function mostly as holoenzymes. BAP and PBAP execute similar, independent, or antagonistic functions in transcription control and appear to direct mostly distinct biological processes. BAP, but not PBAP, is required for cell cycle progression through mitosis. Because in yeast the PBAP-homologous complex, RSC, controls cell cycle progression, our finding reveals a functional switch during evolution. BAP mediates G2/M transition through direct regulation of string/cdc25. Its signature subunit, OSA, is required for directing BAP to the string/cdc25 promoter. Our results suggest that the core subunits play architectural and enzymatic roles but that the signature subunits determine most of the functional specificity of SWI/SNF holoenzymes in general gene control. PMID:17101803

Security of the arbitrated quantum signature protocols revisited

NASA Astrophysics Data System (ADS)

Kejia, Zhang; Dan, Li; Qi, Su

2014-01-01

Recently, much attention has been paid to the study of arbitrated quantum signature (AQS). Among these studies, the cryptanalysis of some AQS protocols and a series of improved ideas have been proposed. Compared with the previous analysis, we present a security criterion, which can judge whether an AQS protocol is able to prevent the receiver (i.e. one participant in the signature protocol) from forging a legal signature. According to our results, it can be seen that most AQS protocols which are based on the Zeng and Keitel (ZK) model are susceptible to a forgery attack. Furthermore, we present an improved idea of the ZK protocol. Finally, some supplement discussions and several interesting topics are provided.

Feasibility Study of the Development of a Specialized Computer System of Organic Chemical Signatures of Spectral Data.

ERIC Educational Resources Information Center

Scholtz, R. G.; And Others

This final report of a feasibility study describes the research performed in assessing the requirements for a chemical signature file and search scheme for organic compound identification and information retrieval. The research performed to determined feasibility of identifying an unknown compound involved screening the compound against a file of…

Precision diagnostics: moving towards protein biomarker signatures of clinical utility in cancer.

PubMed

Borrebaeck, Carl A K

2017-03-01

Interest in precision diagnostics has been fuelled by the concept that early detection of cancer would benefit patients; that is, if detected early, more tumours should be resectable and treatment more efficacious. Serum contains massive amounts of potentially diagnostic information, and affinity proteomics has risen as an accurate approach to decipher this, to generate actionable information that should result in more precise and evidence-based options to manage cancer. To achieve this, we need to move from single to multiplex biomarkers, a so-called signature, that can provide significantly increased diagnostic accuracy. This Opinion article focuses on the progress being made in identifying protein biomarker signatures of clinical utility, using blood-based proteomics.

Terrain type recognition using ERTS-1 MSS images

NASA Technical Reports Server (NTRS)

Gramenopoulos, N.

1973-01-01

For the automatic recognition of earth resources from ERTS-1 digital tapes, both multispectral and spatial pattern recognition techniques are important. Recognition of terrain types is based on spatial signatures that become evident by processing small portions of an image through selected algorithms. An investigation of spatial signatures that are applicable to ERTS-1 MSS images is described. Artifacts in the spatial signatures seem to be related to the multispectral scanner. A method for suppressing such artifacts is presented. Finally, results of terrain type recognition for one ERTS-1 image are presented.

Mid-wave IR Signatures of CFAV Quest in the North Atlantic Summer and Winter Climates

DTIC Science & Technology

2008-05-01

hiver, ce qui laisse supposer qu’elle pose un plus grand risque de détection du navire. DRDC Atlantic TM 2007-312 i This page intentionally left blank...consacrer ses efforts de gestion des signatures infrarouge. L’objectif final de l’obtention d’un moyen d’optimiser la signature infrarouge des navires...que représentée par le ministre de la Défense nationale, 2008 Original signed by Zahir A. Daya Original signed by Dave Hopkin Original signed by Ron

Black Hole Mergers and Recoils in Low-Mass Galaxies

NASA Astrophysics Data System (ADS)

Blecha, Laura; Kelley, Luke; Koss, Michael; Satyapal, Shobita

2018-01-01

Mergers between massive black holes (BHs) in the intermediate-mass range are one of the most promising sources of gravitational waves (GWs) detectable with LISA. These highly energetic GW events could be observed out to very high redshift, in the epoch where massive BH seeds are thought to form. Despite recent progress, however, much is still not known about the low-mass BH population even in the local Universe. The rates of BH binary formation, inspiral, and merger are also highly uncertain across the BH mass scale. To address these pressing issues in advance of LISA, cosmological hydrodynamics simulations and semi-analytic modeling are being used to model the formation and evolution of BH binaries, and the GW signals they produce. Efforts are also underway to understand the electromagnetic (EM) signatures of the BH binary population. These have proven largely elusive thus far, but an increasing population of BH pairs has been found, and advances in the coming years will provide important comparisons for models of GW sources. Moreover, asymmetry in the GW emission from BH mergers imparts a recoil kick to the merged BH, which in extreme cases can eject the BH from its host galaxy. This creates additional uncertainty in the BH merger rate, but the remnant recoiling BH could be observed as an offset quasar. Identifications of such objects would provide another EM signature of BH mergers that would help pave the way for LISA. We will review model predictions of the BH inspiral and merger rate across the mass scale. We will also describe how the EM signatures of active, merging BHs can be used to constrain theoretical merger rates. Finally, we will discuss the predicted observability of recoiling BHs and ongoing efforts to identify and confirm candidate recoils.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression

PubMed Central

Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R.; Altieri, Dario C.; Vaira, Valentina; Bosari, Silvano

2015-01-01

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the “stemness” marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease. PMID:26107383

Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination

PubMed Central

Corrado, Alessia; Donato, Paolo; Maccari, Silvia; Cecchi, Raffaella; Spadafina, Tiziana; Arcidiacono, Letizia; Tavarini, Simona; Sammicheli, Chiara; Laera, Donatello; Manetti, Andrea Guido Oreste; Ruggiero, Paolo; Galletti, Bruno; Nuti, Sandra; De Gregorio, Ennio; Bertholet, Sylvie; Seubert, Anja; Bagnoli, Fabio; Bensi, Giuliano; Chiarot, Emiliano

2016-01-01

Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans. Characterization of the local and systemic inflammatory and immune responses following bacterial infection brought to light specific signatures of disease. Immunization of mice with the vaccine formulation we have recently described (4C-Staph), induced a strong antibody response and specific CD4+ effector memory T cells, and resulted in reduced bacterial load in the knee joints, a milder general inflammatory state and protection against bacterial-mediated cellular toxicity. Possible correlates of protection are finally proposed, which might contribute to the development of an effective vaccine for human use. PMID:27901071

Inflammatory macrophage-associated 3-gene signature predicts subclinical allograft injury and graft survival.

PubMed

Azad, Tej D; Donato, Michele; Heylen, Line; Liu, Andrew B; Shen-Orr, Shai S; Sweeney, Timothy E; Maltzman, Jonathan Scott; Naesens, Maarten; Khatri, Purvesh

2018-01-25

Late allograft failure is characterized by cumulative subclinical insults manifesting over many years. Although immunomodulatory therapies targeting host T cells have improved short-term survival rates, rates of chronic allograft loss remain high. We hypothesized that other immune cell types may drive subclinical injury, ultimately leading to graft failure. We collected whole-genome transcriptome profiles from 15 independent cohorts composed of 1,697 biopsy samples to assess the association of an inflammatory macrophage polarization-specific gene signature with subclinical injury. We applied penalized regression to a subset of the data sets and identified a 3-gene inflammatory macrophage-derived signature. We validated discriminatory power of the 3-gene signature in 3 independent renal transplant data sets with mean AUC of 0.91. In a longitudinal cohort, the 3-gene signature strongly correlated with extent of injury and accurately predicted progression of subclinical injury 18 months before clinical manifestation. The 3-gene signature also stratified patients at high risk of graft failure as soon as 15 days after biopsy. We found that the 3-gene signature also distinguished acute rejection (AR) accurately in 3 heart transplant data sets but not in lung transplant. Overall, we identified a parsimonious signature capable of diagnosing AR, recognizing subclinical injury, and risk-stratifying renal transplant patients. Our results strongly suggest that inflammatory macrophages may be a viable therapeutic target to improve long-term outcomes for organ transplantation patients.

Gene Expression Signatures Based on Variability can Robustly Predict Tumor Progression and Prognosis

PubMed Central

Dinalankara, Wikum; Bravo, Héctor Corrada

2015-01-01

Gene expression signatures are commonly used to create cancer prognosis and diagnosis methods, yet only a small number of them are successfully deployed in the clinic since many fail to replicate performance on subsequent validation. A primary reason for this lack of reproducibility is the fact that these signatures attempt to model the highly variable and unstable genomic behavior of cancer. Our group recently introduced gene expression anti-profiles as a robust methodology to derive gene expression signatures based on the observation that while gene expression measurements are highly heterogeneous across tumors of a specific cancer type relative to the normal tissue, their degree of deviation from normal tissue expression in specific genes involved in tissue differentiation is a stable tumor mark that is reproducible across experiments and cancer types. Here we show that constructing gene expression signatures based on variability and the anti-profile approach yields classifiers capable of successfully distinguishing benign growths from cancerous growths based on deviation from normal expression. We then show that this same approach generates stable and reproducible signatures that predict probability of relapse and survival based on tumor gene expression. These results suggest that using the anti-profile framework for the discovery of genomic signatures is an avenue leading to the development of reproducible signatures suitable for adoption in clinical settings. PMID:26078586

Gene-expression signatures can distinguish gastric cancer grades and stages.

PubMed

Cui, Juan; Li, Fan; Wang, Guoqing; Fang, Xuedong; Puett, J David; Xu, Ying

2011-03-18

Microarray gene-expression data of 54 paired gastric cancer and adjacent noncancerous gastric tissues were analyzed, with the aim to establish gene signatures for cancer grades (well-, moderately-, poorly- or un-differentiated) and stages (I, II, III and IV), which have been determined by pathologists. Our statistical analysis led to the identification of a number of gene combinations whose expression patterns serve well as signatures of different grades and different stages of gastric cancer. A 19-gene signature was found to have discerning power between high- and low-grade gastric cancers in general, with overall classification accuracy at 79.6%. An expanded 198-gene panel allows the stratification of cancers into four grades and control, giving rise to an overall classification agreement of 74.2% between each grade designated by the pathologists and our prediction. Two signatures for cancer staging, consisting of 10 genes and 9 genes, respectively, provide high classification accuracies at 90.0% and 84.0%, among early-, advanced-stage cancer and control. Functional and pathway analyses on these signature genes reveal the significant relevance of the derived signatures to cancer grades and progression. To the best of our knowledge, this represents the first study on identification of genes whose expression patterns can serve as markers for cancer grades and stages.

Label-Free Molecular Imaging of Biological Cells and Tissues by Linear and Nonlinear Raman Spectroscopic Approaches.

PubMed

Krafft, Christoph; Schmitt, Michael; Schie, Iwan W; Cialla-May, Dana; Matthäus, Christian; Bocklitz, Thomas; Popp, Jürgen

2017-04-10

Raman spectroscopy is an emerging technique in bioanalysis and imaging of biomaterials owing to its unique capability of generating spectroscopic fingerprints. Imaging cells and tissues by Raman microspectroscopy represents a nondestructive and label-free approach. All components of cells or tissues contribute to the Raman signals, giving rise to complex spectral signatures. Resonance Raman scattering and surface-enhanced Raman scattering can be used to enhance the signals and reduce the spectral complexity. Raman-active labels can be introduced to increase specificity and multimodality. In addition, nonlinear coherent Raman scattering methods offer higher sensitivities, which enable the rapid imaging of larger sampling areas. Finally, fiber-based imaging techniques pave the way towards in vivo applications of Raman spectroscopy. This Review summarizes the basic principles behind medical Raman imaging and its progress since 2012. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vibration Signature Analysis of a Faulted Gear Transmission System

NASA Technical Reports Server (NTRS)

Choy, F. K.; Huang, S.; Zakrajsek, J. J.; Handschuh, R. F.; Townsend, D. P.

1994-01-01

A comprehensive procedure in predicting faults in gear transmission systems under normal operating conditions is presented. Experimental data was obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. Time synchronous averaged vibration data was recorded throughout the test as the fault progressed from a small single pit to severe pitting over several teeth, and finally tooth fracture. A numerical procedure based on the Winger-Ville distribution was used to examine the time averaged vibration data. Results from the Wigner-Ville procedure are compared to results from a variety of signal analysis techniques which include time domain analysis methods and frequency analysis methods. Using photographs of the gear tooth at various stages of damage, the limitations and accuracy of the various techniques are compared and discussed. Conclusions are drawn from the comparison of the different approaches as well as the applicability of the Wigner-Ville method in predicting gear faults.

Nest signature changes throughout colony cycle and after social parasite invasion in social wasps

PubMed Central

Blancato, Giuliano; Picchi, Laura; Lucas, Christophe

2017-01-01

Social insects recognize their nestmates by means of a cuticular hydrocarbon signature shared by colony members, but how nest signature changes across time has been rarely tested in longitudinal studies and in the field. In social wasps, the chemical signature is also deposited on the nest surface, where it is used by newly emerged wasps as a reference to learn their colony odor. Here, we investigate the temporal variations of the chemical signature that wasps have deposited on their nests. We followed the fate of the colonies of the social paper wasp Polistes biglumis in their natural environment from colony foundation to decline. Because some colonies were invaded by the social parasite Polistes atrimandibularis, we also tested the effects of social parasites on the nest signature. We observed that, as the season progresses, the nest signature changed; the overall abundance of hydrocarbons as well as the proportion of longer-chain and branched hydrocarbons increased. Where present, social parasites altered the host-nest signature qualitatively (adding parasite-specific alkenes) and quantitatively (by interfering with the increase in overall hydrocarbon abundance). Our results show that 1) colony odor is highly dynamic both in colonies controlled by legitimate foundresses and in those controlled by social parasites; 2) emerged offspring contribute little to colony signature, if at all, in comparison to foundresses; and 3) social parasites, that later mimic host signature, initially mark host nests with species-specific hydrocarbons. This study implies that important updating of the neural template used in nestmate recognition should occur in social insects. PMID:29261775

Viking lander camera geometry calibration report. Volume 1: Test methods and data reduction techniques

NASA Technical Reports Server (NTRS)

Wolf, M. B.

1981-01-01

The determination and removal of instrument signature from Viking Lander camera geometric data are described. All tests conducted as well as a listing of the final database (calibration constants) used to remove instrument signature from Viking Lander flight images are included. The theory of the geometric aberrations inherent in the Viking Lander camera is explored.

Infrared signature modelling of a rocket jet plume - comparison with flight measurements

NASA Astrophysics Data System (ADS)

Rialland, V.; Guy, A.; Gueyffier, D.; Perez, P.; Roblin, A.; Smithson, T.

2016-01-01

The infrared signature modelling of rocket plumes is a challenging problem involving rocket geometry, propellant composition, combustion modelling, trajectory calculations, fluid mechanics, atmosphere modelling, calculation of gas and particles radiative properties and of radiative transfer through the atmosphere. This paper presents ONERA simulation tools chained together to achieve infrared signature prediction, and the comparison of the estimated and measured signatures of an in-flight rocket plume. We consider the case of a solid rocket motor with aluminized propellant, the Black Brant sounding rocket. The calculation case reproduces the conditions of an experimental rocket launch, performed at White Sands in 1997, for which we obtained high quality infrared signature data sets from DRDC Valcartier. The jet plume is calculated using an in-house CFD software called CEDRE. The plume infrared signature is then computed on the spectral interval 1900-5000 cm-1 with a step of 5 cm-1. The models and their hypotheses are presented and discussed. Then the resulting plume properties, radiance and spectra are detailed. Finally, the estimated infrared signature is compared with the spectral imaging measurements. The discrepancies are analyzed and discussed.

Using stamping punch force variation for the identification of changes in lubrication and wear mechanism

NASA Astrophysics Data System (ADS)

Voss, B. M.; Pereira, M. P.; Rolfe, B. F.; Doolan, M. C.

2017-09-01

The growth in use of Advanced High Strength Steels in the automotive industry for light-weighting and safety has increased the rates of tool wear in sheet metal stamping. This is an issue that adds significant costs to production in terms of manual inspection and part refinishing. To reduce these costs, a tool condition monitoring system is required and a firm understanding of process signal variation must form the foundation for any such monitoring system. Punch force is a stamping process signal that is widely collected by industrial presses and has been linked closely to part quality and tool condition, making it an ideal candidate as a tool condition monitoring signal. In this preliminary investigation, the variation of punch force due to different lubrication conditions and progressive wear are examined. Linking specific punch force signature changes to developing lubrication and wear events is valuable for die wear and stamping condition monitoring. A series of semi-industrial channel forming trials were conducted under different lubrication regimes and progressive die wear. Punch force signatures were captured for each part and Principal Component Analysis (PCA) was applied to determine the key Principal Components of the signature data sets. These Principal Components were linked to the evolution of friction conditions over the course of the stroke for the different lubrication regimes and mechanism of galling wear. As a result, variation in punch force signatures were correlated to the current mechanism of wear dominant on the formed part; either abrasion or adhesion, and to changes in lubrication mechanism. The outcomes of this study provide important insights into punch force signature variation, that will provide a foundation for future work into the development of die wear and lubrication monitoring systems for sheet metal stamping.

Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

PubMed

Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

2015-12-15

Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

EG-07CELL CYCLE SIGNATURE AND TUMOR PHYLOGENY ARE ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION IN GLIOMA

PubMed Central

Mazor, Tali; Pankov, Aleksandr; Johnson, Brett E.; Hong, Chibo; Bell, Robert J.A.; Smirnov, Ivan V.; Reis, Gerald F.; Phillips, Joanna J.; Barnes, Michael; Bollen, Andrew W.; Taylor, Barry S.; Molinaro, Annette M.; Olshen, Adam B.; Song, Jun S.; Berger, Mitchel S.; Chang, Susan M.; Costello, Joseph F.

2014-01-01

The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states, including DNA methylation, are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover tumor phylogeny. Here we examined the spatial and temporal dynamics of DNA methylation in a clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. WHO grade II gliomas are diffuse, infiltrative tumors that frequently recur and may undergo malignant progression to a higher grade with a worse prognosis. The extent to which epigenetic alterations contribute to the evolution of low-grade gliomas, including malignant progression, is unknown. While all gliomas in the cohort exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent malignant progression to high-grade glioblastoma (GBM) had a unique signature of DNA hypomethylation enriched for active enhancers, as well as sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic trees robustly recapitulated phylogenetic trees derived from somatic mutations in the same patients. These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent glioma.

Network information improves cancer outcome prediction.

PubMed

Roy, Janine; Winter, Christof; Isik, Zerrin; Schroeder, Michael

2014-07-01

Disease progression in cancer can vary substantially between patients. Yet, patients often receive the same treatment. Recently, there has been much work on predicting disease progression and patient outcome variables from gene expression in order to personalize treatment options. Despite first diagnostic kits in the market, there are open problems such as the choice of random gene signatures or noisy expression data. One approach to deal with these two problems employs protein-protein interaction networks and ranks genes using the random surfer model of Google's PageRank algorithm. In this work, we created a benchmark dataset collection comprising 25 cancer outcome prediction datasets from literature and systematically evaluated the use of networks and a PageRank derivative, NetRank, for signature identification. We show that the NetRank performs significantly better than classical methods such as fold change or t-test. Despite an order of magnitude difference in network size, a regulatory and protein-protein interaction network perform equally well. Experimental evaluation on cancer outcome prediction in all of the 25 underlying datasets suggests that the network-based methodology identifies highly overlapping signatures over all cancer types, in contrast to classical methods that fail to identify highly common gene sets across the same cancer types. Integration of network information into gene expression analysis allows the identification of more reliable and accurate biomarkers and provides a deeper understanding of processes occurring in cancer development and progression. © The Author 2012. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Injuries to law enforcement officers: the backface signature injury.

PubMed

Wilhelm, Marianne; Bir, Cynthia

2008-01-15

In today's law enforcement community, one of the most vital tools an officer can possess is personal body armor. However, a recent Department of Justice investigation has raised important questions regarding the protection actually afforded officers through the use of personal body armor, and the current test methods used to assess the armor. Test results show that most Zylon-containing vests showed deformations in excess of the 0101.04 Standard's 44 mm backface signature limit. Such increased deformation can lead to serious injuries, including backface signature injuries, which have occurred in the field. Although the vest is successful in containing the round, it is not effectively dissipating the energy enough to prevent large amounts of vest deformation at the area of impact. Therefore, open, penetrating wounds occur even though the bullet did not penetrate the vest. The objective of the current study was to further define the backface signature injury through the use of case studies and laboratory experiments. Following the case study investigation, backface signature testing was conducted using a clay medium based on the NIJ 0101.04 Standard. The final component of this research involved the use of post-mortem human specimens (PMHS) for further investigation of the backface signature injury. Although the underlying cause of backface signature injuries is unknown, energy density is likely to play a role in the mechanism. Energy density (E/a) is defined as the energy per unit area and has been previously used in less lethal skin penetration research. Further research into the underlying causes of backface signature injuries is necessary. In addition to armor testing, the study of law enforcement personnel who have been shot while wearing soft body armor is also a valuable tool for determining the effectiveness of certification standards. Finally, it is important for medical personnel to recognize the backface signature injury and document this as a type of injury separate from blunt trauma or penetrating trauma behind armor injuries. Detailed knowledge of the injury, including the depth of the wound, would be beneficial to the scientific community.

miRNA signature associated with outcome of gastric cancer patients following chemotherapy

PubMed Central

2011-01-01

Background Identification of patients who likely will or will not benefit from cytotoxic chemotherapy through the use of biomarkers could greatly improve clinical management by better defining appropriate treatment options for patients. microRNAs may be potentially useful biomarkers that help guide individualized therapy for cancer because microRNA expression is dysregulated in cancer. In order to identify miRNA signatures for gastric cancer and for predicting clinical resistance to cisplatin/fluorouracil (CF) chemotherapy, a comprehensive miRNA microarray analysis was performed using endoscopic biopsy samples. Methods Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify a miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) of disease after CF therapy. Results A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with TTP whereas 28 miRNAs were significantly positively correlated with TTP of 82 cancer patients (P<0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose. Conclusions We have identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with TTP after CF therapy. The chemoresistance miRNA expression signature includes several miRNAs previously shown to regulate apoptosis in vitro, and warrants further validation. PMID:22112324

Gene signature based on degradome-related genes can predict distal metastasis in cervical cancer patients.

PubMed

Fernandez-Retana, Jorge; Zamudio-Meza, Horacio; Rodriguez-Morales, Miguel; Pedroza-Torres, Abraham; Isla-Ortiz, David; Herrera, Luis; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; López-Camarillo, César; Morales-Gonzalez, Fermin; Cantu de Leon, David; Pérez-Plasencia, Carlos

2017-06-01

Cervical cancer is one of the leading causes of death in women worldwide, which mainly affects developing countries. The patients who suffer a recurrence and/or progression disease have a higher risk of developing distal metastases. Proteases comprising the degradome given its ability to promote cell growth, migration, and invasion of tissues play an important role during tumor development and progression. In this study, we used high-density microarrays and quantitative reverse transcriptase polymerase chain reaction to evaluate the degradome profile and their inhibitors in 112 samples of patients diagnosed with locally advanced cervical cancer. Clinical follow-up was done during a period of 3 years. Using a correlation analysis between the response to treatment and the development of metastasis, we established a molecular signature comprising eight degradome-related genes (FAM111B, FAM111A, CFB, PSMB8, PSMB9, CASP7, PRSS16, and CD74) with the ability to discriminate patients at risk of distal metastases. In conclusion, present results show that molecular signature obtained from degradome genes can predict the possibility of metastasis in patients with locally advanced cervical cancer.

Observation of Discrete-Time-Crystal Signatures in an Ordered Dipolar Many-Body System

NASA Astrophysics Data System (ADS)

Rovny, Jared; Blum, Robert L.; Barrett, Sean E.

2018-05-01

A discrete time crystal (DTC) is a robust phase of driven systems that breaks the discrete time translation symmetry of the driving Hamiltonian. Recent experiments have observed DTC signatures in two distinct systems. Here we show nuclear magnetic resonance observations of DTC signatures in a third, strikingly different system: an ordered spatial crystal. We use a novel DTC echo experiment to probe the coherence of the driven system. Finally, we show that interactions during the pulse of the DTC sequence contribute to the decay of the signal, complicating attempts to measure the intrinsic lifetime of the DTC.

Observation of Discrete-Time-Crystal Signatures in an Ordered Dipolar Many-Body System.

PubMed

Rovny, Jared; Blum, Robert L; Barrett, Sean E

2018-05-04

A discrete time crystal (DTC) is a robust phase of driven systems that breaks the discrete time translation symmetry of the driving Hamiltonian. Recent experiments have observed DTC signatures in two distinct systems. Here we show nuclear magnetic resonance observations of DTC signatures in a third, strikingly different system: an ordered spatial crystal. We use a novel DTC echo experiment to probe the coherence of the driven system. Finally, we show that interactions during the pulse of the DTC sequence contribute to the decay of the signal, complicating attempts to measure the intrinsic lifetime of the DTC.

Cryptanalysis of the Quantum Group Signature Protocols

NASA Astrophysics Data System (ADS)

Zhang, Ke-Jia; Sun, Ying; Song, Ting-Ting; Zuo, Hui-Juan

2013-11-01

Recently, the researches of quantum group signature (QGS) have attracted a lot of attentions and some typical protocols have been designed for e-payment system, e-government, e-business, etc. In this paper, we analyze the security of the quantum group signature with the example of two novel protocols. It can be seen that both of them cannot be implemented securely since the arbitrator cannot solve the disputes fairly. In order to show that, some possible attack strategies, which can be used by the malicious participants, are proposed. Moreover, the further discussions of QGS are presented finally, including some insecurity factors and improved ideas.

Distinct Microbial Signatures Associated With Different Breast Cancer Types

PubMed Central

Banerjee, Sagarika; Tian, Tian; Wei, Zhi; Shih, Natalie; Feldman, Michael D.; Peck, Kristen N.; DeMichele, Angela M.; Alwine, James C.; Robertson, Erle S.

2018-01-01

A dysbiotic microbiome can potentially contribute to the pathogenesis of many different diseases including cancer. Breast cancer is the second leading cause of cancer death in women. Thus, we investigated the diversity of the microbiome in the four major types of breast cancer: endocrine receptor (ER) positive, triple positive, Her2 positive and triple negative breast cancers. Using a whole genome and transcriptome amplification and a pan-pathogen microarray (PathoChip) strategy, we detected unique and common viral, bacterial, fungal and parasitic signatures for each of the breast cancer types. These were validated by PCR and Sanger sequencing. Hierarchical cluster analysis of the breast cancer samples, based on their detected microbial signatures, showed distinct patterns for the triple negative and triple positive samples, while the ER positive and Her2 positive samples shared similar microbial signatures. These signatures, unique or common to the different breast cancer types, provide a new line of investigation to gain further insights into prognosis, treatment strategies and clinical outcome, as well as better understanding of the role of the micro-organisms in the development and progression of breast cancer. PMID:29867857

High order statistical signatures from source-driven measurements of subcritical fissile systems

NASA Astrophysics Data System (ADS)

Mattingly, John Kelly

1998-11-01

This research focuses on the development and application of high order statistical analyses applied to measurements performed with subcritical fissile systems driven by an introduced neutron source. The signatures presented are derived from counting statistics of the introduced source and radiation detectors that observe the response of the fissile system. It is demonstrated that successively higher order counting statistics possess progressively higher sensitivity to reactivity. Consequently, these signatures are more sensitive to changes in the composition, fissile mass, and configuration of the fissile assembly. Furthermore, it is shown that these techniques are capable of distinguishing the response of the fissile system to the introduced source from its response to any internal or inherent sources. This ability combined with the enhanced sensitivity of higher order signatures indicates that these techniques will be of significant utility in a variety of applications. Potential applications include enhanced radiation signature identification of weapons components for nuclear disarmament and safeguards applications and augmented nondestructive analysis of spent nuclear fuel. In general, these techniques expand present capabilities in the analysis of subcritical measurements.

AdaBoost-based on-line signature verifier

NASA Astrophysics Data System (ADS)

Hongo, Yasunori; Muramatsu, Daigo; Matsumoto, Takashi

2005-03-01

Authentication of individuals is rapidly becoming an important issue. The authors previously proposed a Pen-input online signature verification algorithm. The algorithm considers a writer"s signature as a trajectory of pen position, pen pressure, pen azimuth, and pen altitude that evolve over time, so that it is dynamic and biometric. Many algorithms have been proposed and reported to achieve accuracy for on-line signature verification, but setting the threshold value for these algorithms is a problem. In this paper, we introduce a user-generic model generated by AdaBoost, which resolves this problem. When user- specific models (one model for each user) are used for signature verification problems, we need to generate the models using only genuine signatures. Forged signatures are not available because imposters do not give forged signatures for training in advance. However, we can make use of another's forged signature in addition to the genuine signatures for learning by introducing a user generic model. And Adaboost is a well-known classification algorithm, making final decisions depending on the sign of the output value. Therefore, it is not necessary to set the threshold value. A preliminary experiment is performed on a database consisting of data from 50 individuals. This set consists of western-alphabet-based signatures provide by a European research group. In this experiment, our algorithm gives an FRR of 1.88% and an FAR of 1.60%. Since no fine-tuning was done, this preliminary result looks very promising.

Proceedings of the Ground Target Modeling and Validation Conference (13th) Held in Houghton, MI on 5-8 August 2002

DTIC Science & Technology

2002-08-01

excessively high aspect ratio, the forward region of the original model was removed. The final grid (rear half) had 383104 computational cells compared...45 Session III: Thermal Signature Modeling and Validation Session...Chair: Dr. Dieter Clement, FGAN-FOM " Modeling the Thermal Signature of Natural Backgrounds" Marius Gamborg, Norwegian Defence Research Establishm

matK-QR classifier: a patterns based approach for plant species identification.

PubMed

More, Ravi Prabhakar; Mane, Rupali Chandrashekhar; Purohit, Hemant J

2016-01-01

DNA barcoding is widely used and most efficient approach that facilitates rapid and accurate identification of plant species based on the short standardized segment of the genome. The nucleotide sequences of maturaseK ( matK ) and ribulose-1, 5-bisphosphate carboxylase ( rbcL ) marker loci are commonly used in plant species identification. Here, we present a new and highly efficient approach for identifying a unique set of discriminating nucleotide patterns to generate a signature (i.e. regular expression) for plant species identification. In order to generate molecular signatures, we used matK and rbcL loci datasets, which encompass 125 plant species in 52 genera reported by the CBOL plant working group. Initially, we performed Multiple Sequence Alignment (MSA) of all species followed by Position Specific Scoring Matrix (PSSM) for both loci to achieve a percentage of discrimination among species. Further, we detected Discriminating Patterns (DP) at genus and species level using PSSM for the matK dataset. Combining DP and consecutive pattern distances, we generated molecular signatures for each species. Finally, we performed a comparative assessment of these signatures with the existing methods including BLASTn, Support Vector Machines (SVM), Jrip-RIPPER, J48 (C4.5 algorithm), and the Naïve Bayes (NB) methods against NCBI-GenBank matK dataset. Due to the higher discrimination success obtained with the matK as compared to the rbcL , we selected matK gene for signature generation. We generated signatures for 60 species based on identified discriminating patterns at genus and species level. Our comparative assessment results suggest that a total of 46 out of 60 species could be correctly identified using generated signatures, followed by BLASTn (34 species), SVM (18 species), C4.5 (7 species), NB (4 species) and RIPPER (3 species) methods As a final outcome of this study, we converted signatures into QR codes and developed a software matK -QR Classifier (http://www.neeri.res.in/matk_classifier/index.htm), which search signatures in the query matK gene sequences and predict corresponding plant species. This novel approach of employing pattern-based signatures opens new avenues for the classification of species. In addition to existing methods, we believe that matK -QR Classifier would be a valuable tool for molecular taxonomists enabling precise identification of plant species.

Molecular Phenotypes Distinguish Patients with Relatively Stable from Progressive Idiopathic Pulmonary Fibrosis (IPF)

PubMed Central

Boon, Kathy; Bailey, Nathaniel W.; Yang, Jun; Steel, Mark P.; Groshong, Steve; Kervitsky, Dolly; Brown, Kevin K.; Schwarz, Marvin I.; Schwartz, David A.

2009-01-01

Background Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic interstitial lung disease that is unresponsive to current therapy and often leads to death. However, the rate of disease progression differs among patients. We hypothesized that comparing the gene expression profiles between patients with stable disease and those in which the disease progressed rapidly will lead to biomarker discovery and contribute to the understanding of disease pathogenesis. Methodology and Principal Findings To begin to address this hypothesis, we applied Serial Analysis of Gene Expression (SAGE) to generate lung expression profiles from diagnostic surgical lung biopsies in 6 individuals with relatively stable (or slowly progressive) IPF and 6 individuals with progressive IPF (based on changes in DLCO and FVC over 12 months). Our results indicate that this comprehensive lung IPF SAGE transcriptome is distinct from normal lung tissue and other chronic lung diseases. To identify candidate markers of disease progression, we compared the IPF SAGE profiles in stable and progressive disease, and identified a set of 102 transcripts that were at least 5-fold up regulated and a set of 89 transcripts that were at least 5-fold down regulated in the progressive group (P-value≤0.05). The over expressed genes included surfactant protein A1, two members of the MAPK-EGR-1-HSP70 pathway that regulate cigarette-smoke induced inflammation, and Plunc (palate, lung and nasal epithelium associated), a gene not previously implicated in IPF. Interestingly, 26 of the up regulated genes are also increased in lung adenocarcinomas and have low or no expression in normal lung tissue. More importantly, we defined a SAGE molecular expression signature of 134 transcripts that sufficiently distinguished relatively stable from progressive IPF. Conclusions These findings indicate that molecular signatures from lung parenchyma at the time of diagnosis could prove helpful in predicting the likelihood of disease progression or possibly understanding the biological activity of IPF. PMID:19347046

A Framework for Network Visualisation: Progress Report

DTIC Science & Technology

2006-12-01

time; secondly a simple oscillation, in which traffic changes, but those changes repeat periodically; or thirdly, a “ strange attractor ”, a pattern of...changes that never repeats exactly, though it may appear to repeat approximately. The strange attractor is the signature of a chaotic system, which...IST-063 3 - 1 Taylor, M.M. (2006) A Framework for Network Visualisation: Progress Report. In Visualising Network Information (pp. 3-1 – 3-22

Identification of gene expression signature for cigarette smoke exposure response--from man to mouse.

PubMed

Martin, F; Talikka, M; Hoeng, J; Peitsch, M C

2015-12-01

Gene expression profiling data can be used in toxicology to assess both the level and impact of toxicant exposure, aligned with a vision of 21st century toxicology. Here, we present a whole blood-derived gene signature that can distinguish current smokers from either nonsmokers or former smokers with high specificity and sensitivity. Such a signature that can be measured in a surrogate tissue (whole blood) may help in monitoring smoking exposure as well as discontinuation of exposure when the primarily impacted tissue (e.g., lung) is not readily accessible. The signature consisted of LRRN3, SASH1, PALLD, RGL1, TNFRSF17, CDKN1C, IGJ, RRM2, ID3, SERPING1, and FUCA1. Several members of this signature have been previously described in the context of smoking. The signature translated well across species and could distinguish mice that were exposed to cigarette smoke from ones exposed to air only or had been withdrawn from cigarette smoke exposure. Finally, the small signature of only 11 genes could be converted into a polymerase chain reaction-based assay that could serve as a marker to monitor compliance with a smoking abstinence protocol. © The Author(s) 2015.

Secure Obfuscation for Encrypted Group Signatures

PubMed Central

Fan, Hongfei; Liu, Qin

2015-01-01

In recent years, group signature techniques are widely used in constructing privacy-preserving security schemes for various information systems. However, conventional techniques keep the schemes secure only in normal black-box attack contexts. In other words, these schemes suppose that (the implementation of) the group signature generation algorithm is running in a platform that is perfectly protected from various intrusions and attacks. As a complementary to existing studies, how to generate group signatures securely in a more austere security context, such as a white-box attack context, is studied in this paper. We use obfuscation as an approach to acquire a higher level of security. Concretely, we introduce a special group signature functionality-an encrypted group signature, and then provide an obfuscator for the proposed functionality. A series of new security notions for both the functionality and its obfuscator has been introduced. The most important one is the average-case secure virtual black-box property w.r.t. dependent oracles and restricted dependent oracles which captures the requirement of protecting the output of the proposed obfuscator against collision attacks from group members. The security notions fit for many other specialized obfuscators, such as obfuscators for identity-based signatures, threshold signatures and key-insulated signatures. Finally, the correctness and security of the proposed obfuscator have been proven. Thereby, the obfuscated encrypted group signature functionality can be applied to variants of privacy-preserving security schemes and enhance the security level of these schemes. PMID:26167686

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival.

PubMed

Botta, C; Di Martino, M T; Ciliberto, D; Cucè, M; Correale, P; Rossi, M; Tagliaferri, P; Tassone, P

2016-12-16

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.

PubMed

Irizar, Haritz; Goñi, Joaquín; Alzualde, Ainhoa; Castillo-Triviño, Tamara; Olascoaga, Javier; Lopez de Munain, Adolfo; Otaegui, David

2015-12-01

Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non-Small-Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab.

PubMed

Higgs, Brandon W; Morehouse, Christopher; Streicher, Katie L; Brohawn, Philip; Pilataxi, Fernanda; Gupta, Ashok; Ranade, Koustubh

2018-05-01

To identify a predictive biomarker for durvalumab, an anti-programmed death ligand 1 (PD-L1) monoclonal antibody. RNA sequencing of 97 advanced-stage non-small-cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase 1b/2 clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer (UC) tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and UC with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1+). Kaplan-Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA).  In the NSCLC discovery set, a four-gene interferon gamma (IFNγ)-positive (IFNγ+) signature comprising IFNγ, CD274, LAG3, and CXCL9 was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ+-signature NSCLC patients had improved survival regardless of immunohistochemistry (IHC) PD-L1 status. These associations were replicated in a UC cohort. The IFNγ+ signature was induced twofold (P = 0.003) by durvalumab after 8 weeks of therapy in NSCLC patients, and baseline signature was associated with TMB but not survival in TCGA data.  The IFNγ+ mRNA signature may assist in identifying patients with improved outcomes to durvalumab, independent of PD-L1 assessed by IHC. Copyright ©2018, American Association for Cancer Research.

Fourier transform infra-red spectroscopic signatures for lung cells' epithelial mesenchymal transition: A preliminary report

NASA Astrophysics Data System (ADS)

Sarkar, Atasi; Sengupta, Sanghamitra; Mukherjee, Anirban; Chatterjee, Jyotirmoy

2017-02-01

Infra red (IR) spectral characterization can provide label-free cellular metabolic signatures of normal and diseased circumstances in a rapid and non-invasive manner. Present study endeavoured to enlist Fourier transform infra red (FTIR) spectroscopic signatures for lung normal and cancer cells during chemically induced epithelial mesenchymal transition (EMT) for which global metabolic dimension is not well reported yet. Occurrence of EMT was validated with morphological and immunocytochemical confirmation. Pre-processed spectral data was analyzed using ANOVA and principal component analysis-linear discriminant analysis (PCA-LDA). Significant differences observed in peak area corresponding to biochemical fingerprint (900-1800 cm- 1) and high wave-number (2800-3800 cm- 1) regions contributed to adequate PCA-LDA segregation of cells undergoing EMT. The findings were validated by re-analysis of data using another in-house built binary classifier namely vector valued regularized kernel approximation (VVRKFA), in order to understand EMT progression. To improve the classification accuracy, forward feature selection (FFS) tool was employed in extracting potent spectral signatures by eliminating undesirable noise. Gradual increase in classification accuracy with EMT progression of both cell types indicated prominence of the biochemical alterations. Rapid changes in cellular metabolome noted in cancer cells within first 24 h of EMT induction along with higher classification accuracy for cancer cell groups in comparison to normal cells might be attributed to inherent differences between them. Spectral features were suggestive of EMT triggered changes in nucleic acid, protein, lipid and bound water contents which can emerge as the useful markers to capture EMT related cellular characteristics.

In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

PubMed Central

Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-01

Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.

PubMed

Pescatori, Mario; Broccolini, Aldobrando; Minetti, Carlo; Bertini, Enrico; Bruno, Claudio; D'amico, Adele; Bernardini, Camilla; Mirabella, Massimiliano; Silvestri, Gabriella; Giglio, Vincenzo; Modoni, Anna; Pedemonte, Marina; Tasca, Giorgio; Galluzzi, Giuliana; Mercuri, Eugenio; Tonali, Pietro A; Ricci, Enzo

2007-04-01

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

Common disease signatures from gene expression analysis in Huntington's disease human blood and brain.

PubMed

Mina, Eleni; van Roon-Mom, Willeke; Hettne, Kristina; van Zwet, Erik; Goeman, Jelle; Neri, Christian; A C 't Hoen, Peter; Mons, Barend; Roos, Marco

2016-08-01

Huntington's disease (HD) is a devastating brain disorder with no effective treatment or cure available. The scarcity of brain tissue makes it hard to study changes in the brain and impossible to perform longitudinal studies. However, peripheral pathology in HD suggests that it is possible to study the disease using peripheral tissue as a monitoring tool for disease progression and/or efficacy of novel therapies. In this study, we investigated if blood can be used to monitor disease severity and progression in brain. Since previous attempts using only gene expression proved unsuccessful, we compared blood and brain Huntington's disease signatures in a functional context. Microarray HD gene expression profiles from three brain regions were compared to the transcriptome of HD blood generated by next generation sequencing. The comparison was performed with a combination of weighted gene co-expression network analysis and literature based functional analysis (Concept Profile Analysis). Uniquely, our comparison of blood and brain datasets was not based on (the very limited) gene overlap but on the similarity between the gene annotations in four different semantic categories: "biological process", "cellular component", "molecular function" and "disease or syndrome". We identified signatures in HD blood reflecting a broad pathophysiological spectrum, including alterations in the immune response, sphingolipid biosynthetic processes, lipid transport, cell signaling, protein modification, spliceosome, RNA splicing, vesicle transport, cell signaling and synaptic transmission. Part of this spectrum was reminiscent of the brain pathology. The HD signatures in caudate nucleus and BA4 exhibited the highest similarity with blood, irrespective of the category of semantic annotations used. BA9 exhibited an intermediate similarity, while cerebellum had the least similarity. We present two signatures that were shared between blood and brain: immune response and spinocerebellar ataxias. Our results demonstrate that HD blood exhibits dysregulation that is similar to brain at a functional level, but not necessarily at the level of individual genes. We report two common signatures that can be used to monitor the pathology in brain of HD patients in a non-invasive manner. Our results are an exemplar of how signals in blood data can be used to represent brain disorders. Our methodology can be used to study disease specific signatures in diseases where heterogeneous tissues are involved in the pathology.

Observational signatures of self-destructive civilizations

NASA Astrophysics Data System (ADS)

Stevens, Adam; Forgan, Duncan; James, Jack O'malley

2016-10-01

We address the possibility that intelligent civilizations that destroy themselves could present signatures observable by humanity. Placing limits on the number of self-destroyed civilizations in the Milky Way has strong implications for the final three terms in Drake's Equation, and would allow us to identify which classes of solution to Fermi's Paradox fit with the evidence (or lack thereof). Using the Earth as an example, we consider a variety of scenarios in which humans could extinguish their own technological civilization. Each scenario presents some form of observable signature that could be probed by astronomical campaigns to detect and characterize extrasolar planetary systems. Some observables are unlikely to be detected at interstellar distances, but some scenarios are likely to produce significant changes in atmospheric composition that could be detected serendipitously with next-generation telescopes. In some cases, the timing of the observation would prove crucial to detection, as the decay of signatures is rapid compared with humanity's communication lifetime. In others, the signatures persist on far longer timescales.

Preliminary sonic boom correlation of predicted and measured levels for STS-1 entry

NASA Technical Reports Server (NTRS)

Garcia, F., Jr.; Morrison, K. M.; Jones, J. H.; Henderson, H. R.

1982-01-01

A preliminary analysis correlating peaks from sonic boom pressure signatures recorded during the descent trajectory of the Orbiter Columbia, which landed in the dry lake bed at Edwards Air Force Base (EAFB), California, with measured wind tunnel signatures extrapolated from flight altitudes to the ground has been made for Mach numbers ranging from 1.3 to 6. The flight pressure signatures were recorded by microphones positioned at ground level near the groundtrack, whereas the wind tunnel signatures were measured during a test of a 0.0041-scale model Orbiter. The agreement between overpressure estimates based on wind tunnel data using preliminary flight trajectory data and oscillograph traces from ground measurements appears reasonable at this time for the range of Mach numbers considered. More detailed studies using final flight trajectory data and digitized ground measured data will be performed.

The terrain signatures of administrative units: a tool for environmental assessment.

PubMed

Miliaresis, George Ch

2009-03-01

The quantification of knowledge related to the terrain and the landuse/landcover of administrative units in Southern Greece (Peloponnesus) is performed from the CGIAR-CSI SRTM digital elevation model and the CORINE landuse/landcover database. Each administrative unit is parametrically represented by a set of attributes related to its relief. Administrative units are classified on the basis of K-means cluster analysis in an attempt to see how they are organized into groups and cluster derived geometric signatures are defined. Finally each cluster is parametrically represented on the basis of the occurrence of the Corine landuse/landcover classes included and thus, landcover signatures are derived. The geometric and the landuse/landcover signatures revealed a terrain dependent landuse/landcover organization that was used in the assessment of the forest fires impact at moderate resolution scale.

Blood Based Biomarkers of Early Onset Breast Cancer

DTIC Science & Technology

2016-12-01

discretizes the data, and also using logistic elastic net – a form of linear regression - we were unable to build a classifier that could accurately...classifier for differentiating cases from controls off discretized data. The first pass analysis demonstrated a 35 gene signature that differentiated...to the discretized data for mRNA gene signature, the samples used to “train” were also included in the final samples used to “test” the algorithm

Atmospheric chemical transport based on high-resolution model-derived winds: A case study

NASA Astrophysics Data System (ADS)

Hannan, John R.; Fuelberg, Henry E.; Thompson, Anne M.; Bieberbach, George; Knabb, Richard D.; Kondo, Yutaka; Anderson, Bruce E.; Browell, Edward V.; Gregory, Gerald L.; Sachse, Glen W.; Singh, Hanwant B.

2000-02-01

Flight 10 of NASA's Subsonic Assessment (SASS) Ozone and Nitrogen Oxide Experiment (SONEX) extended southwest of Lajes, Azores. A variety of chemical signatures was encountered. These signatures are examined in detail, relating them to meteorological data from a high-resolution numerical model having a horizontal grid spacing of 30 and 90 km with 26 vertical levels. The meteorological output at hourly intervals is used to create backward trajectories from the locations of the chemical signatures. Four major categories of chemical signatures are discussed: stratospheric, lightning, continental pollution, and a mixed chemical layer. The strong stratospheric signal is encountered just south of the Azores in a region of depressed tropopause height. Three chemical signatures at different altitudes in the upper troposphere are attributed to lightning. Backward trajectories from these signatures extend to locations of cloud-to-ground lightning. Specifically, results show that the trajectories pass over regions of lightning 1-2 days earlier over the eastern Gulf of Mexico and off the southeast coast of the United States. The lowest leg of the flight exhibits a chemical signature consistent with continental pollution. Trajectories from this signature are found to pass over the highly populated Northeast Corridor of the United States. Surface-based pollution apparently is lofted to the altitudes of the trajectories by convective clouds along the East Coast that did not contain lightning. Finally, a mixed layer is described. Its chemical signature is intermediate to those of lightning and continental pollution. Backward trajectories from this layer pass between the trajectories of the lightning and pollution signatures. Thus they likely are impacted by both sources.

Using CFD Surface Solutions to Shape Sonic Boom Signatures Propagated from Off-Body Pressure

NASA Technical Reports Server (NTRS)

Ordaz, Irian; Li, Wu

2013-01-01

The conceptual design of a low-boom and low-drag supersonic aircraft remains a challenge despite significant progress in recent years. Inverse design using reversed equivalent area and adjoint methods have been demonstrated to be effective in shaping the ground signature propagated from computational fluid dynamics (CFD) off-body pressure distributions. However, there is still a need to reduce the computational cost in the early stages of design to obtain a baseline that is feasible for low-boom shaping, and in the search for a robust low-boom design over the entire sonic boom footprint. The proposed design method addresses the need to reduce the computational cost for robust low-boom design by using surface pressure distributions from CFD solutions to shape sonic boom ground signatures propagated from CFD off-body pressure.

“Neuropathology of amyotrophic lateral sclerosis and its variants”

PubMed Central

Saberi, Shahram; Stauffer, Jennifer E.; Schulte, Derek J.; Ravits, John

2015-01-01

Summary Amyotrophic lateral sclerosis (ALS) is a clinical syndrome named for its neuropathological hallmark: degeneration of motor neurons in the spinal anterior horn and motor cortex and loss of axons in the lateral columns of the spinal cord. The signature neuropathological molecular signature common to almost all sporadic ALS and most familial ALS is TDP-43 immunoreactive neuronal cytoplasmic inclusions. The neuropathological and molecular neuropathological features of ALS variants primarly lateral sclerosis and progressive muscular atrophy are less certain, but also appear to share the primary features of ALS. A number of genetic causes including mutations in SOD1, FUS, and C9orf72 comprise a disease spectrum and all demonstrate distinctive molecular and neuropathological signatures. Neuropathology will continue to play to a key role in solving the puzzle of ALS pathogenesis. PMID:26515626

Compound-Specific Isotope Analysis of Amino Acids for Stardust-Returned Samples

NASA Technical Reports Server (NTRS)

Cook, Jamie; Elsila, Jamie E.; Stern J. C.; Glavin, D. P.; Dworkin, J. P.

2008-01-01

Significant portions of the early Earth's prebiotic organic inventory , including amino acids, could have been delivered to the Earth's sur face by comets and their fragments. Analysis of comets via spectrosc opic observations has identified many organic molecules, including me thane, ethane, arnmonia, cyanic acid, formaldehyde, formamide, acetal ehyde, acetonitrile, and methanol. Reactions between these identifie d molecules could allow the formation of more complex organics such a s amino acids. Isotopic analysis could reveal whether an extraterrest rial signature is present in the Stardust-exposed amines and amino ac ids. Although bulk isotopic analysis would be dominated by the EACA contaminant's terrestrial signature, compoundspecific isotope analysi s (CSIA) could determine the signature of each of the other individua l amines. Here, we report on progress made towards CSIA of the amino acids glycine and EACA in Stardustreturned samples.

Planetary radar studies. [radar mapping of the Moon and radar signatures of lunar and Venus craters

NASA Technical Reports Server (NTRS)

Thompson, T. W.; Cutts, J. A.

1981-01-01

Progress made in studying the evolution of Venusian craters and the evolution of infrared and radar signatures of lunar crater interiors is reported. Comparison of radar images of craters on Venus and the Moon present evidence for a steady state Venus crater population. Successful observations at the Arecibo Observatory yielded good data on five nights when data for a mix of inner and limb areas were acquired. Lunar craters with radar bright ejects are discussed. An overview of infrared radar crater catalogs in the data base is included.

Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

PubMed Central

Strell, Carina; Rundqvist, Helene

2012-01-01

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed. PMID:22509805

Receiver Operating Characteristic curves of the seismo-ionospheric precursors in GIM TEC associated with magnitude greater than 6.0 earthquakes in China during 1998-2013.

NASA Astrophysics Data System (ADS)

Huang, C. H.; Chen, Y. I.; Liu, J. Y. G.; Huang, Y. H.

2014-12-01

Statistical evidence of the Seismo-Ionospheric Precursors (SIPs) is reported by statistically investigating the relationship between the Total Electron Content (TEC) in Global Ionosphere Map (GIM) and 56 M≥6.0 earthquakes during 1998-2013 in China. A median-based method and a z test are employed to detect the overall earthquake signatures. It is found that a reduction of positive signatures and an enhancement of negative signatures appear simultaneously on 3-5 days prior to the earthquakes in China. Finally, receiver operating characteristic (ROC) curves are used to measure the power of TEC for predicting M≥6.0 earthquakes in China.

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes.

PubMed

Axelsson, Annika S; Tubbs, Emily; Mecham, Brig; Chacko, Shaji; Nenonen, Hannah A; Tang, Yunzhao; Fahey, Jed W; Derry, Jonathan M J; Wollheim, Claes B; Wierup, Nils; Haymond, Morey W; Friend, Stephen H; Mulder, Hindrik; Rosengren, Anders H

2017-06-14

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Focused and Steady-State Characteristics of Shaped Sonic Boom Signatures: Prediction and Analysis

NASA Technical Reports Server (NTRS)

Maglieri, Domenic J.; Bobbitt, Percy J.; Massey, Steven J.; Plotkin, Kenneth J.; Kandil, Osama A.; Zheng, Xudong

2011-01-01

The objective of this study is to examine the effect of flight, at off-design conditions, on the propagated sonic boom pressure signatures of a small "low-boom" supersonic aircraft. The amplification, or focusing, of the low magnitude "shaped" signatures produced by maneuvers such as the accelerations from transonic to supersonic speeds, climbs, turns, pull-up and pushovers is the concern. To analyze these effects, new and/or improved theoretical tools have been developed, in addition to the use of existing methodology. Several shaped signatures are considered in the application of these tools to the study of selected maneuvers and off-design conditions. The results of these applications are reported in this paper as well as the details of the new analytical tools. Finally, the magnitude of the focused boom problem for "low boom" supersonic aircraft designs has been more accurately quantified and potential "mitigations" suggested. In general, "shaped boom" signatures, designed for cruise flight, such as asymmetric and symmetric flat-top and initial-shock ramp waveforms retain their basic shape during transition flight. Complex and asymmetric and symmetric initial shock ramp waveforms provide lower magnitude focus boom levels than N-waves or asymmetric and symmetric flat-top signatures.

Rotation, scale, and translation invariant pattern recognition using feature extraction

NASA Astrophysics Data System (ADS)

Prevost, Donald; Doucet, Michel; Bergeron, Alain; Veilleux, Luc; Chevrette, Paul C.; Gingras, Denis J.

1997-03-01

A rotation, scale and translation invariant pattern recognition technique is proposed.It is based on Fourier- Mellin Descriptors (FMD). Each FMD is taken as an independent feature of the object, and a set of those features forms a signature. FMDs are naturally rotation invariant. Translation invariance is achieved through pre- processing. A proper normalization of the FMDs gives the scale invariance property. This approach offers the double advantage of providing invariant signatures of the objects, and a dramatic reduction of the amount of data to process. The compressed invariant feature signature is next presented to a multi-layered perceptron neural network. This final step provides some robustness to the classification of the signatures, enabling good recognition behavior under anamorphically scaled distortion. We also present an original feature extraction technique, adapted to optical calculation of the FMDs. A prototype optical set-up was built, and experimental results are presented.

A novel algorithm for simplification of complex gene classifiers in cancer

PubMed Central

Wilson, Raphael A.; Teng, Ling; Bachmeyer, Karen M.; Bissonnette, Mei Lin Z.; Husain, Aliya N.; Parham, David M.; Triche, Timothy J.; Wing, Michele R.; Gastier-Foster, Julie M.; Barr, Frederic G.; Hawkins, Douglas S.; Anderson, James R.; Skapek, Stephen X.; Volchenboum, Samuel L.

2013-01-01

The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing fifty-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm can distill this complex classifier down to two or three features with equal discrimination. We validated the two-gene signatures using three separate and distinct data sets, including one that uses degraded RNA extracted from formalin-fixed, paraffin-embedded material. Finally, to demonstrate the generalizability of our algorithm, we applied it to a lung cancer data set to find minimal gene signatures that can distinguish survival. Our approach can easily be generalized and coupled to existing technical platforms to facilitate the discovery of simplified signatures that are ready for routine clinical use. PMID:23913937

Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma.

PubMed

Mario Gonzalez-Meljem, Jose; Haston, Scott; Carreno, Gabriela; Apps, John R; Pozzi, Sara; Stache, Christina; Kaushal, Grace; Virasami, Alex; Panousopoulos, Leonidas; Neda Mousavy-Gharavy, Seyedeh; Guerrero, Ana; Rashid, Mamunur; Jani, Nital; Goding, Colin R; Jacques, Thomas S; Adams, David J; Gil, Jesus; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

2017-11-28

Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion.

SU-E-E-02: Dashboard for Tracking Physics Resident Progress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, SJ

2014-06-01

Purpose: Design a system to easily and securely track the progress of medical physics residents through their residency. Paper sign-offs while offering a real signature are not easily updated or summarized. A resident or mentor needs to be able to quickly assess what the current assignments are, what are overdue, and whether the resident is on track to complete all the tasks in a timely fashion. An electronic version can accomplish all these goals. Methods: An electronic dashboard was created in excel to not only house the tasks and sign-off but to succinctly summarize the residents progress. The first tabmore » contains the dashboard which displays tables of the progress of the residents in each rotation, their current task, and overdue tasks. It also displays the last meetings with the residents, and timeline of important items, and a burn-down chart of the remaining tasks. This are all tied to the data and current date which auto fills the tables. The second tab contains the data. This is comprised of lists of rotations and their associated tasks along with their due dates. A signature column was also created which is password protected but allows special subset users i.e. mentors to alter without using a password. Results: The dashboard has allowed residents to better track their progress and tells them what they should be working on. It has also allowed the mentors and the program director to rapid assess their progress. Conclusion: The dashboard is successful and has been created to allow easy addition and subtraction of required tasks as the residency evolves. The next step is to create a web app version of the excel sheet with logins.« less

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

PubMed

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

Gene Expression Profiling in BRAF-Mutated Melanoma Reveals Patient Subgroups with Poor Outcomes to Vemurafenib That May Be Overcome by Cobimetinib Plus Vemurafenib.

PubMed

Wongchenko, Matthew J; McArthur, Grant A; Dréno, Brigitte; Larkin, James; Ascierto, Paolo A; Sosman, Jeffrey; Andries, Luc; Kockx, Mark; Hurst, Stephen D; Caro, Ivor; Rooney, Isabelle; Hegde, Priti S; Molinero, Luciana; Yue, Huibin; Chang, Ilsung; Amler, Lukas; Yan, Yibing; Ribas, Antoni

2017-09-01

Purpose: The association of tumor gene expression profiles with progression-free survival (PFS) outcomes in patients with BRAF V600 -mutated melanoma treated with vemurafenib or cobimetinib combined with vemurafenib was evaluated. Experimental Design: Gene expression of archival tumor samples from patients in four trials (BRIM-2, BRIM-3, BRIM-7, and coBRIM) was evaluated. Genes significantly associated with PFS ( P < 0.05) were identified by univariate Cox proportional hazards modeling, then subjected to unsupervised hierarchical clustering, principal component analysis, and recursive partitioning to develop optimized gene signatures. Results: Forty-six genes were identified as significantly associated with PFS in both BRIM-2 ( n = 63) and the vemurafenib arm of BRIM-3 ( n = 160). Two distinct signatures were identified: cell cycle and immune. Among vemurafenib-treated patients, the cell-cycle signature was associated with shortened PFS compared with the immune signature in the BRIM-2/BRIM-3 training set [hazard ratio (HR) 1.8; 95% confidence interval (CI), 1.3-2.6, P = 0.0001] and in the coBRIM validation set ( n = 101; HR, 1.6; 95% CI, 1.0-2.5; P = 0.08). The adverse impact of the cell-cycle signature on PFS was not observed in patients treated with cobimetinib combined with vemurafenib ( n = 99; HR, 1.1; 95% CI, 0.7-1.8; P = 0.66). Conclusions: In vemurafenib-treated patients, the cell-cycle gene signature was associated with shorter PFS. However, in cobimetinib combined with vemurafenib-treated patients, both cell cycle and immune signature subgroups had comparable PFS. Cobimetinib combined with vemurafenib may abrogate the adverse impact of the cell-cycle signature. Clin Cancer Res; 23(17); 5238-45. ©2017 AACR . ©2017 American Association for Cancer Research.

42 CFR 485.638 - Conditions of participation: Clinical records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... clinical laboratory services, and consultative findings; (iii) All orders of doctors of medicine or osteopathy or other practitioners, reports of treatments and medications, nursing notes and documentation of... graphics, progress notes describing the patient's response to treatment; and (iv) Dated signatures of the...

Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

PubMed Central

Lau, Allison N; Curtis, Stephen J; Fillmore, Christine M; Rowbotham, Samuel P; Mohseni, Morvarid; Wagner, Darcy E; Beede, Alexander M; Montoro, Daniel T; Sinkevicius, Kerstin W; Walton, Zandra E; Barrios, Juliana; Weiss, Daniel J; Camargo, Fernando D; Wong, Kwok-Kin; Kim, Carla F

2014-01-01

Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease. PMID:24497554

MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.

PubMed

Olson, Peter; Lu, Jun; Zhang, Hao; Shai, Anny; Chun, Matthew G; Wang, Yucheng; Libutti, Steven K; Nakakura, Eric K; Golub, Todd R; Hanahan, Douglas

2009-09-15

While altered expression of microRNAs (miRs) in tumors has been well documented, it remains unclear how the miR transcriptome intersects neoplastic progression. By profiling the miR transcriptome we identified miR expression signatures associated with steps in tumorigenesis and the acquisition of hallmark capabilities in a prototypical mouse model of cancer. Metastases and a rare subset of primary tumors shared a distinct miR signature, implicating a discrete lineage for metastatic tumors. The miR-200 family is strongly down-regulated in metastases and met-like primary tumors, thereby relieving repression of the mesenchymal transcription factor Zeb1, which in turn suppresses E-cadherin. Treatment with a clinically approved angiogenesis inhibitor normalized angiogenic signature miRs in primary tumors, while altering expression of metastatic signature miRs similarly to liver metastases, suggesting their involvement in adaptive resistance to anti-angiogenic therapy via enhanced metastasis. Many of the miR changes associated with specific stages and hallmark capabilities in the mouse model are similarly altered in human tumors, including cognate pancreatic neuroendocrine tumors, implying a generality.

Blood-Based Gene Expression Profiles Models for Classification of Subsyndromal Symptomatic Depression and Major Depressive Disorder

PubMed Central

Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

2012-01-01

Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell–derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls. PMID:22348066

Atmospheric Chemical Transport Based on High Resolution Model- Derived Winds: A Case Study

NASA Technical Reports Server (NTRS)

Hannan, John R.; Fuelberg, Henry E.; Thompson, Anne M.; Bieberbach, George, Jr.; Knabb, Richard D.; Kondo, Yutaka; Anderson, Bruce E.; Browell, Edward V.; Gregory, Gerald L.; Sachse, Glen;

Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis

PubMed Central

Sweiss, Nadera J.; Chen, Edward S.; Moller, David R.; Knox, Kenneth S.; Ma, Shwu-Fan; Wade, Michael S.; Noth, Imre; Machado, Roberto F.; Garcia, Joe G. N.

2012-01-01

Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ∼20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n = 35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis. PMID:22984568

Genetic signatures of natural selection in a model invasive ascidian

NASA Astrophysics Data System (ADS)

Lin, Yaping; Chen, Yiyong; Yi, Changho; Fong, Jonathan J.; Kim, Won; Rius, Marc; Zhan, Aibin

2017-03-01

Invasive species represent promising models to study species’ responses to rapidly changing environments. Although local adaptation frequently occurs during contemporary range expansion, the associated genetic signatures at both population and genomic levels remain largely unknown. Here, we use genome-wide gene-associated microsatellites to investigate genetic signatures of natural selection in a model invasive ascidian, Ciona robusta. Population genetic analyses of 150 individuals sampled in Korea, New Zealand, South Africa and Spain showed significant genetic differentiation among populations. Based on outlier tests, we found high incidence of signatures of directional selection at 19 loci. Hitchhiking mapping analyses identified 12 directional selective sweep regions, and all selective sweep windows on chromosomes were narrow (~8.9 kb). Further analyses indentified 132 candidate genes under selection. When we compared our genetic data and six crucial environmental variables, 16 putatively selected loci showed significant correlation with these environmental variables. This suggests that the local environmental conditions have left significant signatures of selection at both population and genomic levels. Finally, we identified “plastic” genomic regions and genes that are promising regions to investigate evolutionary responses to rapid environmental change in C. robusta.

Signature simulation of mixed materials

NASA Astrophysics Data System (ADS)

Carson, Tyler D.; Salvaggio, Carl

2015-05-01

Soil target signatures vary due to geometry, chemical composition, and scene radiometry. Although radiative transfer models and function-fit physical models may describe certain targets in limited depth, the ability to incorporate all three signature variables is difficult. This work describes a method to simulate the transient signatures of soil by first considering scene geometry synthetically created using 3D physics engines. Through the assignment of spectral data from the Nonconventional Exploitation Factors Data System (NEFDS), the synthetic scene is represented as a physical mixture of particles. Finally, first principles radiometry is modeled using the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model. With DIRSIG, radiometric and sensing conditions were systematically manipulated to produce and record goniometric signatures. The implementation of this virtual goniometer allows users to examine how a target bidirectional reflectance distribution function (BRDF) will change with geometry, composition, and illumination direction. By using 3D computer graphics models, this process does not require geometric assumptions that are native to many radiative transfer models. It delivers a discrete method to circumnavigate the significant cost of time and treasure associated with hardware-based goniometric data collections.

77 FR 43370 - TUV Rheinland of North America, Inc.; Application for Expansion of Recognition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... scope of recognition has three elements: (1) The type of products the NRTL may test, with each type... Assistant Secretary will make the final decision on granting the application and, in making this decision... notice of this final decision in the Federal Register. Authority and Signature David Michaels, Ph.D., MPH...

Evaluation of plasma proteomic data for Alzheimer disease state classification and for the prediction of progression from mild cognitive impairment to Alzheimer disease.

PubMed

Llano, Daniel A; Devanarayan, Viswanath; Simon, Adam J

2013-01-01

Previous studies that have examined the potential for plasma markers to serve as biomarkers for Alzheimer disease (AD) have studied single analytes and focused on the amyloid-β and τ isoforms and have failed to yield conclusive results. In this study, we performed a multivariate analysis of 146 plasma analytes (the Human DiscoveryMAP v 1.0 from Rules-Based Medicine) in 527 subjects with AD, mild cognitive impairment (MCI), or cognitively normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative database. We identified 4 different proteomic signatures, each using 5 to 14 analytes, that differentiate AD from control patients with sensitivity and specificity ranging from 74% to 85%. Five analytes were common to all 4 signatures: apolipoprotein A-II, apolipoprotein E, serum glutamic oxaloacetic transaminase, α-1-microglobulin, and brain natriuretic peptide. None of the signatures adequately predicted progression from MCI to AD over a 12- and 24-month period. A new panel of analytes, optimized to predict MCI to AD conversion, was able to provide 55% to 60% predictive accuracy. These data suggest that a simple panel of plasma analytes may provide an adjunctive tool to differentiate AD from controls, may provide mechanistic insights to the etiology of AD, but cannot adequately predict MCI to AD conversion.

Epigenetic signatures of invasive status in populations of marine invertebrates

NASA Astrophysics Data System (ADS)

Ardura, Alba; Zaiko, Anastasija; Morán, Paloma; Planes, Serge; Garcia-Vazquez, Eva

2017-02-01

Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced. Decreased methylation was interpreted as a rapid way of increasing phenotypic plasticity that would help invasive populations to thrive. This epigenetic signature of early invasion was stronger than the expected environmental signature of environmental stress in younger populations sampled from ports, otherwise detected in a much older population (>90 year old) of the also invasive tubeworm Ficopomatus enigmaticus established in similar locations. Higher epigenetic than genetic diversity found in X. securis was confirmed from F. enigmaticus samples. As reported for introduced plants and vertebrates, epigenetic variation could compensate for relatively lower genetic variation caused by founder effects. These phenomena were compared with epigenetic mechanisms involved in metastasis, as parallel processes of community (biological invasion) and organism (cancer) invasions.

A miRNA Signature for Cognitive Deficits and Alcohol Use Disorder in Persons Living with HIV/AIDS

PubMed Central

Wyczechowska, Dorota; Lin, Hui-Yi; LaPlante, Andrea; Jeansonne, Duane; Lassak, Adam; Parsons, Christopher H.; Molina, Patricia E.; Peruzzi, Francesca

2017-01-01

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with alcohol use disorder (AUD) at LSU Health Sciences Center (LSUHSC). The results show that AUD is a potential confounding factor for the miRNAs associated with cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA signature associated with cognitive impairment in an independent cohort of PLWHA using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) program. Despite differences between the two cohorts in socioeconomic status, AUD, and likely misuse of illicit or prescription drugs, we validated a miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples. PMID:29187813

Quantum random oracle model for quantum digital signature

NASA Astrophysics Data System (ADS)

Shang, Tao; Lei, Qi; Liu, Jianwei

2016-10-01

The goal of this work is to provide a general security analysis tool, namely, the quantum random oracle (QRO), for facilitating the security analysis of quantum cryptographic protocols, especially protocols based on quantum one-way function. QRO is used to model quantum one-way function and different queries to QRO are used to model quantum attacks. A typical application of quantum one-way function is the quantum digital signature, whose progress has been hampered by the slow pace of the experimental realization. Alternatively, we use the QRO model to analyze the provable security of a quantum digital signature scheme and elaborate the analysis procedure. The QRO model differs from the prior quantum-accessible random oracle in that it can output quantum states as public keys and give responses to different queries. This tool can be a test bed for the cryptanalysis of more quantum cryptographic protocols based on the quantum one-way function.

Peripheral Blood Signatures of Lead Exposure

PubMed Central

LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

2011-01-01

Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

Deep Habits: Workshop as Critique in Creative Writing

ERIC Educational Resources Information Center

Stukenberg, Jill

2017-01-01

The creative writing workshop, involving peer critique of manuscripts in progress, is deeply connected to many writerly habits of mind. As such, this article examines workshop as a signature pedagogy in creative writing. Through workshop, students develop awareness of their readers, understanding of how texts are created by readers and through…

Advanced Cancer Genomics Institute: Genetic Signatures and Therapeutic Targets in Cancer Progression

DTIC Science & Technology

2015-04-01

ORGANIZATION REPORT NUMBER Roswell Park Cancer Institute Elm and Carlton Streets Buffalo, NY 14263 9. SPONSORING / MONITORING AGENCY NAME(S) AND...AD- and CR-CaP cases. Roswell Park already has produced a 5- slide tumor microarray containing 722 CaP/matched normal biopsy samples for follow

Comparison of transcriptomic signature of post-Chernobyl and postradiotherapy thyroid tumors.

PubMed

Ory, Catherine; Ugolin, Nicolas; Hofman, Paul; Schlumberger, Martin; Likhtarev, Illya A; Chevillard, Sylvie

2013-11-01

We previously identified two highly discriminating and predictive radiation-induced transcriptomic signatures by comparing series of sporadic and postradiotherapy thyroid tumors (322-gene signature), and by reanalyzing a previously published data set of sporadic and post-Chernobyl thyroid tumors (106-gene signature). The aim of the present work was (i) to compare the two signatures in terms of gene expression deregulations and molecular features/pathways, and (ii) to test the capacity of the postradiotherapy signature in classifying the post-Chernobyl series of tumors and reciprocally of the post-Chernobyl signature in classifying the postradiotherapy-induced tumors. We now explored if postradiotherapy and post-Chernobyl papillary thyroid carcinomas (PTC) display common molecular features by comparing molecular pathways deregulated in the two tumor series, and tested the potential of gene subsets of the postradiotherapy signature to classify the post-Chernobyl series (14 sporadic and 12 post-Chernobyl PTC), and reciprocally of gene subsets of the post-Chernobyl signature to classify the postradiotherapy series (15 sporadic and 12 postradiotherapy PTC), by using conventional principal component analysis. We found that the five genes common to the two signatures classified the learning/training tumors (used to search these signatures) of both the postradiotherapy (seven PTC) and the post-Chernobyl (six PTC) thyroid tumor series as compared with the sporadic tumors (seven sporadic PTC in each series). Importantly, these five genes were also effective for classifying independent series of postradiotherapy (five PTC) and post-Chernobyl (six PTC) tumors compared to independent series of sporadic tumors (eight PTC and six PTC respectively; testing tumors). Moreover, part of each postradiotherapy (32 genes) and post-Chernobyl signature (16 genes) cross-classified the respective series of thyroid tumors. Finally, several molecular pathways deregulated in post-Chernobyl tumors matched those found to be deregulated in postradiotherapy tumors. Overall, our data suggest that thyroid tumors that developed following either external exposure or internal (131)I contamination shared common molecular features, related to DNA repair, oxidative and endoplasmic reticulum stresses, allowing their classification as radiation-induced tumors in comparison with sporadic counterparts, independently of doses and dose rates, which suggests there may be a "general" radiation-induced signature of thyroid tumors.

Grant Closeout Requirements and Reports

Cancer.gov

Requirements and reports to comply with grant closeout, including Final Federal Financial Report (FFR, SF425); Final Research Performance Progress Report (FRPPR); Interim Research Performance Progress Report (IRPPR); Final Invention Statement (FIS, HHS

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis.

PubMed

Rajamani, Deepa; Bhasin, Manoj K

2016-05-03

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression. Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis. Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities. It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

PubMed

Jin, Bao-Feng; Yang, Fan; Ying, Xiao-Min; Gong, Lin; Hu, Shuo-Feng; Zhao, Qing; Liao, Yi-Da; Chen, Ke-Zhong; Li, Teng; Tai, Yan-Hong; Cao, Yuan; Li, Xiao; Huang, Yan; Zhan, Xiao-Yan; Qin, Xuan-He; Wu, Jin; Chen, Shuai; Guo, Sai-Sai; Zhang, Yu-Cheng; Chen, Jing; Shen, Dan-Hua; Sun, Kun-Kun; Chen, Lu; Li, Wei-Hua; Li, Ai-Ling; Wang, Na; Xia, Qing; Wang, Jun; Zhou, Tao

2018-03-06

Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Collider Signal II:. Missing ET Signatures and Dark Matter Connection

NASA Astrophysics Data System (ADS)

Baer, Howard

2010-08-01

These lectures give an overview of aspects of missing ET signatures from new physics at the LHC, along with their important connection to dark matter physics. Mostly, I will concentrate on supersymmetric (SUSY) sources of ɆT, but will also mention Little Higgs models with T-parity (LHT) and universal extra dimensions (UED) models with KK-parity. Lecture 1 covers SUSY basics, model building and spectra computation. Lecture 2 addresses sparticle production and decay mechanisms at hadron colliders and event generation. Lecture 3 covers SUSY signatures at LHC, along with LHT and UED signatures for comparison. In Lecture 4, I address the dark matter connection, and how direct and indirect dark matter searches, along with LHC collider searches, may allow us to both discover and characterize dark matter in the next several years. Finally, the interesting scenario of Yukawa-unified SUSY is examined; this case works best if the dark matter turns out to be a mixture of axion/axino states, rather than neutralinos.

Assessment of Gamma-Ray-Spectra Analysis Method Utilizing the Fireworks Algorithm for Various Error Measures

DOE PAGES

Alamaniotis, Miltiadis; Tsoukalas, Lefteri H.

2018-01-01

The analysis of measured data plays a significant role in enhancing nuclear nonproliferation mainly by inferring the presence of patterns associated with special nuclear materials. Among various types of measurements, gamma-ray spectra is the widest utilized type of data in nonproliferation applications. In this paper, a method that employs the fireworks algorithm (FWA) for analyzing gamma-ray spectra aiming at detecting gamma signatures is presented. In particular, FWA is utilized to fit a set of known signatures to a measured spectrum by optimizing an objective function, where non-zero coefficients express the detected signatures. FWA is tested on a set of experimentallymore » obtained measurements optimizing various objective functions—MSE, RMSE, Theil-2, MAE, MAPE, MAP—with results exhibiting its potential in providing highly accurate and precise signature detection. Finally and furthermore, FWA is benchmarked against genetic algorithms and multiple linear regression, showing its superiority over those algorithms regarding precision with respect to MAE, MAPE, and MAP measures.« less

New insight into the role of MMP14 in metabolic balance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Hidetoshi; Bhat, Ramray; Bruni-Cardoso, Alexandre

Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into anmore » unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism.« less

A signature of anisotropic cosmic-ray transport in the gamma-ray sky

NASA Astrophysics Data System (ADS)

Cerri, Silvio Sergio; Gaggero, Daniele; Vittino, Andrea; Evoli, Carmelo; Grasso, Dario

2017-10-01

A crucial process in Galactic cosmic-ray (CR) transport is the spatial diffusion due to the interaction with the interstellar turbulent magnetic field. Usually, CR diffusion is assumed to be uniform and isotropic all across the Galaxy. However, this picture is clearly inaccurate: several data-driven and theoretical arguments, as well as dedicated numerical simulations, show that diffusion exhibits highly anisotropic properties with respect to the direction of a background (ordered) magnetic field (i.e., parallel or perpendicular to it). In this paper we focus on a recently discovered anomaly in the hadronic CR spectrum inferred by the Fermi-LAT gamma-ray data at different positions in the Galaxy, i.e. the progressive hardening of the proton slope at low Galactocentric radii. We propose the idea that this feature can be interpreted as a signature of anisotropic diffusion in the complex Galactic magnetic field: in particular, the harder slope in the inner Galaxy is due, in our scenario, to the parallel diffusive escape along the poloidal component of the large-scale, regular, magnetic field. We implement this idea in a numerical framework, based on the DRAGON code, and perform detailed numerical tests on the accuracy of our setup. We discuss how the effect proposed depends on the relevant free parameters involved. Based on low-energy extrapolation of the few focused numerical simulations aimed at determining the scalings of the anisotropic diffusion coefficients, we finally present a set of plausible models that reproduce the behavior of the CR proton slopes inferred by gamma-ray data.

New insight into the role of MMP14 in metabolic balance

DOE PAGES

Mori, Hidetoshi; Bhat, Ramray; Bruni-Cardoso, Alexandre; ...

2016-07-13

Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into anmore » unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism.« less

The Metastasis Efficiency Modifier Ribosomal RNA Processing 1 Homolog B (RRP1B) Is a Chromatin-associated Factor*

PubMed Central

Crawford, Nigel P. S.; Yang, Hailiu; Mattaini, Katherine R.; Hunter, Kent W.

2009-01-01

There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1α and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure. PMID:19710015

A signature of anisotropic cosmic-ray transport in the gamma-ray sky

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cerri, Silvio Sergio; Grasso, Dario; Gaggero, Daniele

A crucial process in Galactic cosmic-ray (CR) transport is the spatial diffusion due to the interaction with the interstellar turbulent magnetic field. Usually, CR diffusion is assumed to be uniform and isotropic all across the Galaxy. However, this picture is clearly inaccurate: several data-driven and theoretical arguments, as well as dedicated numerical simulations, show that diffusion exhibits highly anisotropic properties with respect to the direction of a background (ordered) magnetic field (i.e., parallel or perpendicular to it). In this paper we focus on a recently discovered anomaly in the hadronic CR spectrum inferred by the Fermi-LAT gamma-ray data at differentmore » positions in the Galaxy, i.e. the progressive hardening of the proton slope at low Galactocentric radii. We propose the idea that this feature can be interpreted as a signature of anisotropic diffusion in the complex Galactic magnetic field: in particular, the harder slope in the inner Galaxy is due, in our scenario, to the parallel diffusive escape along the poloidal component of the large-scale, regular, magnetic field. We implement this idea in a numerical framework, based on the DRAGON code, and perform detailed numerical tests on the accuracy of our setup. We discuss how the effect proposed depends on the relevant free parameters involved. Based on low-energy extrapolation of the few focused numerical simulations aimed at determining the scalings of the anisotropic diffusion coefficients, we finally present a set of plausible models that reproduce the behavior of the CR proton slopes inferred by gamma-ray data.« less

SLIPPING MAGNETIC RECONNECTION, CHROMOSPHERIC EVAPORATION, IMPLOSION, AND PRECURSORS IN THE 2014 SEPTEMBER 10 X1.6-CLASS SOLAR FLARE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dudík, Jaroslav; Karlický, Marian; Dzifčáková, Elena

2016-05-20

We investigate the occurrence of slipping magnetic reconnection, chromospheric evaporation, and coronal loop dynamics in the 2014 September 10 X-class flare. Slipping reconnection is found to be present throughout the flare from its early phase. Flare loops are seen to slip in opposite directions toward both ends of the ribbons. Velocities of 20–40 km s{sup −1} are found within time windows where the slipping is well resolved. The warm coronal loops exhibit expanding and contracting motions that are interpreted as displacements due to the growing flux rope that subsequently erupts. This flux rope existed and erupted before the onset ofmore » apparent coronal implosion. This indicates that the energy release proceeds by slipping reconnection and not via coronal implosion. The slipping reconnection leads to changes in the geometry of the observed structures at the Interface Region Imaging Spectrograph slit position, from flare loop top to the footpoints in the ribbons. This results in variations of the observed velocities of chromospheric evaporation in the early flare phase. Finally, it is found that the precursor signatures, including localized EUV brightenings as well as nonthermal X-ray emission, are signatures of the flare itself, progressing from the early phase toward the impulsive phase, with the tether-cutting being provided by the slipping reconnection. The dynamics of both the flare and outlying coronal loops is found to be consistent with the predictions of the standard solar flare model in three dimensions.« less

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

PubMed Central

Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

2010-01-01

Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications.

PubMed

Sundararajan, Vignesh; Sarkar, Fazlul H; Ramasamy, Thamil Selvee

2018-06-01

Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules. This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

Extra Higgs boson and Z ' as portals to signatures of heavy neutrinos at the LHC

NASA Astrophysics Data System (ADS)

Accomando, Elena; Rose, Luigi Delle; Moretti, Stefano; Olaiya, Emmanuel; Shepherd-Themistocleous, Claire H.

2018-02-01

In this paper, we discuss the potential of observing heavy neutrino ( ν h ) signatures of a U(1) B- L enlarged Standard Model (SM) encompassing three heavy Majorana neutrinos alongside the known light neutrino states at the Large Hadron Collider (LHC). We exploit the theoretical decay via a heavy (non-SM-like) Higgs boson and Z ' production followed by ν h → l ± W ∓(∗) and ν h → ν l Z (∗) decays, ultimately yielding a 3 l + 2 j + E T miss signature and, depending upon how boosted the final state objects are, we define different possible selections aimed at improving the signal to background ratio in LHC Run 2 data for a wide range of heavy neutrino masses.

New Physics at the LHC: A Les Houches Report. Physics at Tev Colliders 2007 - New Physics Working Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooijmans, Gustaaf H.; /Columbia U.; Delgado, A.

2011-12-05

We present a collection of signatures for physics beyond the standard model that need to be explored at the LHC. The signatures are organized according to the experimental objects that appear in the final state, and in particular the number of high p{sub T} leptons. Our report, which includes brief experimental and theoretical reviews as well as original results, summarizes the activities of the 'New Physics' working group for the 'Physics at TeV Colliders' workshop (Les Houches, France, 11-29 June, 2007).

The Lagrange Points in a Binary Black Hole System: Applications to Electromagnetic Signatures

NASA Technical Reports Server (NTRS)

Schnittman, Jeremy

2010-01-01

We study the stability and evolution of the Lagrange points L_4 and L-5 in a black hole (BH) binary system, including gravitational radiation. We find that gas and stars can be shepherded in with the BH system until the final moments before merger, providing the fuel for a bright electromagnetic counterpart to a gravitational wave signal. Other astrophysical signatures include the ejection of hyper-velocity stars, gravitational collapse of globular clusters, and the periodic shift of narrow emission lines in AGN.

Integrated metagenomic data analysis demonstrates that a loss of diversity in oral microbiota is associated with periodontitis.

PubMed

Ai, Dongmei; Huang, Ruocheng; Wen, Jin; Li, Chao; Zhu, Jiangping; Xia, Li Charlie

2017-01-25

Periodontitis is an inflammatory disease affecting the tissues supporting teeth (periodontium). Integrative analysis of metagenomic samples from multiple periodontitis studies is a powerful way to examine microbiota diversity and interactions within host oral cavity. A total of 43 subjects were recruited to participate in two previous studies profiling the microbial community of human subgingival plaque samples using shotgun metagenomic sequencing. We integrated metagenomic sequence data from those two studies, including six healthy controls, 14 sites representative of stable periodontitis, 16 sites representative of progressing periodontitis, and seven periodontal sites of unknown status. We applied phylogenetic diversity, differential abundance, and network analyses, as well as clustering, to the integrated dataset to compare microbiological community profiles among the different disease states. We found alpha-diversity, i.e., mean species diversity in sites or habitats at a local scale, to be the single strongest predictor of subjects' periodontitis status (P < 0.011). More specifically, healthy subjects had the highest alpha-diversity, while subjects with stable sites had the lowest alpha-diversity. From these results, we developed an alpha-diversity logistic model-based naive classifier able to perfectly predict the disease status of the seven subjects with unknown periodontal status (not used in training). Phylogenetic profiling resulted in the discovery of nine marker microbes, and these species are able to differentiate between stable and progressing periodontitis, achieving an accuracy of 94.4%. Finally, we found that the reduction of negatively correlated species is a notable signature of disease progression. Our results consistently show a strong association between the loss of oral microbiota diversity and the progression of periodontitis, suggesting that metagenomics sequencing and phylogenetic profiling are predictive of early periodontitis, leading to potential therapeutic intervention. Our results also support a keystone pathogen-mediated polymicrobial synergy and dysbiosis (PSD) model to explain the etiology of periodontitis. Apart from P. gingivalis, we identified three additional keystone species potentially mediating the progression of periodontitis progression based on pathogenic characteristics similar to those of known keystone pathogens.

Resolving prokaryotic taxonomy without rRNA: longer oligonucleotide word lengths improve genome and metagenome taxonomic classification.

PubMed

Alsop, Eric B; Raymond, Jason

2013-01-01

Oligonucleotide signatures, especially tetranucleotide signatures, have been used as method for homology binning by exploiting an organism's inherent biases towards the use of specific oligonucleotide words. Tetranucleotide signatures have been especially useful in environmental metagenomics samples as many of these samples contain organisms from poorly classified phyla which cannot be easily identified using traditional homology methods, including NCBI BLAST. This study examines oligonucleotide signatures across 1,424 completed genomes from across the tree of life, substantially expanding upon previous work. A comprehensive analysis of mononucleotide through nonanucleotide word lengths suggests that longer word lengths substantially improve the classification of DNA fragments across a range of sizes of relevance to high throughput sequencing. We find that, at present, heptanucleotide signatures represent an optimal balance between prediction accuracy and computational time for resolving taxonomy using both genomic and metagenomic fragments. We directly compare the ability of tetranucleotide and heptanucleotide world lengths (tetranucleotide signatures are the current standard for oligonucleotide word usage analyses) for taxonomic binning of metagenome reads. We present evidence that heptanucleotide word lengths consistently provide more taxonomic resolving power, particularly in distinguishing between closely related organisms that are often present in metagenomic samples. This implies that longer oligonucleotide word lengths should replace tetranucleotide signatures for most analyses. Finally, we show that the application of longer word lengths to metagenomic datasets leads to more accurate taxonomic binning of DNA scaffolds and have the potential to substantially improve taxonomic assignment and assembly of metagenomic data.

The Role of microRNA miR-101 in Prostate Cancer Progression

DTIC Science & Technology

2011-09-01

13 signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 353, 1793-801. 18. Pallante , P., Visone...June; published online 31 July 2011; doi:10.1038/nbt.1914 © 2 01 1 N at u re A m er ic a, In c. A ll ri g h ts r es er ve d . nature...the design or funding of these studies. The other authors declare that they have no competing interests. Submitted 14 July 2010 Accepted 10 February

Genetic signatures of natural selection in a model invasive ascidian

PubMed Central

Lin, Yaping; Chen, Yiyong; Yi, Changho; Fong, Jonathan J.; Kim, Won; Rius, Marc; Zhan, Aibin

2017-01-01

Invasive species represent promising models to study species’ responses to rapidly changing environments. Although local adaptation frequently occurs during contemporary range expansion, the associated genetic signatures at both population and genomic levels remain largely unknown. Here, we use genome-wide gene-associated microsatellites to investigate genetic signatures of natural selection in a model invasive ascidian, Ciona robusta. Population genetic analyses of 150 individuals sampled in Korea, New Zealand, South Africa and Spain showed significant genetic differentiation among populations. Based on outlier tests, we found high incidence of signatures of directional selection at 19 loci. Hitchhiking mapping analyses identified 12 directional selective sweep regions, and all selective sweep windows on chromosomes were narrow (~8.9 kb). Further analyses indentified 132 candidate genes under selection. When we compared our genetic data and six crucial environmental variables, 16 putatively selected loci showed significant correlation with these environmental variables. This suggests that the local environmental conditions have left significant signatures of selection at both population and genomic levels. Finally, we identified “plastic” genomic regions and genes that are promising regions to investigate evolutionary responses to rapid environmental change in C. robusta. PMID:28266616

[Study of automatic marine oil spills detection using imaging spectroscopy].

PubMed

Liu, De-Lian; Han, Liang; Zhang, Jian-Qi

2013-11-01

To reduce artificial auxiliary works in oil spills detection process, an automatic oil spill detection method based on adaptive matched filter is presented. Firstly, the characteristics of reflectance spectral signature of C-H bond in oil spill are analyzed. And an oil spill spectral signature extraction model is designed by using the spectral feature of C-H bond. It is then used to obtain the reference spectral signature for the following oil spill detection step. Secondly, the characteristics of reflectance spectral signature of sea water, clouds, and oil spill are compared. The bands which have large difference in reflectance spectral signatures of the sea water, clouds, and oil spill are selected. By using these bands, the sea water pixels are segmented. And the background parameters are then calculated. Finally, the classical adaptive matched filter from target detection algorithms is improved and introduced for oil spill detection. The proposed method is applied to the real airborne visible infrared imaging spectrometer (AVIRIS) hyperspectral image captured during the deepwater horizon oil spill in the Gulf of Mexico for oil spill detection. The results show that the proposed method has, high efficiency, does not need artificial auxiliary work, and can be used for automatic detection of marine oil spill.

A VEGF-dependent gene signature enriched in mesenchymal ovarian cancer predicts patient prognosis.

PubMed

Yin, Xia; Wang, Xiaojie; Shen, Boqiang; Jing, Ying; Li, Qing; Cai, Mei-Chun; Gu, Zhuowei; Yang, Qi; Zhang, Zhenfeng; Liu, Jin; Li, Hongxia; Di, Wen; Zhuang, Guanglei

2016-08-08

We have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes. In patients who received bevacizumab therapy and showed partial response, the expressions of VDGs (summarized to yield VDGs scores) were markedly decreased in post-treatment biopsies compared with pre-treatment baselines. In contrast, VDGs scores were not significantly altered following bevacizumab treatment in patients with stable or progressive disease. Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was able to predict patient outcome. Correlation estimation of VDGs scores and molecular features revealed that VDGs was overrepresented in mesenchymal subtype and BRCA mutation carriers. These findings highlighted the prognostic role of VEGF-mediated angiogenesis in ovarian cancer, and proposed a VEGF-dependent gene signature as a molecular basis for developing novel diagnostic strategies to aid patient selection for VEGF-targeted agents.

A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma

PubMed Central

Navarro, Alfons; Díaz, Tania; Tovar, Natalia; Pedrosa, Fabiola; Tejero, Rut; Cibeira, María Teresa; Magnano, Laura; Rosiñol, Laura; Monzó, Mariano; Bladé, Joan; de Larrea, Carlos Fernández

2015-01-01

We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT. Supervised analysis identified a differentially expressed 14-microRNA signature. The differential expression of miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017) and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual assays. In addition, high levels of miR-25 were related to the presence of oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9 years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA signature with potential as a diagnostic and prognostic tool in MM. PMID:25593199

On the information content of hydrological signatures and their relationship to catchment attributes

NASA Astrophysics Data System (ADS)

Addor, Nans; Clark, Martyn P.; Prieto, Cristina; Newman, Andrew J.; Mizukami, Naoki; Nearing, Grey; Le Vine, Nataliya

2017-04-01

Hydrological signatures, which are indices characterizing hydrologic behavior, are increasingly used for the evaluation, calibration and selection of hydrological models. Their key advantage is to provide more direct insights into specific hydrological processes than aggregated metrics (e.g., the Nash-Sutcliffe efficiency). A plethora of signatures now exists, which enable characterizing a variety of hydrograph features, but also makes the selection of signatures for new studies challenging. Here we propose that the selection of signatures should be based on their information content, which we estimated using several approaches, all leading to similar conclusions. To explore the relationship between hydrological signatures and the landscape, we extended a previously published data set of hydrometeorological time series for 671 catchments in the contiguous United States, by characterizing the climatic conditions, topography, soil, vegetation and stream network of each catchment. This new catchment attributes data set will soon be in open access, and we are looking forward to introducing it to the community. We used this data set in a data-learning algorithm (random forests) to explore whether hydrological signatures could be inferred from catchment attributes alone. We find that some signatures can be predicted remarkably well by random forests and, interestingly, the same signatures are well captured when simulating discharge using a conceptual hydrological model. We discuss what this result reveals about our understanding of hydrological processes shaping hydrological signatures. We also identify which catchment attributes exert the strongest control on catchment behavior, in particular during extreme hydrological events. Overall, climatic attributes have the most significant influence, and strongly condition how well hydrological signatures can be predicted by random forests and simulated by the hydrological model. In contrast, soil characteristics at the catchment scale are not found to be significant predictors by random forests, which raises questions on how to best use soil data for hydrological modeling, for instance for parameter estimation. We finally demonstrate that signatures with high spatial variability are poorly captured by random forests and model simulations, which makes their regionalization delicate. We conclude with a ranking of signatures based on their information content, and propose that the signatures with high information content are best suited for model calibration, model selection and understanding hydrologic similarity.

The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil.

PubMed

Sánchez-Aragó, María; Cuezva, José M

2011-02-08

Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H+-ATPase (β-F1-ATPase). The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU). The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the bioenergetic signature directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the in vitro cell-death responses associated with 3BrP, IA and 5-FU, the in vivo tumor regression activities of these agents were comparable. Overall, we suggest that the determination of the bioenergetic signature of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.

Recent progress in the design and clinical development of electronic-nose technologies

Treesearch

Dan Wilson

2016-01-01

Electronic-nose (e-nose) devices are instruments designed to detect and discriminate between precise complex gaseous mixtures of volatile organic compounds derived from specific organic sources, such as clinical test samples from patients, based on electronic aroma signature patterns (distinct digital sensor responses) resulting from the combined outputs of a...

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

USDA-ARS?s Scientific Manuscript database

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

Biomass power for rural development. Technical progress report, October 1--December 31, 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

The focus of the DOE/USDA sponsored biomass power for rural development project is to develop commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC).more » Phase-2 of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is underway. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill Power Station. Phase-3 will represent fullscale commercialization of the energy crop and power generation on a sustainable basis. During the fourth quarter of 1997 the Consortium submitted a Phase-2 proposal. A few of the other more important milestones are outlined below. The first quarter of 1998 will be dominated by pre-planting activity in the spring.« less

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

DOE PAGES

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; ...

2016-05-02

Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, anothermore » with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.« less

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan

Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, anothermore » with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.« less

Landscape of somatic mutations in 560 breast cancer whole genome sequences

PubMed Central

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B; Morganella, Sandro; Aure, Miriam R.; Lingjærde, Ole Christian; Langerød, Anita; Ringnér, Markus; Ahn, Sung-Min; Boyault, Sandrine; Brock, Jane E.; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A.; Gerstung, Moritz; Hooijer, Gerrit KJ; Jang, Se Jin; Jones, David R.; Kim, Hyung-Yong; King, Tari A.; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong-Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O’Meara, Sarah; Pauporté, Iris; Pivot, Xavier; Purdie, Colin A.; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-González, F. Germán; Romieu, Gilles; Sieuwerts, Anieta M.; Simpson, Peter T; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G.; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; van’t Veer, Laura; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Åke; Ueno, Naoto T; Sotiriou, Christos; Viari, Alain; Futreal, P. Andrew; Campbell, Peter J; Span, Paul N.; Van Laere, Steven; Lakhani, Sunil R; Eyfjord, Jorunn E.; Thompson, Alastair M.; Birney, Ewan; Stunnenberg, Hendrik G; van de Vijver, Marc J; Martens, John W.M.; Børresen-Dale, Anne-Lise; Richardson, Andrea L.; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

2016-01-01

We analysed whole genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. 93 protein-coding cancer genes carried likely driver mutations. Some non-coding regions exhibited high mutation frequencies but most have distinctive structural features probably causing elevated mutation rates and do not harbour driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed 12 base substitution and six rearrangement signatures. Three rearrangement signatures, characterised by tandem duplications or deletions, appear associated with defective homologous recombination based DNA repair: one with deficient BRCA1 function; another with deficient BRCA1 or BRCA2 function; the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer. PMID:27135926

Theoretical Characterization of Visual Signatures and Calculation of Approximate Global Harmonic Frequency Scaling Factors

NASA Astrophysics Data System (ADS)

Kashinski, D. O.; Nelson, R. G.; Chase, G. M.; di Nallo, O. E.; Byrd, E. F. C.

2016-05-01

We are investigating the accuracy of theoretical models used to predict the visible, ultraviolet, and infrared spectra, as well as other properties, of product materials ejected from the muzzle of currently fielded systems. Recent advances in solid propellants has made the management of muzzle signature (flash) a principle issue in weapons development across the calibers. A priori prediction of the electromagnetic spectra of formulations will allow researchers to tailor blends that yield desired signatures and determine spectrographic detection ranges. Quantum chemistry methods at various levels of sophistication have been employed to optimize molecular geometries, compute unscaled harmonic frequencies, and determine the optical spectra of specific gas-phase species. Electronic excitations are being computed using Time Dependent Density Functional Theory (TD-DFT). Calculation of approximate global harmonic frequency scaling factors for specific DFT functionals is also in progress. A full statistical analysis and reliability assessment of computational results is currently underway. Work supported by the ARL, DoD-HPCMP, and USMA.

A comparative analysis of high-throughput platforms for validation of a circulating microRNA signature in diabetic retinopathy.

PubMed

Farr, Ryan J; Januszewski, Andrzej S; Joglekar, Mugdha V; Liang, Helena; McAulley, Annie K; Hewitt, Alex W; Thomas, Helen E; Loudovaris, Tom; Kay, Thomas W H; Jenkins, Alicia; Hardikar, Anandwardhan A

2015-06-02

MicroRNAs are now increasingly recognized as biomarkers of disease progression. Several quantitative real-time PCR (qPCR) platforms have been developed to determine the relative levels of microRNAs in biological fluids. We systematically compared the detection of cellular and circulating microRNA using a standard 96-well platform, a high-content microfluidics platform and two ultra-high content platforms. We used extensive analytical tools to compute inter- and intra-run variability and concordance measured using fidelity scoring, coefficient of variation and cluster analysis. We carried out unprejudiced next generation sequencing to identify a microRNA signature for Diabetic Retinopathy (DR) and systematically assessed the validation of this signature on clinical samples using each of the above four qPCR platforms. The results indicate that sensitivity to measure low copy number microRNAs is inversely related to qPCR reaction volume and that the choice of platform for microRNA biomarker validation should be made based on the abundance of miRNAs of interest.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients.

PubMed

Doñate-Macián, Pau; Gómez, Antonio; Dégano, Irene R; Perálvarez-Marín, Alex

2018-04-06

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico , we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients

PubMed Central

Dégano, Irene R.; Perálvarez-Marín, Alex

2018-01-01

Proteomics aids to the discovery and expansion of protein-protein interaction networks, which are key to understand molecular mechanisms in physiology and physiopathology, but also to infer protein function in a guilt-by-association fashion. In this study we use a systematic protein-protein interaction membrane yeast two-hybrid method to expand the interactome of TRPV2, a cation channel related to nervous system development. After validation of the interactome in silico, we define a TRPV2-interactome signature combining proteomics with the available physio-pathological data in Disgenet to find interactome-disease associations, highlighting nervous system disorders and neoplasms. The TRPV2-interactome signature against available experimental data is capable of discriminating overall risk in glioblastoma multiforme prognosis, progression, recurrence, and chemotherapy resistance. Beyond the impact on glioblastoma physiopathology, this study shows that combining systematic proteomics with in silico methods and available experimental data is key to open new perspectives to define novel biomarkers for diagnosis, prognosis and therapeutics in disease. PMID:29719613

Evaluating Snowmelt Runoff Processes Using Stable Isotopes in a Permafrost Hillslope

NASA Astrophysics Data System (ADS)

Carey, S. K.

2004-05-01

Conceptual understanding of runoff generation in permafrost regions have been derived primarily from hydrometric information, with isotope and hydrochemical data having only limited application in delineating sources and pathways of water. Furthermore, when stable isotope data are used to infer runoff processes, it often provides conflicting results from hydrometric measurements. In a small subarctic alpine catchment within the Wolf Creek Research Basin, Yukon, Canada, experiments were conducted during the melt period of 2002 and 2003 to trace the stable isotopic signature (d18O) of meltwater from a melting snowpack into permafrost soils and laterally to the stream to identify runoff processes and evaluate sources of error for traditional hydrograph separation studies in snowmelt-dominated permafrost basins. Isotopic variability in the snowpack was recorded at 0.1 m depth intervals during the melt period and compared with the meltwater isotopic signature at the snowpack base collected in lysimeters. Throughout the melt period in both years, there was an isotopic enrichment of meltwater as the season progressed. A downslope transect of wells and piezometers were used to evaluate the influence of infiltrating meltwater and thawing ground on the subsurface d18O signature. As melt began, meltwater infiltrated the frozen porous organic layer, leading to liquid water saturation in the unsaturated pore spaces. Water sampled during this initial melt stage show soil water d18O mirroring that of the meltwater signal. As the melt season progressed, frozen soil began to melt, mixing enriched pre-melt soil water with meltwater. This mixing increased the overall value of d18O obtained from the soil, which gradually increased as thaw progressed. At the end of snowmelt, soil water had a d18O value similar to values from the previous fall, suggesting that much of the initial snowmelt water had been flushed from the hillslope. Results from the hillslope scale are compared with two-component hydrograph separations and sources of error are discussed.

Radial Velocity Survey of T Tauri Stars in Taurus-Auriga

NASA Astrophysics Data System (ADS)

Crockett, Christopher; Mahmud, N.; Huerta, M.; Prato, L.; Johns-Krull, C.; Hartigan, P.; Jaffe, D.

2009-01-01

Is the frequency of giant planet companions to young stars similar to that seen around old stars? Is the "brown dwarf desert" a product of how low-mass companion objects form, or of how they evolve? Some models indicate that both giant planets and brown dwarfs should be common at young ages within 3 AU of a primary star, but migration induced by massive disks drive brown dwarfs into the parent stars, leaving behind proportionally more giant planets. Our radial velocity survey of young stars will provide a census of the young giant planet and brown dwarf population in Taurus-Auriga. In this poster we present our progress in quantifying how spurious radial velocity signatures are caused by stellar activity and in developing models to help distinguish between companion induced and spot induced radial velocity variations. Early results stress the importance of complementary observations in both visible light and NIR. We present our technique to determine radial velocities by fitting telluric features and model stellar features to our observed spectra. Finally, we discuss ongoing observations at McDonald Observatory, KPNO, and the IRTF, and several new exoplanet host candidates.

The problem of active SETI: An overview

NASA Astrophysics Data System (ADS)

Musso, Paolo

2012-09-01

In the present paper (originally presented at the First IAA Symposium on Searching for Life Signatures hold at the UNESCO on 22-26 September 2008) I try to summarize the results of all my previous studies on active SETI and its possible dangers for us, also considering some new topics, in order to provide a possibly complete overview of the whole matter. First, I try to evaluate the possible risks of an indirect contact with aliens, from the social, cultural, and religious point of view; then, the possible risks related with receiving information about alien science and technology; finally, the risk that active SETI could increase the probability of a physical contact with hostile aliens. My conclusion is that active SETI is very unlikely to be dangerous for us, but, at present, such a possibility cannot be completely excluded. Surprisingly, it turns out that a very important point to be assessed in order to improve our evaluation of active SETI is the pace of our technological progress. Some suggestions about the policy that international community should adopt towards active SETI are also included.

Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer.

PubMed

Rodríguez, Marta; Silva, Javier; Herrera, Alberto; Herrera, Mercedes; Peña, Cristina; Martín, Paloma; Gil-Calderón, Beatriz; Larriba, María Jesús; Coronado, M Josés; Soldevilla, Beatriz; Turrión, Víctor S; Provencio, Mariano; Sánchez, Antonio; Bonilla, Félix; García-Barberán, Vanesa

2015-12-01

Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.

Raf Kinase Inhibitory Protein (RKIP) as a Metastasis Suppressor: Regulation of Signaling Networks in Cancer

PubMed Central

Yesilkanal, Ali E.; Rosner, Marsha R.

2015-01-01

Cancer is one of the deadliest diseases worldwide, accounting for about 8 million deaths a year. For solid tumors, cancer patients die as a result of the metastatic spread of the tumor to the rest of the body. Therefore, there is a clinical need for understanding the molecular and cellular basis of metastasis, identifying patients whose tumors are more likely to metastasize, and developing effective therapies against metastatic progression. Over the years, Raf kinase inhibitory protein (RKIP) has emerged as a natural suppressor of the metastatic process, constituting a tool for studying metastasis and its clinical outcomes. Here, we review RKIP’s role as a metastasis suppressor and the signaling networks and genes regulated by RKIP in metastatic, triple-negative breast cancer. We also highlight the clinical implications and power of building gene signatures based on RKIP-regulated signaling modules in identifying cancer patients that are at higher risk for metastases. Finally, we highlight the potential of RKIP as a tool for developing new therapeutic strategies in cancer treatment. PMID:25597354

Automated analysis in generic groups

NASA Astrophysics Data System (ADS)

Fagerholm, Edvard

This thesis studies automated methods for analyzing hardness assumptions in generic group models, following ideas of symbolic cryptography. We define a broad class of generic and symbolic group models for different settings---symmetric or asymmetric (leveled) k-linear groups --- and prove ''computational soundness'' theorems for the symbolic models. Based on this result, we formulate a master theorem that relates the hardness of an assumption to solving problems in polynomial algebra. We systematically analyze these problems identifying different classes of assumptions and obtain decidability and undecidability results. Then, we develop automated procedures for verifying the conditions of our master theorems, and thus the validity of hardness assumptions in generic group models. The concrete outcome is an automated tool, the Generic Group Analyzer, which takes as input the statement of an assumption, and outputs either a proof of its generic hardness or shows an algebraic attack against the assumption. Structure-preserving signatures are signature schemes defined over bilinear groups in which messages, public keys and signatures are group elements, and the verification algorithm consists of evaluating ''pairing-product equations''. Recent work on structure-preserving signatures studies optimality of these schemes in terms of the number of group elements needed in the verification key and the signature, and the number of pairing-product equations in the verification algorithm. While the size of keys and signatures is crucial for many applications, another aspect of performance is the time it takes to verify a signature. The most expensive operation during verification is the computation of pairings. However, the concrete number of pairings is not captured by the number of pairing-product equations considered in earlier work. We consider the question of what is the minimal number of pairing computations needed to verify structure-preserving signatures. We build an automated tool to search for structure-preserving signatures matching a template. Through exhaustive search we conjecture lower bounds for the number of pairings required in the Type~II setting and prove our conjecture to be true. Finally, our tool exhibits examples of structure-preserving signatures matching the lower bounds, which proves tightness of our bounds, as well as improves on previously known structure-preserving signature schemes.

Analysis of blood-based gene expression in idiopathic Parkinson disease.

PubMed

Shamir, Ron; Klein, Christine; Amar, David; Vollstedt, Eva-Juliane; Bonin, Michael; Usenovic, Marija; Wong, Yvette C; Maver, Ales; Poths, Sven; Safer, Hershel; Corvol, Jean-Christophe; Lesage, Suzanne; Lavi, Ofer; Deuschl, Günther; Kuhlenbaeumer, Gregor; Pawlack, Heike; Ulitsky, Igor; Kasten, Meike; Riess, Olaf; Brice, Alexis; Peterlin, Borut; Krainc, Dimitri

2017-10-17

To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1 , ATP5A1 , and VDAC3 . We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers. © 2017 American Academy of Neurology.

Optical/Infrared Signatures for Space-Based Remote Sensing

DTIC Science & Technology

2007-11-01

Vanderbilt et al., 1985a, 1985b]. So, first linear polarization was introduced, followed by progress toward a full vector theory of polarization ...radiance profiles taken 30 s apart in a view direction orthogonal to the velocity vector , showing considerable structure due to radiance layers in the...6 Figure 3. The northern polar region and locations of the MSX

Conventional and Non-Conventional Nuclear Material Signatures

NASA Astrophysics Data System (ADS)

Gozani, Tsahi

2009-03-01

The detection and interdiction of concealed special nuclear material (SNM) in all modes of transport is one of the most critical security issues facing the United States and the rest of the world. In principle, detection of nuclear materials is relatively easy because of their unique properties: all of them are radioactive and all emit some characteristic gamma rays. A few emit neutrons as well. These signatures are the basis for passive non-intrusive detection of nuclear materials. The low energy of the radiations necessitates additional means of detection and validation. These are provided by high-energy x-ray radiography and by active inspection based on inducing nuclear reactions in the nuclear materials. Positive confirmation that a nuclear material is present or absent can be provided by interrogation of the inspected object with penetrating probing radiation, such as neutrons and photons. The radiation induces specific reactions in the nuclear material yielding, in turn, penetrating signatures which can be detected outside the inspected object. The "conventional" signatures are first and foremost fission signatures: prompt and delayed neutrons and gamma rays. Their intensity (number per fission) and the fact that they have broad energy (non-discrete, though unique) distributions and certain temporal behaviors are key to their use. The "non- conventional" signatures are not related to the fission process but to the unique nuclear structure of each element or isotope in nature. This can be accessed through the excitation of isotopic nuclear levels (discrete and continuum) by neutron inelastic scattering or gamma resonance fluorescence. Finally there is an atomic signature, namely the high atomic number (Z>74), which obviously includes all the nuclear materials and their possible shielding. The presence of such high-Z elements can be inferred by techniques using high-energy x rays. The conventional signatures have been addressed in another article. Non-conventional signatures and some of their current or potential uses will be discussed here.

Mixed-Fidelity Approach for Design of Low-Boom Supersonic Aircraft

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood; Geiselhart, Karl

2011-01-01

This paper documents a mixed-fidelity approach for the design of low-boom supersonic aircraft with a focus on fuselage shaping.A low-boom configuration that is based on low-fidelity analysis is used as the baseline. The fuselage shape is modified iteratively to obtain a configuration with an equivalent-area distribution derived from computational fluid dynamics analysis that attempts to match a predetermined low-boom target area distribution and also yields a low-boom ground signature. The ground signature of the final configuration is calculated by using a state-of-the-art computational-fluid-dynamics-based boom analysis method that generates accurate midfield pressure distributions for propagation to the ground with ray tracing. The ground signature that is propagated from a midfield pressure distribution has a shaped ramp front, which is similar to the ground signature that is propagated from the computational fluid dynamics equivalent-area distribution. This result supports the validity of low-boom supersonic configuration design by matching a low-boom equivalent-area target, which is easier to accomplish than matching a low-boom midfield pressure target.

Spatial frequency dependence of target signature for infrared performance modeling

NASA Astrophysics Data System (ADS)

Du Bosq, Todd; Olson, Jeffrey

2011-05-01

The standard model used to describe the performance of infrared imagers is the U.S. Army imaging system target acquisition model, based on the targeting task performance metric. The model is characterized by the resolution and sensitivity of the sensor as well as the contrast and task difficulty of the target set. The contrast of the target is defined as a spatial average contrast. The model treats the contrast of the target set as spatially white, or constant, over the bandlimit of the sensor. Previous experiments have shown that this assumption is valid under normal conditions and typical target sets. However, outside of these conditions, the treatment of target signature can become the limiting factor affecting model performance accuracy. This paper examines target signature more carefully. The spatial frequency dependence of the standard U.S. Army RDECOM CERDEC Night Vision 12 and 8 tracked vehicle target sets is described. The results of human perception experiments are modeled and evaluated using both frequency dependent and independent target signature definitions. Finally the function of task difficulty and its relationship to a target set is discussed.

Overview of feasibility study on conducting overflight measurements of shaped sonic boom signatures using RPV's

NASA Technical Reports Server (NTRS)

Maglieri, Domenic J.; Sothcott, Victor E.; Keefer, Thomas N., Jr.; Bobbitt, Percy J.

1992-01-01

Before beginning this presentation, it is appropriate to acknowledge the sincere interest and financial support provided by the NASA LaRC under contract NAS9-17900. An outline of the material to be used in the present paper is given. It begins with a indication of the origin and objectives of the feasibility study. This is followed by a discussion of various simulation methods of establishing the persistence of shaped sonic boom signatures to large distances including the use of recoverable RPV/drones. The desirable features to be sought out in an RPV along with a rationale for the selection of a 'shaped' sonic boom signature will be addressed. Three candidate vehicles are examined as to their suitability with respect to a number of factors, in particular, modifiability. Area distributions and associated sonic boom signatures of the basic and modified Firebee vehicle will also be shown. An indication of the scope of the proposed wind tunnel and flight test programs will be presented including measurement technologies and predicted waveforms. Finally, some remarks will be made summarizing the study and highlighting the key findings.

Mars Rotational and Orbital Dynamics

NASA Image and Video Library

1997-10-14

The Rotation and Orbit Dynamics experiment is based on measuring the Doppler range to Pathfinder using the radio link. Mars rotation about it's pole causes a signature in the data with a daily minimum when the lander is closest to the Earth. Changes in the daily signature reveal information about the planetary interior, through its effect on Mars' precession and nutation. The signature also is sensitive to variations in Mars' rotation rate as the mass of the atmosphere increases and decreases as the polar caps are formed in winter and evaporate in spring. Long term signatures in the range to the lander are caused by asteroids perturbing Mars' orbit. Analysis of these perturbations allows the determination of the masses of asteroids. Sojourner spent 83 days of a planned seven-day mission exploring the Martian terrain, acquiring images, and taking chemical, atmospheric and other measurements. The final data transmission received from Pathfinder was at 10:23 UTC on September 27, 1997. Although mission managers tried to restore full communications during the following five months, the successful mission was terminated on March 10, 1998. http://photojournal.jpl.nasa.gov/catalog/PIA00975

Hyperspectral signature analysis of skin parameters

NASA Astrophysics Data System (ADS)

Vyas, Saurabh; Banerjee, Amit; Garza, Luis; Kang, Sewon; Burlina, Philippe

2013-02-01

The temporal analysis of changes in biological skin parameters, including melanosome concentration, collagen concentration and blood oxygenation, may serve as a valuable tool in diagnosing the progression of malignant skin cancers and in understanding the pathophysiology of cancerous tumors. Quantitative knowledge of these parameters can also be useful in applications such as wound assessment, and point-of-care diagnostics, amongst others. We propose an approach to estimate in vivo skin parameters using a forward computational model based on Kubelka-Munk theory and the Fresnel Equations. We use this model to map the skin parameters to their corresponding hyperspectral signature. We then use machine learning based regression to develop an inverse map from hyperspectral signatures to skin parameters. In particular, we employ support vector machine based regression to estimate the in vivo skin parameters given their corresponding hyperspectral signature. We build on our work from SPIE 2012, and validate our methodology on an in vivo dataset. This dataset consists of 241 signatures collected from in vivo hyperspectral imaging of patients of both genders and Caucasian, Asian and African American ethnicities. In addition, we also extend our methodology past the visible region and through the short-wave infrared region of the electromagnetic spectrum. We find promising results when comparing the estimated skin parameters to the ground truth, demonstrating good agreement with well-established physiological precepts. This methodology can have potential use in non-invasive skin anomaly detection and for developing minimally invasive pre-screening tools.

76 FR 10500 - Nationally Recognized Testing Laboratories Fees

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

... Administration (OSHA), Labor. ACTION: Final rule. SUMMARY: The Occupational Safety and Health Administration... Signature I. Introduction The Occupational Safety and Health Administration (OSHA) is adjusting the approach... DEPARTMENT OF LABOR Occupational Safety and Health Administration 29 CFR Part 1910 [Docket No...

Progress on determining the vapor signature of a buried land mine

NASA Astrophysics Data System (ADS)

George, Vivian; Jenkins, Thomas F.; Leggett, Daniel C.; Cragin, James H.; Phelan, James M.; Oxley, Jimmie C.; Pennington, Judy

1999-08-01

The goal of the DARPA 'Dog's Nose' program is to develop a sensor capable of detecting explosives contained in all buried landmines. In support of the DARPA program, the purpose of the Explosives Fate and Transport experiments is to define in detail the accessible trace chemical signature produced by the explosives contained in buried landmines. We intend to determine the partitioning, composition, and quantity of explosive related chemicals which emanate from different kinds of landmines buried in multiple soil types and exposed to various climatic events. We are also developing a computer model that will enable us to predict the composition and quantity of ERC under a much wider range of environmental conditions than we are able to test experimentally.

Differential transmission of the molecular signature of RBSP3, LIMD1 and CDC25A in basal/ parabasal versus spinous of normal epithelium during head and neck tumorigenesis: A mechanistic study.

PubMed

Sarkar, Shreya; Alam, Neyaz; Mandal, Syam Sundar; Chatterjee, Kabita; Ghosh, Supratim; Roychoudhury, Susanta; Panda, Chinmay Kumar

2018-01-01

Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma.

PubMed

Monteiro, Márcia S; Barros, António S; Pinto, Joana; Carvalho, Márcia; Pires-Luís, Ana S; Henrique, Rui; Jerónimo, Carmen; Bastos, Maria de Lourdes; Gil, Ana M; Guedes de Pinho, Paula

2016-11-18

RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced.

Biological and Clinical Significance of MAD2L1 and BUB1, Genes Frequently Appearing in Expression Signatures for Breast Cancer Prognosis

PubMed Central

Wang, Zhanwei; Katsaros, Dionyssios; Shen, Yi; Fu, Yuanyuan; Canuto, Emilie Marion; Benedetto, Chiara; Lu, Lingeng; Chu, Wen-Ming; Risch, Harvey A.; Yu, Herbert

2015-01-01

To investigate the biologic relevance and clinical implication of genes involved in multiple gene expression signatures for breast cancer prognosis, we identified 16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1. These genes appeared in 5 signatures and were involved in cell-cycle regulation. We analyzed the expression of these genes in relation to tumor features and disease outcomes. In vitro experiments were also performed in two breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration and invasion after knocking down the expression of these genes. High expression of these genes was found to be associated with aggressive tumors and poor disease-free survival of 203 breast cancer patients in our study, and the association with survival was confirmed in an online database consisting of 914 patients. In vitro experiments demonstrated that lowering the expression of these genes by siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our investigation suggests that MAD2L1 and BUB1 may play important roles in breast cancer progression, and measuring the expression of these genes may assist the prediction of breast cancer prognosis. PMID:26287798

Hyperspectral imagery for observing spectral signature change in Aspergillus flavus

NASA Astrophysics Data System (ADS)

DiCrispino, Kevin; Yao, Haibo; Hruska, Zuzana; Brabham, Kori; Lewis, David; Beach, Jim; Brown, Robert L.; Cleveland, Thomas E.

2005-11-01

Aflatoxin contaminated corn is dangerous for domestic animals when used as feed and cause liver cancer when consumed by human beings. Therefore, the ability to detect A. flavus and its toxic metabolite, aflatoxin, is important. The objective of this study is to measure A. flavus growth using hyperspectral technology and develop spectral signatures for A. flavus. Based on the research group's previous experiments using hyperspectral imaging techniques, it has been confirmed that the spectral signature of A. flavus is unique and readily identifiable against any background or surrounding surface and among other fungal strains. This study focused on observing changes in the A. flavus spectral signature over an eight-day growth period. The study used a visible-near-infrared hyperspectral image system for data acquisition. This image system uses focal plane pushbroom scanning for high spatial and high spectral resolution imaging. Procedures previously developed by the research group were used for image calibration and image processing. The results showed that while A. flavus gradually progressed along the experiment timeline, the day-to-day surface reflectance of A. flavus displayed significant difference in discreet regions of the wavelength spectrum. External disturbance due to environmental changes also altered the growth and subsequently changed the reflectance patterns of A. flavus.

Robust transcriptional tumor signatures applicable to both formalin-fixed paraffin-embedded and fresh-frozen samples

PubMed Central

Cheng, Jun; He, Jun; Liu, Huaping; Cai, Hao; Hong, Guini; Zhang, Jiahui; Li, Na; Ao, Lu; Guo, Zheng

2017-01-01

Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable resource for clinical researches. However, FFPE samples are usually considered an unreliable source for gene expression analysis due to the partial RNA degradation. In this study, through comparing gene expression profiles between FFPE samples and paired fresh-frozen (FF) samples for three cancer types, we firstly showed that expression measurements of thousands of genes had at least two-fold change in FFPE samples compared with paired FF samples. Therefore, for a transcriptional signature based on risk scores summarized from the expression levels of the signature genes, the risk score thresholds trained from FFPE (or FF) samples could not be applied to FF (or FFPE) samples. On the other hand, we found that more than 90% of the relative expression orderings (REOs) of gene pairs in the FF samples were maintained in their paired FFPE samples and largely unaffected by the storage time. The result suggested that the REOs of gene pairs were highly robust against partial RNA degradation in FFPE samples. Finally, as a case study, we developed a REOs-based signature to distinguish liver cirrhosis from hepatocellular carcinoma (HCC) using FFPE samples. The signature was validated in four datasets of FFPE samples and eight datasets of FF samples. In conclusion, the valuable FFPE samples can be fully exploited to identify REOs-based diagnostic and prognostic signatures which could be robustly applicable to both FF samples and FFPE samples with degraded RNA. PMID:28036264

A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

PubMed

Hoover, Malachia; Adamian, Yvess; Brown, Mark; Maawy, Ali; Chang, Alexander; Lee, Jacqueline; Gharibi, Armen; Katz, Matthew H; Fleming, Jason; Hoffman, Robert M; Bouvet, Michael; Doebler, Robert; Kelber, Jonathan A

2017-01-24

Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies.

Dynamical Signatures of Structural Connectivity Damage to a Model of the Brain Posed at Criticality.

PubMed

Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

2016-12-01

Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These interareal functional interactions develop in the background of a complex network of axonal connections linking cortical and subcortical neurons, termed the human "structural connectome." Theoretical considerations and experimental evidence support the view that the human brain can be modeled as a system operating at a critical point between ordered (subcritical) and disordered (supercritical) phases. Here, we explore the hypothesis that pathologies resulting from brain injury of different etiologies are related to this model of a critical brain. For this purpose, we investigate how damage to the integrity of the structural connectome impacts on the signatures of critical dynamics. Adopting a hybrid modeling approach combining an empirical weighted network of human structural connections with a conceptual model of critical dynamics, we show that lesions located at highly transited connections progressively displace the model toward the subcritical regime. The topological properties of the nodes and links are of less importance when considered independently of their weight in the network. We observe that damage to midline hubs such as the middle and posterior cingulate cortex is most crucial for the disruption of criticality in the model. However, a similar effect can be achieved by targeting less transited nodes and links whose connection weights add up to an equivalent amount. This implies that brain pathology does not necessarily arise due to insult targeted at well-connected areas and that intersubject variability could obscure lesions located at nonhub regions. Finally, we discuss the predictions of our model in the context of clinical studies of traumatic brain injury and neurodegenerative disorders.

Experimental measurement-device-independent quantum digital signatures.

PubMed

Roberts, G L; Lucamarini, M; Yuan, Z L; Dynes, J F; Comandar, L C; Sharpe, A W; Shields, A J; Curty, M; Puthoor, I V; Andersson, E

2017-10-23

The development of quantum networks will be paramount towards practical and secure telecommunications. These networks will need to sign and distribute information between many parties with information-theoretic security, requiring both quantum digital signatures (QDS) and quantum key distribution (QKD). Here, we introduce and experimentally realise a quantum network architecture, where the nodes are fully connected using a minimum amount of physical links. The central node of the network can act either as a totally untrusted relay, connecting the end users via the recently introduced measurement-device-independent (MDI)-QKD, or as a trusted recipient directly communicating with the end users via QKD. Using this network, we perform a proof-of-principle demonstration of QDS mediated by MDI-QKD. For that, we devised an efficient protocol to distil multiple signatures from the same block of data, thus reducing the statistical fluctuations in the sample and greatly enhancing the final QDS rate in the finite-size scenario.

Medicare program; payment policies under the physician fee schedule, five-year review of work relative value units, clinical laboratory fee schedule: signature on requisition, and other revisions to part B for CY 2012. Final rule with comment period.

PubMed

2011-11-28

This final rule with comment period addresses changes to the physician fee schedule and other Medicare Part B payment policies to ensure that our payment systems are updated to reflect changes in medical practice and the relative value of services. It also addresses, implements or discusses certain statutory provisions including provisions of the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively known as the Affordable Care Act) and the Medicare Improvements for Patients and Providers Act (MIPPA) of 2008. In addition, this final rule with comment period discusses payments for Part B drugs; Clinical Laboratory Fee Schedule: Signature on Requisition; Physician Quality Reporting System; the Electronic Prescribing (eRx) Incentive Program; the Physician Resource-Use Feedback Program and the value modifier; productivity adjustment for ambulatory surgical center payment system and the ambulance, clinical laboratory, and durable medical equipment prosthetics orthotics and supplies (DMEPOS) fee schedules; and other Part B related issues.

Visualization of hyperspectral imagery

NASA Astrophysics Data System (ADS)

Hogervorst, Maarten A.; Bijl, Piet; Toet, Alexander

2007-04-01

We developed four new techniques to visualize hyper spectral image data for man-in-the-loop target detection. The methods respectively: (1) display the subsequent bands as a movie ("movie"), (2) map the data onto three channels and display these as a colour image ("colour"), (3) display the correlation between the pixel signatures and a known target signature ("match") and (4) display the output of a standard anomaly detector ("anomaly"). The movie technique requires no assumptions about the target signature and involves no information loss. The colour technique produces a single image that can be displayed in real-time. A disadvantage of this technique is loss of information. A display of the match between a target signature and pixels and can be interpreted easily and fast, but this technique relies on precise knowledge of the target signature. The anomaly detector signifies pixels with signatures that deviate from the (local) background. We performed a target detection experiment with human observers to determine their relative performance with the four techniques,. The results show that the "match" presentation yields the best performance, followed by "movie" and "anomaly", while performance with the "colour" presentation was the poorest. Each scheme has its advantages and disadvantages and is more or less suited for real-time and post-hoc processing. The rationale is that the final interpretation is best done by a human observer. In contrast to automatic target recognition systems, the interpretation of hyper spectral imagery by the human visual system is robust to noise and image transformations and requires a minimal number of assumptions (about signature of target and background, target shape etc.) When more knowledge about target and background is available this may be used to help the observer interpreting the data (aided target detection).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peek, Gregory W.; Tollefsbol, Trygve O., E-mail: trygve@uab.edu; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL

Human telomerase reverse transcriptase (hTERT) is the catalytic and limiting component of telomerase and also a transcription factor. It is critical to the integrity of the ends of linear chromosomes and to the regulation, extent and rate of cell cycle progression in multicellular eukaryotes. The level of hTERT expression is essential to a wide range of bodily functions and to avoidance of disease conditions, such as cancer, that are mediated in part by aberrant level and regulation of cell cycle proliferation. Value of a gene in regulation depends on its ability to both receive input from multiple sources and transmitmore » signals to multiple effectors. The expression of hTERT and the progression of the cell cycle have been shown to be regulated by an extensive network of gene products and signaling pathways, including the PI3K/Akt and TGF-β pathways. The PI3K inhibitor PX-866 and the competitive estrogen receptor ligand raloxifene have been shown to modify progression of those pathways and, in combination, to decrease proliferation of estrogen receptor positive (ER+) MCF-7 breast cancer cells. We found that combinations of modulators of those pathways decreased not only hTERT transcription but also transcription of additional essential cell cycle regulators such as Cyclin D1. By evaluating known expression profile signatures for TGF-β pathway diversions, we confirmed additional genes such as heparin-binding epidermal growth factor-like growth factor (HB EGF) by which those pathways and their perturbations may also modify cell cycle progression. - Highlights: • PX-866 and raloxifene affect the PI3K/Akt and TGF-β pathways. • PX-866 and raloxifene down-regulate genes up-regulated in cancer. • PX-866 and raloxifene decrease transcription of hTERT and Cyclin D1. • Pathological transcription signatures can identify new defense mechanisms.« less

The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

PubMed Central

2011-01-01

Background Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H+-ATPase (β-F1-ATPase). The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU). Methods The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. Results We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the bioenergetic signature directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the in vitro cell-death responses associated with 3BrP, IA and 5-FU, the in vivo tumor regression activities of these agents were comparable. Conclusions Overall, we suggest that the determination of the bioenergetic signature of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression. PMID:21303518

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

PubMed Central

Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

2012-01-01

Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages. PMID:22485168

Progress at Standard Space Platforms Corporation

NASA Astrophysics Data System (ADS)

Perkins, Frederick W.

1992-08-01

An account is given of a simple program structure with low costs and short schedules for the space R&D community operating outside mission-oriented, government-funded programs. In addition to furnishing launch services into orbit, the program structure furnishes engineering services through its ground station, control room, and 3-year duration 'MMSB' platform. Flights may begin as little as a year after contract signature.

Harnessing Technology to Improve K-12 Education. Discussion Paper 2012-05

ERIC Educational Resources Information Center

Chatterji, Aaron; Jones, Benjamin

2012-01-01

Technological progress has consistently driven remarkable advances in the U.S. economy, yet K-12 education sees little technological change compared to other sectors, even as U.S. K-12 students increasingly lag behind students in other nations. This proposal considers how we can take a signature American strength--innovation--and apply it to K-12…

Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma

PubMed Central

Venkatesan, Arvind M.; Vyas, Rajesh; Gramann, Alec K.; Gujja, Sharvari; Bhatnagar, Sanchita; Gomes, Camilla Borges Ferreira; Xi, Hualin Simon; Lian, Christine G.; Houvras, Yariv; Edwards, Yvonne J. K.; Deng, April; Ceol, Craig J.

2017-01-01

Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers. PMID:29202482

Agricultural crop harvest progress monitoring by fully polarimetric synthetic aperture radar imagery

NASA Astrophysics Data System (ADS)

Yang, Hao; Zhao, Chunjiang; Yang, Guijun; Li, Zengyuan; Chen, Erxue; Yuan, Lin; Yang, Xiaodong; Xu, Xingang

2015-01-01

Dynamic mapping and monitoring of crop harvest on a large spatial scale will provide critical information for the formulation of optimal harvesting strategies. This study evaluates the feasibility of C-band polarimetric synthetic aperture radar (PolSAR) for monitoring the harvesting progress of oilseed rape (Brassica napus L.) fields. Five multitemporal, quad-pol Radarsat-2 images and one optical ZY-1 02C image were acquired over a farmland area in China during the 2013 growing season. Typical polarimetric signatures were obtained relying on polarimetric decomposition methods. Temporal evolutions of these signatures of harvested fields were compared with the ones of unharvested fields in the context of the entire growing cycle. Significant sensitivity was observed between the specific polarimetric parameters and the harvest status of oilseed rape fields. Based on this sensitivity, a new method that integrates two polarimetric features was devised to detect the harvest status of oilseed rape fields using a single image. The validation results are encouraging even for the harvested fields covered with high residues. This research demonstrates the capability of PolSAR remote sensing in crop harvest monitoring, which is a step toward more complex applications of PolSAR data in precision agriculture.

Mass Spectrometric Methodologies for Investigating the Metabolic Signatures of Parkinson's Disease: Current Progress and Future Perspectives.

PubMed

Gill, Emily L; Koelmel, Jeremy P; Yost, Richard A; Okun, Michael S; Vedam-Mai, Vinata; Garrett, Timothy J

2018-03-06

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopaminergic neurons of the substantia nigra as well as degeneration of motor and nonmotor basal ganglia circuitries. Typically known for classical motor deficits (tremor, rigidity, bradykinesia), early stages of the disease are associated with a large nonmotor component (depression, anxiety, apathy, etc.). Currently, there are no definitive biomarkers of PD, and the measurement of dopamine metabolites does not allow for detection of prodromal PD nor does it aid in long-term monitoring of disease progression. Given that PD is increasingly recognized as complex and heterogeneous, involving several neurotransmitters and proteins, it is of importance that we advance interdisciplinary studies to further our knowledge of the molecular and cellular pathways that are affected in PD. This approach will possibly yield useful biomarkers for early diagnosis and may assist in the development of disease-modifying therapies. Here, we discuss preanalytical factors associated with metabolomics studies, summarize current mass spectrometric methodologies used to evaluate the metabolic signature of PD, and provide future perspectives of the rapidly developing field of MS in the context of PD.

Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients.

PubMed

Tan, Tuan Zea; Miow, Qing Hao; Miki, Yoshio; Noda, Tetsuo; Mori, Seiichi; Huang, Ruby Yun-Ju; Thiery, Jean Paul

2014-10-01

Epithelial-mesenchymal transition (EMT) is a reversible and dynamic process hypothesized to be co-opted by carcinoma during invasion and metastasis. Yet, there is still no quantitative measure to assess the interplay between EMT and cancer progression. Here, we derived a method for universal EMT scoring from cancer-specific transcriptomic EMT signatures of ovarian, breast, bladder, lung, colorectal and gastric cancers. We show that EMT scoring exhibits good correlation with previously published, cancer-specific EMT signatures. This universal and quantitative EMT scoring was used to establish an EMT spectrum across various cancers, with good correlation noted between cell lines and tumours. We show correlations between EMT and poorer disease-free survival in ovarian and colorectal, but not breast, carcinomas, despite previous notions. Importantly, we found distinct responses between epithelial- and mesenchymal-like ovarian cancers to therapeutic regimes administered with or without paclitaxel in vivo and demonstrated that mesenchymal-like tumours do not always show resistance to chemotherapy. EMT scoring is thus a promising, versatile tool for the objective and systematic investigation of EMT roles and dynamics in cancer progression, treatment response and survival. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Studies of Westward Electrojets and Field-Aligned Currents in the Magnetotail During Substorms: Implications for Magnetic Field Models

NASA Technical Reports Server (NTRS)

Spence, Harlan E.

1996-01-01

This section outlines those tasks undertaken in the final year that contribute integrally to the overarching project goals. Fast, during the final year, it is important to note that the project benefited greatly with the addition of a Boston University graduate student, Ms. Karen Hirsch. Jointly, we made substantial progress on the development of and improvements to magnetotail magnetic field and plasma models. The ultimate aim of this specific task was to assess critically the utility of such models for mapping low-altitude phenomena into the magnetotail (and vice-versa). The bulk of this effort centered around the finite-width- magnetotail convection model developed by and described by Spence and Kivelson (J. Geophys. Res., 98, 15,487, 1993). This analytic, theoretical model specifies the bulk plasma characteristics of the magnetotail plasma sheet (number density, temperature, pressure) across the full width of the tail from the inner edge of the plasma sheet to lunar distances. Model outputs are specified by boundary conditions of the source particle populations as well as the magnetic and electric field configuration. During the reporting period, we modified this code such that it can be interfaced with the auroral particle precipitation model developed by Dr. Terry Onsager. Together, our models provide a simple analytic specification of the equatorial distribution of fields and plasma along with their low-altitude consequences. Specifically, we have built a simple, yet powerful tool which allows us to indirectly 'map' auroral precipitation signatures (VDIS, inverted-V's, etc.) measured by polar orbiting spacecraft in the ionosphere, to the magnetospheric equatorial plane. The combined models allow us to associate latitudinal gradients measured in the ion energy fluxes at low-altitudes with the large-scale pressure gradients in the equatorial plane. Given this global, quasi-static association, we can then make fairly strong statements regarding the location of discrete features in the context of the global picture. We reported on our initial study at national and international meetings and published the results of our predictions of the low-altitude signatures of the plasma sheet. In addition, the PI was invited to contribute a publication to the so-called 'Great Debate in Space Physics' series that is a feature of EOS. The topic was on the nature of magnetospheric substorms. Specific questions of the when and where a substorm occurs and the connection between the auroral and magnetospheric components were discussed in that paper. This paper therefore was derived exclusively from the research supported by this grant. Attachment: Empirical modeling of the quite time nightside magnetosphere.' 'CRRES observations of particle flux dropout event.' The what, where, when, and why of magnetospheric substorm triggers'. and 'Low altitude signature of the plasma sheet: model prediction of local time dependence'.

Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer.

PubMed

Provenzano, Paolo P; Inman, David R; Eliceiri, Kevin W; Beggs, Hilary E; Keely, Patricia J

2008-11-01

Focal adhesion kinase (FAK) is a central regulator of the focal adhesion, influencing cell proliferation, survival, and migration. Despite evidence demonstrating FAK overexpression in human cancer, its role in tumor initiation and progression is not well understood. Using Cre/LoxP technology to specifically knockout FAK in the mammary epithelium, we showed that FAK is not required for tumor initiation but is required for tumor progression. The mechanistic underpinnings of these results suggested that FAK regulates clinically relevant gene signatures and multiple signaling complexes associated with tumor progression and metastasis, such as Src, ERK, and p130Cas. Furthermore, a systems-level analysis identified FAK as a major regulator of the tumor transcriptome, influencing genes associated with adhesion and growth factor signaling pathways, and their cross talk. Additionally, FAK was shown to down-regulate the expression of clinically relevant proliferation- and metastasis-associated gene signatures, as well as an enriched group of genes associated with the G(2) and G(2)/M phases of the cell cycle. Computational analysis of transcription factor-binding sites within ontology-enriched or clustered gene sets suggested that the differentially expressed proliferation- and metastasis-associated genes in FAK-null cells were regulated through a common set of transcription factors, including p53. Therefore, FAK acts as a primary node in the activated signaling network in transformed motile cells and is a prime candidate for novel therapeutic interventions to treat aggressive human breast cancers.

Gene signatures distinguish stage-specific prostate cancer stem cells isolated from transgenic adenocarcinoma of the mouse prostate lesions and predict the malignancy of human tumors.

PubMed

Mazzoleni, Stefania; Jachetti, Elena; Morosini, Sara; Grioni, Matteo; Piras, Ignazio Stefano; Pala, Mauro; Bulfone, Alessandro; Freschi, Massimo; Bellone, Matteo; Galli, Rossella

2013-09-01

The relevant social and economic impact of prostate adenocarcinoma, one of the leading causes of death in men, urges critical improvements in knowledge of the pathogenesis and cure of this disease. These can also be achieved by implementing in vitro and in vivo preclinical models by taking advantage of prostate cancer stem cells (PCSCs). The best-characterized mouse model of prostate cancer is the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice develop a progressive lesion called prostatic intraepithelial neoplasia that evolves into adenocarcinoma (AD) between 24 and 30 weeks of age. ADs often metastasize to lymph nodes, lung, bones, and kidneys. Eventually, approximately 5% of the mice develop an androgen-independent neuroendocrine adenocarcinoma. Here we report the establishment of long-term self-renewing PCSC lines from the different stages of TRAMP progression by application of the neurosphere assay. Stage-specific prostate cell lines were endowed with the critical features expected from malignant bona fide cancer stem cells, namely, self-renewal, multipotency, and tumorigenicity. Notably, transcriptome analysis of stage-specific PCSCs resulted in the generation of well-defined, meaningful gene signatures, which identify distinct stages of human tumor progression. As such, TRAMP-derived PCSCs represent a novel and valuable preclinical model for elucidating the pathogenetic mechanisms leading to prostate adenocarcinoma and for the identification of molecular mediators to be pursued as therapeutic targets.

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

PubMed Central

Chang, Ping-Ying; Liao, Yu-Ping; Wang, Hui-Chen; Chen, Yu-Chih; Huang, Rui-Lan; Wang, Yu-Chi; Yuan, Chiou-Chung; Lai, Hung-Cheng

2017-01-01

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. PMID:28881822

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression.

PubMed

Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E; Joshi, Virendra; Salomon, Carlos

2017-03-07

Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a 'fingerprint' of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

A model independent search for new physics in final states containing leptons at the DO experiment

NASA Astrophysics Data System (ADS)

Piper, Joel M.

The standard model is known to be the low energy limit of a more general theory. Several consequences of the standard model point to a strong probability of new physics becoming experimentally visible in high energy collisions of a few TeV, resulting in high momentum objects. The specific signatures of these collisions are topics of much debate. Rather than choosing a specific signature, this analysis broadly searches the data, preferring breadth over sensitivity. In searching for new physics, several different approaches are used. These include the comparison of data with standard model background expectation in overall number of events, comparisons of distributions of many kinematic variables, and finally comparisons on the tails of distributions that sum the momenta of the objects in an event. With 1.07 fb-1 at the DO experiment, we find no evidence of physics beyond the standard model. Several discrepancies from the standard model were found, but none of these provide a compelling case for new physics.

Color-octet scalars of N = 2 supersymmetry at the LHC

NASA Astrophysics Data System (ADS)

Choi, S. Y.; Drees, M.; Kalinowski, J.; Kim, J. M.; Popenda, E.; Zerwas, P. M.

2009-02-01

The color gauge hyper-multiplet in N = 2 supersymmetry consists of the usual N = 1 gauge vector/gaugino super-multiplet, joined with a novel gaugino/scalar super-multiplet. Large cross sections are predicted for the production of pairs of the color-octet scalars σ [sgluons] at the LHC: gg, qqbar → σσ*. Single σ production is possible at one-loop level, but the gg → σ amplitude vanishes in the limit of degenerate L and R squarks. When kinematically allowed, σ decays predominantly into two gluinos, whose cascade decays give rise to a burst of eight or more jets together with four LSP's as signature for σ pair events at the LHC. σ can also decay into a squark-antisquark pair at tree level. At one-loop level σ decays into gluons or a ttbar pair are predicted, generating exciting resonance signatures in the final states. The corresponding partial widths are very roughly comparable to that for three body final states mediated by one virtual squark at tree level.

Signatures of mountain building: Detrital zircon U/Pb ages from northeast Tibet

USGS Publications Warehouse

Lease, Richard O.; Burbank, Douglas W.; Gehrels, George E.; Wang, Zhicai; Yuan, Daoyang

2007-01-01

Although detrital zircon has proven to be a powerful tool for determining provenance, past work has focused primarily on delimiting regional source terranes. Here we explore the limits of spatial resolution and stratigraphic sensitivity of detrital zircon in ascertaining provenance, and we demonstrate its ability to detect source changes for terranes separated by only a few tens of kilometers. For such an analysis to succeed for a given mountain, discrete intrarange source terranes must have unique U/Pb zircon age signatures and sediments eroded from the range must have well-defined depositional ages. Here we use ∼1400 single-grain U/Pb zircon ages from northeastern Tibet to identify and analyze an area that satisfies these conditions. This analysis shows that the edges of intermontane basins are stratigraphically sensitive to discrete, punctuated changes in local source terranes. By tracking eroding rock units chronologically through the stratigraphic record, this sensitivity permits the detection of the differential rock uplift and progressive erosion that began ca. 8 Ma in the Laji Shan, a 10-25-km-wide range in northeastern Tibet with a unique U/Pb age signature.

Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology.

PubMed

Dunkel, Andreas; Steinhaus, Martin; Kotthoff, Matthias; Nowak, Bettina; Krautwurst, Dietmar; Schieberle, Peter; Hofmann, Thomas

2014-07-07

The biocatalytic production of flavor naturals that determine chemosensory percepts of foods and beverages is an ever challenging target for academic and industrial research. Advances in chemical trace analysis and post-genomic progress at the chemistry-biology interface revealed odor qualities of nature's chemosensory entities to be defined by odorant-induced olfactory receptor activity patterns. Beyond traditional views, this review and meta-analysis now shows characteristic ratios of only about 3 to 40 genuine key odorants for each food, from a group of about 230 out of circa 10 000 food volatiles. This suggests the foodborn stimulus space has co-evolved with, and roughly match our circa 400 olfactory receptors as best natural agonists. This perspective gives insight into nature's chemical signatures of smell, provides the chemical odor codes of more than 220 food samples, and beyond addresses industrial implications for producing recombinants that fully reconstruct the natural odor signatures for use in flavors and fragrances, fully immersive interactive virtual environments, or humanoid bioelectronic noses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Handwriting changes due to aging and Parkinson's syndrome.

PubMed

Walton, J

1997-08-22

Wills signed by elderly people are often contested on the grounds the the signature is different from their earlier specimen signatures. Neurological disease, which can affect handwriting, is very common and progressive amongst elderly people. Handwriting change due to old age and neurological disease is poorly understood. To better understand this subject, we carried out a large methodical study based on almost 200 handwriting specimens of Parkinson patients and age-matched controls. Interestingly, our findings indicate that some of the handwriting changes which occur in these populations tend to resemble forgery indicia although upon close inspection they are distinguishable from them. Thus, document examiners are urged to exercise caution in assessing purported forgeries on wills and other documents signed of written during older age or a writer suffering from neurological disease.

Multidimensional Raman spectroscopic signatures as a tool for forensic identification of body fluid traces: a review.

PubMed

Sikirzhytski, Vitali; Sikirzhytskaya, Aliaksandra; Lednev, Igor K

2011-11-01

The analysis of body fluid traces during forensic investigations is a critical step in determining the key details of a crime. Several confirmatory and presumptive biochemical tests are currently utilized. However, these tests are all destructive, and no single method can be used to analyze all body fluids. This review outlines recent progress in the development of a novel universal approach for the nondestructive, confirmatory identification of body fluid traces using Raman spectroscopy. The method is based on the use of multidimensional spectroscopic signatures of body fluids and accounts for the intrinsic heterogeneity of dry traces and donor variation. The results presented here demonstrate that Raman spectroscopy has potential for identifying traces of semen, blood, saliva, sweat, and vaginal fluid with high confidence.

Asteroid and comet surfaces

NASA Technical Reports Server (NTRS)

Mcfadden, Lucy-Ann

1988-01-01

Photometric and spectrophotometric studies of asteroids and comets are in progress to address questions about the mineralogical relationship between asteroids near the 3:1 Kirkwood gap and ordinary chondrite meteorites and between cometary nuclei and the surface of asteroids. Progress was made on a method to convert the measured excess UV flux in the spectrum of 2201 Oljato to column abundance of OH and CN. Spectral reflectance measurements of large asteroids near the 3:1 Kirkwood gap, which is expected to be the source of ordinary chondrite meteorites, were briefly examined and show no spectral signatures that are characteristic of ordinary chondrite meteorite powders measured in the lab.

A Real-Time Infrared Ultra-Spectral Signature Classification Method via Spatial Pyramid Matching

PubMed Central

Mei, Xiaoguang; Ma, Yong; Li, Chang; Fan, Fan; Huang, Jun; Ma, Jiayi

2015-01-01

The state-of-the-art ultra-spectral sensor technology brings new hope for high precision applications due to its high spectral resolution. However, it also comes with new challenges, such as the high data dimension and noise problems. In this paper, we propose a real-time method for infrared ultra-spectral signature classification via spatial pyramid matching (SPM), which includes two aspects. First, we introduce an infrared ultra-spectral signature similarity measure method via SPM, which is the foundation of the matching-based classification method. Second, we propose the classification method with reference spectral libraries, which utilizes the SPM-based similarity for the real-time infrared ultra-spectral signature classification with robustness performance. Specifically, instead of matching with each spectrum in the spectral library, our method is based on feature matching, which includes a feature library-generating phase. We calculate the SPM-based similarity between the feature of the spectrum and that of each spectrum of the reference feature library, then take the class index of the corresponding spectrum having the maximum similarity as the final result. Experimental comparisons on two publicly-available datasets demonstrate that the proposed method effectively improves the real-time classification performance and robustness to noise. PMID:26205263

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model.

PubMed

Huang, Yanqi; He, Lan; Dong, Di; Yang, Caiyun; Liang, Cuishan; Chen, Xin; Ma, Zelan; Huang, Xiaomei; Yao, Su; Liang, Changhong; Tian, Jie; Liu, Zaiyi

2018-02-01

To develop and validate a radiomics prediction model for individualized prediction of perineural invasion (PNI) in colorectal cancer (CRC). After computed tomography (CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort (346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen (CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation (separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram. The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index (c-index): 0.817; 95% confidence interval (95% CI): 0.811-0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination (c-index: 0.803; 95% CI: 0.794-0.812). Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

PubMed Central

Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

2013-01-01

Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies. PMID:23704896

Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.

PubMed

Colak, Dilek; Nofal, Asmaa; Albakheet, Albandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; Al-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Inan, Mehmet S; Kaya, Namik; Park, Ben H; Bin Amer, Suad M

2013-01-01

Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.

A Predictive Metabolic Signature for the Transition From Gestational Diabetes Mellitus to Type 2 Diabetes.

PubMed

Allalou, Amina; Nalla, Amarnadh; Prentice, Kacey J; Liu, Ying; Zhang, Ming; Dai, Feihan F; Ning, Xian; Osborne, Lucy R; Cox, Brian J; Gunderson, Erica P; Wheeler, Michael B

2016-09-01

Gestational diabetes mellitus (GDM) affects 3-14% of pregnancies, with 20-50% of these women progressing to type 2 diabetes (T2D) within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1,035 women with GDM pregnancy were enrolled at 6-9 weeks postpartum (baseline) and were screened for T2D annually for 2 years. Of 1,010 women without T2D at baseline, 113 progressed to T2D within 2 years. T2D developed in another 17 women between 2 and 4 years. A nested case-control design used 122 incident case patients matched to non-case patients by age, prepregnancy BMI, and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, which is far superior to measuring fasting plasma glucose levels alone. The American Diabetes Association recommends T2D screening in the early postpartum period via oral glucose tolerance testing after GDM, which is a time-consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting blood sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions. © 2016 by the American Diabetes Association.

A Predictive Metabolic Signature for the Transition From Gestational Diabetes Mellitus to Type 2 Diabetes

PubMed Central

Allalou, Amina; Nalla, Amarnadh; Prentice, Kacey J.; Liu, Ying; Zhang, Ming; Dai, Feihan F.; Ning, Xian; Osborne, Lucy R.; Cox, Brian J.

2016-01-01

Gestational diabetes mellitus (GDM) affects 3–14% of pregnancies, with 20–50% of these women progressing to type 2 diabetes (T2D) within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1,035 women with GDM pregnancy were enrolled at 6–9 weeks postpartum (baseline) and were screened for T2D annually for 2 years. Of 1,010 women without T2D at baseline, 113 progressed to T2D within 2 years. T2D developed in another 17 women between 2 and 4 years. A nested case-control design used 122 incident case patients matched to non–case patients by age, prepregnancy BMI, and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, which is far superior to measuring fasting plasma glucose levels alone. The American Diabetes Association recommends T2D screening in the early postpartum period via oral glucose tolerance testing after GDM, which is a time-consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting blood sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions. PMID:27338739

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2013-08-01

This project is to use cutting-edge technologies to characterize novel RSR genes and their functions in tumor suppression; identify gene signature...and membrane proteins associated with defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for...screening and validation of drugs that target RSR-defect cells. The progress of our third year research is described below. BODY The tasks

Development of techniques for producing static strata maps and development of photointerpretive methods based on multitemporal LANDSAT data

NASA Technical Reports Server (NTRS)

Colwell, R. N. (Principal Investigator); Hay, C. M.; Thomas, R. W.; Benson, A. S.

1977-01-01

Progress in the evaluation of the static stratification procedure and the development of alternative photointerpretive techniques to the present LACIE procedure for the identification of training fields is reported. Statistically significant signature controlling variables were defined for use in refining the stratification procedure. A subset of the 1973-74 Kansas LACIE segments for wheat was analyzed.

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes.

PubMed

Mehdi, Ahmed M; Hamilton-Williams, Emma E; Cristino, Alexandre; Ziegler, Anette; Bonifacio, Ezio; Le Cao, Kim-Anh; Harris, Mark; Thomas, Ranjeny

2018-03-08

Autoimmune-mediated destruction of pancreatic islet β cells results in type 1 diabetes (T1D). Serum islet autoantibodies usually develop in genetically susceptible individuals in early childhood before T1D onset, with multiple islet autoantibodies predicting diabetes development. However, most at-risk children remain islet-antibody negative, and no test currently identifies those likely to seroconvert. We sought a genomic signature predicting seroconversion risk by integrating longitudinal peripheral blood gene expression profiles collected in high-risk children included in the BABYDIET and DIPP cohorts, of whom 50 seroconverted. Subjects were followed for 10 years to determine time of seroconversion. Any cohort effect and the time of seroconversion were corrected to uncover genes differentially expressed (DE) in seroconverting children. Gene expression signatures associated with seroconversion were evident during the first year of life, with 67 DE genes identified in seroconverting children relative to those remaining antibody negative. These genes contribute to T cell-, DC-, and B cell-related immune responses. Near-birth expression of ADCY9, PTCH1, MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5, along with HLA risk score predicted seroconversion (AUC 0.85). The ubiquitin-proteasome pathway linked DE genes and T1D susceptibility genes. Therefore, a gene expression signature in infancy predicts risk of seroconversion. Ubiquitination may play a mechanistic role in diabetes progression.

A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes

PubMed Central

Mehdi, Ahmed M.; Hamilton-Williams, Emma E.; Cristino, Alexandre; Ziegler, Anette; Harris, Mark

2018-01-01

Autoimmune-mediated destruction of pancreatic islet β cells results in type 1 diabetes (T1D). Serum islet autoantibodies usually develop in genetically susceptible individuals in early childhood before T1D onset, with multiple islet autoantibodies predicting diabetes development. However, most at-risk children remain islet-antibody negative, and no test currently identifies those likely to seroconvert. We sought a genomic signature predicting seroconversion risk by integrating longitudinal peripheral blood gene expression profiles collected in high-risk children included in the BABYDIET and DIPP cohorts, of whom 50 seroconverted. Subjects were followed for 10 years to determine time of seroconversion. Any cohort effect and the time of seroconversion were corrected to uncover genes differentially expressed (DE) in seroconverting children. Gene expression signatures associated with seroconversion were evident during the first year of life, with 67 DE genes identified in seroconverting children relative to those remaining antibody negative. These genes contribute to T cell–, DC-, and B cell–related immune responses. Near-birth expression of ADCY9, PTCH1, MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5, along with HLA risk score predicted seroconversion (AUC 0.85). The ubiquitin-proteasome pathway linked DE genes and T1D susceptibility genes. Therefore, a gene expression signature in infancy predicts risk of seroconversion. Ubiquitination may play a mechanistic role in diabetes progression. PMID:29515040

Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.

PubMed

Nsengimana, Jérémie; Laye, Jon; Filia, Anastasia; Walker, Christy; Jewell, Rosalyn; Van den Oord, Joost J; Wolter, Pascal; Patel, Poulam; Sucker, Antje; Schadendorf, Dirk; Jönsson, Göran B; Bishop, D Timothy; Newton-Bishop, Julia

2015-05-10

Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3 x 10(-4)), Breslow thickness (P=5 x 10(-10)), ulceration (P=9.x10-8) and mitotic rate (P=3 x 10(-7)), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.

High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice

PubMed Central

Kahle, M.; Schäfer, A.; Seelig, A.; Schultheiß, J.; Wu, M.; Aichler, M.; Leonhardt, J.; Rathkolb, B.; Rozman, J.; Sarioglu, H.; Hauck, S.M.; Ueffing, M.; Wolf, E.; Kastenmueller, G.; Adamski, J.; Walch, A.; Hrabé de Angelis, M.; Neschen, S.

2014-01-01

Objective Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. Methods We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. Results Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. Conclusions We assume HF-induced modifications in membrane lipid- and protein-signatures prior to and during changes in hepatic insulin action in liver alter membrane properties – in particular those of mitochondria which are highly abundant in hepatocytes. In turn, a progressive decrease in the abundance of mitochondrial membrane proteins throughout HF-exposure likely impacts on mitochondrial energy metabolism, substrate exchange across mitochondrial membranes, contributes to oxidative stress, mitochondrial damage, and the development of insulin resistance in liver. PMID:25685688

Injury and Disability: Identification and Reduction

DTIC Science & Technology

2009-09-01

Biomechanics Branch September 2009 Final Report for October 2005 to August 2009 DESTRUCTION NOTICE – Destroy by any method that will prevent...Division Biomechanics Branch Wright-Patterson AFB OH 45433 Approved for public release, distribution unlimited. NOTICE AND SIGNATURE PAGE...Chief Biomechanics Branch Biosciences and Protection Division Human Effectiveness Directorate 711 th

Nucleolar Reorganization Upon Site-Specific Double-Strand Break Induction.

PubMed

Franek, Michal; Kovaříková, Alena; Bártová, Eva; Kozubek, Stanislav

2016-11-01

DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I- PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I- PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, γH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I- PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps.

Molecular Gas Feeding the Circumnuclear Disk of the Galactic Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Pei-Ying; Koch, Patrick M.; Ho, Paul T. P.

The interaction between a supermassive black hole (SMBH) and the surrounding material is of primary importance in modern astrophysics. The detection of the molecular 2 pc circumnuclear disk (CND) immediately around the Milky Way SMBH, SgrA*, provides a unique opportunity to study SMBH accretion at subparsec scales. Our new wide-field CS( J = 2 − 1) map toward the Galactic center (GC) reveals multiple dense molecular streamers that originated from the ambient clouds 20 pc further out, and that are connected to the central 2 pc of the CND. These dense gas streamers appear to carry gas directly toward themore » nuclear region and might be captured by the central potential. Our phase-plot analysis indicates that these streamers show a signature of rotation and inward radial motion with progressively higher velocities as the gas approaches the CND and finally ends up corotating with the CND. Our results might suggest a possible mechanism of gas feeding the CND from 20 pc around 2 pc in the GC. In this paper, we discuss the morphology and the kinematics of these streamers. As the nearest observable Galactic nucleus, this feeding process may have implications for understanding the processes in extragalactic nuclei.« less

An unmetasomatized source for the Malaitan alnoeite (Solomon Islands): Petrogenesis involving zone refining, megacryst fractionation, and assimilation of oceanic lithosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neal, C.R.; Davidson, J.P.

The Malaitan alnoite contains a rich and varied megacryst suite of unprecedented compositional range. The authors have undertaken trace element and isotope modeling in order to formulate a petrogenetic scheme which links the host alnoeite to its entrained megacrysts. This requires that a proto-alnoeite magma is the product of zone refining initiated by diapiric upwelling (where the initial melt passes through 200 times its volume of mantle). Isotopic evidence indicates the source of the proto-alnoeite contains a time-integrated LREE-depleted signature. Impingement upon the rigid lithosphere halts or dramatically slows the upward progress of the mantle diapir. At this point, themore » magma cools and megacryst fractionation begins with augites crystallizing first, followed by subcalcic diopsides and finally phlogopites. Garnet probably crystallizes over the entire range of clinopyroxene fractionation. Estimated proportions of fractionating phases are 30% augite, 24.5% subcalcic diopside, 27% garnet, 12.9% phlogopite, 5% bronzite, 0.5% ilmenite, and 0.1% zircon. As this proto-alnoeite magma crystallizes, it assimilates a subducted component of seawater-altered basalt which underplates the Ontong Java Plateau. This is witnessed in the isotopic composition of the megacrysts and alnoeite.« less

Molecular Gas Feeding the Circumnuclear Disk of the Galactic Center

NASA Astrophysics Data System (ADS)

Hsieh, Pei-Ying; Koch, Patrick M.; Ho, Paul T. P.; Kim, Woong-Tae; Tang, Ya-Wen; Wang, Hsiang-Hsu; Yen, Hsi-Wei; Hwang, Chorng-Yuan

2017-09-01

The interaction between a supermassive black hole (SMBH) and the surrounding material is of primary importance in modern astrophysics. The detection of the molecular 2 pc circumnuclear disk (CND) immediately around the Milky Way SMBH, SgrA*, provides a unique opportunity to study SMBH accretion at subparsec scales. Our new wide-field CS(J = 2 - 1) map toward the Galactic center (GC) reveals multiple dense molecular streamers that originated from the ambient clouds 20 pc further out, and that are connected to the central 2 pc of the CND. These dense gas streamers appear to carry gas directly toward the nuclear region and might be captured by the central potential. Our phase-plot analysis indicates that these streamers show a signature of rotation and inward radial motion with progressively higher velocities as the gas approaches the CND and finally ends up corotating with the CND. Our results might suggest a possible mechanism of gas feeding the CND from 20 pc around 2 pc in the GC. In this paper, we discuss the morphology and the kinematics of these streamers. As the nearest observable Galactic nucleus, this feeding process may have implications for understanding the processes in extragalactic nuclei.

Acoustic investigation of the aperture dynamics of an elastic membrane closing an overpressurized cylindrical cavity

NASA Astrophysics Data System (ADS)

Sánchez, Claudia; Vidal, Valérie; Melo, Francisco

2015-08-01

We report an experimental study of the acoustic signal produced by the rupture of an elastic membrane that initially closes a cylindrical overpressurized cavity. This configuration has been recently used as an experimental model system for the investigation of the acoustic emission from the bursting of elongated gas bubbles rising in a conduit. Here, we investigate the effect of the membrane rupture dynamics on the acoustic signal produced by the pressure release by changing the initial tension of the membrane. The initial overpressure in the cavity is fixed at a value such that the system remains in the linear acoustic regime. For large initial membrane deformation, the rupture time τ rup is small compared to the wave propagation time in the cavity and the pressure wave inside the conduit can be fully captured by the linear theory. For low membrane tension, a hole is pierced in the membrane but its rupture does not occur. For intermediate deformation, finally, the rupture progresses in two steps: first the membrane opens slowly; then, after reaching a critical size, the rupture accelerates. A transversal wave is excited along the membrane surface. The characteristic signature of each opening dynamics on the acoustic emission is described.

Pseudoscalar portal dark matter and new signatures of vector-like fermions

DOE PAGES

Fan, JiJi; Koushiappas, Savvas M.; Landsberg, Greg

2016-01-19

Fermionic dark matter interacting with the Standard Model sector through a pseudoscalar portal could evade the direct detection constraints while preserving a WIMP miracle. Here, we study the LHC constraints on the pseudoscalar production in simplified models with the pseudoscalar either dominantly coupled to b quarks ormore » $${{\\tau}}$$ leptons and explore their implications for the GeV excesses in gamma ray observations. We also investigate models with new vector-like fermions that could realize the simplfied models of pseudoscalar portal dark matter. Furthermore, these models yield new decay channels and signatures of vector-like fermions, for instance, bbb; b$${{\\tau}}$$ $${{\\tau}}$$, and $${{\\tau}}$$ $${{\\tau}}$$ $${{\\tau}}$$ resonances. Some of the signatures have already been strongly constrained by the existing LHC searches and the parameter space fitting the gamma ray excess is further restricted. Conversely, the pure $${{\\tau}}$$-rich final state is only weakly constrained so far due to the small electroweak production rate.« less

A study of the limitations of linear theory methods as applied to sonic boom calculations

NASA Technical Reports Server (NTRS)

Darden, Christine M.

1990-01-01

Current sonic boom minimization theories have been reviewed to emphasize the capabilities and flexibilities of the methods. Flexibility is important because it is necessary for the designer to meet optimized area constraints while reducing the impact on vehicle aerodynamic performance. Preliminary comparisons of sonic booms predicted for two Mach 3 concepts illustrate the benefits of shaping. Finally, for very simple bodies of revolution, sonic boom predictions were made using two methods - a modified linear theory method and a nonlinear method - for signature shapes which were both farfield N-waves and midfield waves. Preliminary analysis on these simple bodies verified that current modified linear theory prediction methods become inadequate for predicting midfield signatures for Mach numbers above 3. The importance of impulse is sonic boom disturbance and the importance of three-dimensional effects which could not be simulated with the bodies of revolution will determine the validity of current modified linear theory methods in predicting midfield signatures at lower Mach numbers.

Quantification of temperature effect on impedance monitoring via PZT interface for prestressed tendon anchorage

NASA Astrophysics Data System (ADS)

Huynh, Thanh-Canh; Kim, Jeong-Tae

2017-12-01

In this study, the quantification of temperature effect on impedance monitoring via a PZT interface for prestressed tendon-anchorage is presented. Firstly, a PZT interface-based impedance monitoring technique is selected to monitor impedance signatures by predetermining sensitive frequency bands. An analytical model is designed to represent coupled dynamic responses of the PZT interface-tendon anchorage system. Secondly, experiments on a lab-scaled tendon anchorage are described. Impedance signatures are measured via the PZT interface for a series of temperature and prestress-force changes. Thirdly, temperature effects on measured impedance responses of the tendon anchorage are estimated by quantifying relative changes in impedance features (such as RMSD and CCD indices) induced by temperature variation and prestress-force change. Finally, finite element analyses are conducted to investigate the mechanism of temperature variation and prestress-loss effects on the impedance responses of prestressed tendon anchorage. Temperature effects on impedance monitoring are filtered by effective frequency shift-based algorithm for distinguishing prestress-loss effects on impedance signatures.

Signatures of the Adler–Bell–Jackiw chiral anomaly in a Weyl fermion semimetal

DOE PAGES

Zhang, Cheng-Long; Xu, Su-Yang; Belopolski, Ilya; ...

2016-02-25

Weyl semimetals provide the realization of Weyl fermions in solid-state physics. Among all the physical phenomena that are enabled by Weyl semimetals, the chiral anomaly is the most unusual one. Here, we report signatures of the chiral anomaly in the magneto-transport measurements on the first Weyl semimetal TaAs. We show negative magnetoresistance under parallel electric and magnetic fields, that is, unlike most metals whose resistivity increases under an external magnetic field, we observe that our high mobility TaAs samples become more conductive as a magnetic field is applied along the direction of the current for certain ranges of the fieldmore » strength. We present systematically detailed data and careful analyses, which allow us to exclude other possible origins of the observed negative magnetoresistance. Finally, our transport data, corroborated by photoemission measurements, first-principles calculations and theoretical analyses, collectively demonstrate signatures of the Weyl fermion chiral anomaly in the magneto-transport of TaAs.« less

Monotop signature from a fermionic top partner

NASA Astrophysics Data System (ADS)

Gonçalves, Dorival; Kong, Kyoungchul; Sakurai, Kazuki; Takeuchi, Michihisa

2018-01-01

We investigate monotop signatures arising from phenomenological models of fermionic top partners, which are degenerate in mass and decay into a bosonic dark matter candidate, either spin 0 or spin 1. Such a model provides a monotop signature as a smoking gun, while conventional searches with t t ¯ + missing transverse momentum are limited. Two such scenarios, (i) a phenomenological third generation extradimensional model with excited top and electroweak sectors, and (ii) a model where only a top partner and a dark matter particle are added to the standard model, are studied in the degenerate mass regime. We find that in the case of extra dimension a number of different processes give rise to effectively the same monotop final state, and a great gain can be obtained in the sensitivity for this channel. We show that the monotop search can explore top-partner masses up to 630 and 300 GeV for the third generation extradimensional model and the minimal fermionic top-partner model, respectively, at the high luminosity LHC.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chng, Brenda; Mann, Robert; Department of Physics, University of Waterloo 200 University Avenue West, Waterloo, Ontario N2L 3G1

We construct new solutions of the vacuum Einstein field equations in four dimensions via a solution-generating method utilizing the SL(2,R) symmetry of the reduced Lagrangian. We apply the method to an accelerating version of the Zipoy-Voorhees solution and generate new solutions which we interpret to be the accelerating versions of the Zipoy-Voorhees generalization of the Taub-NUT solution (with Lorentzian signature) and the Zipoy-Voorhees generalization of the Eguchi-Hanson solitons (with Euclidean signature). As an intermediary in the solution-generating process we obtain charged versions of the accelerated Zipoy-Voorhees-like families of solutions. Finally we present the accelerating version of the Taub-NUT solution andmore » discuss its properties.« less

Toward Monitoring Parkinson's Through Analysis of Static Handwriting Samples: A Quantitative Analytical Framework.

PubMed

Zhi, Naiqian; Jaeger, Beverly Kris; Gouldstone, Andrew; Sipahi, Rifat; Frank, Samuel

2017-03-01

Detection of changes in micrographia as a manifestation of symptomatic progression or therapeutic response in Parkinson's disease (PD) is challenging as such changes can be subtle. A computerized toolkit based on quantitative analysis of handwriting samples would be valuable as it could supplement and support clinical assessments, help monitor micrographia, and link it to PD. Such a toolkit would be especially useful if it could detect subtle yet relevant changes in handwriting morphology, thus enhancing resolution of the detection procedure. This would be made possible by developing a set of metrics sensitive enough to detect and discern micrographia with specificity. Several metrics that are sensitive to the characteristics of micrographia were developed, with minimal sensitivity to confounding handwriting artifacts. These metrics capture character size-reduction, ink utilization, and pixel density within a writing sample from left to right. They are used here to "score" handwritten signatures of 12 different individuals corresponding to healthy and symptomatic PD conditions, and sample control signatures that had been artificially reduced in size for comparison purposes. Moreover, metric analyses of samples from ten of the 12 individuals for which clinical diagnosis time is known show considerable informative variations when applied to static signature samples obtained before and after diagnosis. In particular, a measure called pixel density variation showed statistically significant differences ( ) between two comparison groups of remote signature recordings: earlier versus recent, based on independent and paired t-test analyses on a total of 40 signature samples. The quantitative framework developed here has the potential to be used in future controlled experiments to study micrographia and links to PD from various aspects, including monitoring and assessment of applied interventions and treatments. The inherent value in this methodology is further enhanced by its reliance solely on static signatures, not requiring dynamic sampling with specialized equipment.

A Roadmap to Fundamental Physics from LISA EMRI Observations

NASA Astrophysics Data System (ADS)

Sopuerta, Carlos F.

2010-09-01

The Laser Interferometer Space Antenna is a future space-based gravitational-wave observatory (a joint mission between the European Space Agency and the US National Aeronautics and Space Administration) that is expected to be launched during the next decade. It will operate in the low-frequency gravitational-wave band, probably the richest part of the gravitational-wave spectrum in terms of science potential, where we find: massive black hole mergers as the outcome of galaxy collisions; many galactic compact binaries; the capture and subsequent inspiral of a stellar compact object into a massive black hole; and gravitational-wave signatures from early universe physical processes connected to high-energy physics and physics not yet fully understood. In this article we focus on the third type of source, the so-called extreme-mass-ratio inspirals, a high precision tool for gravitational wave astronomy that can be used, among other things, to advance in our understanding of fundamental physics questions like the nature and structure of black holes and the details of the gravitational interaction in regimes not yet proven by other experiments/observatories. Here, we give an account of some of the progress made in the development of tools to exploit the future LISA EMRI observations, we discuss what scientific questions we can try to answer from this information and, finally, we discuss the main theoretical challenges that we face in order to develop all the necessary tools to maximize the scientific outcome and some avenues that can be followed to make progress in the near future.

Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Scott

2010-07-31

“Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

Endogenous Versus Exogenous Shocks in Complex Networks: An Empirical Test Using Book Sale Rankings

NASA Astrophysics Data System (ADS)

Sornette, D.; Deschâtres, F.; Gilbert, T.; Ageon, Y.

2004-11-01

We study the precursory and recovery signatures accompanying shocks in complex networks, that we test on a unique database of the Amazon.com ranking of book sales. We find clear distinguishing signatures classifying two types of sales peaks. Exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. These results are rationalized quantitatively by a simple model of epidemic propagation of interactions with long memory within a network of acquaintances. The observed relaxation of sales implies that the sales dynamics is dominated by cascades rather than by the direct effects of news or advertisements, indicating that the social network is close to critical.

Endogenous versus exogenous shocks in complex networks: an empirical test using book sale rankings.

PubMed

Sornette, D; Deschâtres, F; Gilbert, T; Ageon, Y

2004-11-26

We study the precursory and recovery signatures accompanying shocks in complex networks, that we test on a unique database of the Amazon.com ranking of book sales. We find clear distinguishing signatures classifying two types of sales peaks. Exogenous peaks occur abruptly and are followed by a power law relaxation, while endogenous peaks occur after a progressively accelerating power law growth followed by an approximately symmetrical power law relaxation which is slower than for exogenous peaks. These results are rationalized quantitatively by a simple model of epidemic propagation of interactions with long memory within a network of acquaintances. The observed relaxation of sales implies that the sales dynamics is dominated by cascades rather than by the direct effects of news or advertisements, indicating that the social network is close to critical.

Endogenous versus Exogenous Origins of Crises

NASA Astrophysics Data System (ADS)

Sornette, Didier

Are large biological extinctions such as the Cretaceous/Tertiary KT boundary due to a meteorite, extreme volcanic activity or self-organized critical extinction cascades? Are commercial successes due to a progressive reputation cascade or the result of a well orchestrated advertisement? Determining the chain of causality for Xevents in complex systems requires disentangling interwoven exogenous and endogenous contributions with either no clear signature or too many signatures. Here, I review several efforts carried out with collaborators which suggest a general strategy for understanding the organizations of several complex systems under the dual effect of endogenous and exogenous fluctuations. The studied examples are: internet download shocks, book sale shocks, social shocks, financial volatility shocks, and financial crashes. Simple models are offered to quantitatively relate the endogenous organization to the exogenous response of the system. Suggestions for applications of these ideas to many other systems are offered.

Primordial Black Holes: Observational characteristics of the final evaporation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ukwatta, T. N.; Stump, D. R.; Linnemann, J. T.

For many early universe theories predict the creation of Primordial Black Holes (PBHs). PBHs could have masses ranging from the Planck mass to 105 solar masses or higher depending on the size of the universe at formation. A Black Hole (BH) has a Hawking temperature which is inversely proportional to its mass. Hence a sufficiently small BH will quasi-thermally radiate particles at an ever-increasing rate as emission lowers its mass and raises its temperature. Moreover, the final moments of this evaporation phase should be explosive and its description is dependent on the particle physics model. In this work we investigatemore » the final few seconds of BH evaporation, using the Standard Model and incorporating the most recent Large Hadron Collider (LHC) results, and provide a new parameterization for the instantaneous emission spectrum. We calculate for the first time energy-dependent PBH burst light curves in the GeV/TeV energy range. Moreover, we explore PBH burst search methods and potential observational PBH burst signatures. We have found a unique signature in the PBH burst light curves that may be detectable by GeV/TeV gamma-ray observatories such as the High Altitude Water Cerenkov (HAWC) observatory. Finally, the implications of beyond the Standard Model theories on the PBH burst observational characteristics are also discussed, including potential sensitivity of the instantaneous photon detection rate to a squark threshold in the 5–10 TeV range.« less

Primordial Black Holes: Observational characteristics of the final evaporation

DOE PAGES

Ukwatta, T. N.; Stump, D. R.; Linnemann, J. T.; ...

2016-07-01

For many early universe theories predict the creation of Primordial Black Holes (PBHs). PBHs could have masses ranging from the Planck mass to 105 solar masses or higher depending on the size of the universe at formation. A Black Hole (BH) has a Hawking temperature which is inversely proportional to its mass. Hence a sufficiently small BH will quasi-thermally radiate particles at an ever-increasing rate as emission lowers its mass and raises its temperature. Moreover, the final moments of this evaporation phase should be explosive and its description is dependent on the particle physics model. In this work we investigatemore » the final few seconds of BH evaporation, using the Standard Model and incorporating the most recent Large Hadron Collider (LHC) results, and provide a new parameterization for the instantaneous emission spectrum. We calculate for the first time energy-dependent PBH burst light curves in the GeV/TeV energy range. Moreover, we explore PBH burst search methods and potential observational PBH burst signatures. We have found a unique signature in the PBH burst light curves that may be detectable by GeV/TeV gamma-ray observatories such as the High Altitude Water Cerenkov (HAWC) observatory. Finally, the implications of beyond the Standard Model theories on the PBH burst observational characteristics are also discussed, including potential sensitivity of the instantaneous photon detection rate to a squark threshold in the 5–10 TeV range.« less

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression

PubMed Central

Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E.; Joshi, Virendra; Salomon, Carlos

2017-01-01

Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (∼150-1000 nm) and exosomes (∼40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a fingerprint of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression. PMID:27999198

RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer

PubMed Central

Kulkarni, Madhura; Tan, Tuan Zea; Syed Sulaiman, Nurfarhanah Bte; Lamar, John M.; Bansal, Prashali; Cui, Jianzhou; Qiao, Yiting; Ito, Yoshiaki

2018-01-01

Hippo pathway target, YAP has emerged as an important player in solid tumor progression. Here, we identify RUNX1 and RUNX3 as novel negative regulators of oncogenic function of YAP in the context of breast cancer. RUNX proteins are one of the first transcription factors identified to interact with YAP. RUNX1 or RUNX3 expression abrogates YAP-mediated pro-tumorigenic properties of mammary epithelial cell lines in an interaction dependent manner. RUNX1 and RUNX3 inhibit YAP-mediated migration and stem-ness properties of mammary epithelial cell lines by co-regulating YAP-mediated gene expression. Analysis of whole genome expression profiles of breast cancer samples revealed significant co-relation between YAP–RUNX1/RUNX3 expression levels and survival outcomes of breast cancer patients. High RUNX1/RUNX3 expression proved protective towards YAP-dependent patient survival outcomes. High YAP in breast cancer patients’ expression profiles co-related with EMT and stem-ness gene signature enrichment. High RUNX1/RUNX3 expression along with high YAP reflected lower enrichment of EMT and stem-ness signatures. This antagonistic activity of RUNX1 and RUNX3 towards oncogenic function of YAP identified in mammary epithelial cells as well as in breast cancer expression profiles gives a novel mechanistic insight into oncogene–tumor suppressor interplay in the context of breast cancer progression. The novel interplay between YAP, RUNX1 and RUNX3 and its significance in breast cancer progression can serve as a prognostic tool to predict cancer recurrence. PMID:29581836

Second-harmonic generation and fluorescence lifetime imaging microscopy through a rodent mammary imaging window

NASA Astrophysics Data System (ADS)

Young, Pamela A.; Nazir, Muhammad; Szulczewski, Michael J.; Keely, Patricia J.; Eliceiri, Kevin W.

2012-03-01

Tumor-Associated Collagen Signatures (TACS) have been identified that manifest in specific ways during breast tumor progression and that correspond to patient outcome. There are also compelling metabolic changes associated with carcinoma invasion and progression. We have characterized the difference in the autofluorescent properties of metabolic co-factors, NADH and FAD, between normal and carcinoma breast cell lines. Also, we have shown in vitro that increased collagen density alters metabolic genes which are associated with glycolysis and leads to a more invasive phenotype. Establishing the relationship between collagen density, cellular metabolism, and metastasis in physiologically relevant cancer models is crucial for developing cancer therapies. To study cellular metabolism with respect to collagen density in vivo, we use multiphoton fluorescence excitation microscopy (MPM) in conjunction with a rodent mammary imaging window implanted in defined mouse cancer models. These models are ideal for the study of collagen changes in vivo, allowing determination of corresponding metabolic changes in breast cancer invasion and progression. To measure cellular metabolism, we collect fluorescence lifetime (FLIM) signatures of NADH and FAD, which are known to change based on the microenvironment of the cells. Additionally, MPM systems are capable of collecting second harmonic generation (SHG) signals which are a nonlinear optical property of collagen. Therefore, MPM, SHG, and FLIM are powerful tools with great potential for characterizing key features of breast carcinoma in vivo. Below we present the current efforts of our collaborative group to develop intravital approaches based on these imaging techniques to look at defined mouse mammary models.

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

PubMed Central

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

In vivo SILAC-based proteomics reveals phosphoproteome changes during mouse skin carcinogenesis.

PubMed

Zanivan, Sara; Meves, Alexander; Behrendt, Kristina; Schoof, Erwin M; Neilson, Lisa J; Cox, Jürgen; Tang, Hao R; Kalna, Gabriela; van Ree, Janine H; van Deursen, Jan M; Trempus, Carol S; Machesky, Laura M; Linding, Rune; Wickström, Sara A; Fässler, Reinhard; Mann, Matthias

2013-02-21

Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Issues and approaches for electronic document approval and transmittal using digital signatures and text authentication: Prototype documentation

NASA Astrophysics Data System (ADS)

Boling, M. E.

1989-09-01

Prototypes were assembled pursuant to recommendations made in report K/DSRD-96, Issues and Approaches for Electronic Document Approval and Transmittal Using Digital Signatures and Text Authentication, and to examine and discover the possibilities for integrating available hardware and software to provide cost effective systems for digital signatures and text authentication. These prototypes show that on a LAN, a multitasking, windowed, mouse/keyboard menu-driven interface can be assembled to provide easy and quick access to bit-mapped images of documents, electronic forms and electronic mail messages with a means to sign, encrypt, deliver, receive or retrieve and authenticate text and signatures. In addition they show that some of this same software may be used in a classified environment using host to terminal transactions to accomplish these same operations. Finally, a prototype was developed demonstrating that binary files may be signed electronically and sent by point to point communication and over ARPANET to remote locations where the authenticity of the code and signature may be verified. Related studies on the subject of electronic signatures and text authentication using public key encryption were done within the Department of Energy. These studies include timing studies of public key encryption software and hardware and testing of experimental user-generated host resident software for public key encryption. This software used commercially available command-line source code. These studies are responsive to an initiative within the Office of the Secretary of Defense (OSD) for the protection of unclassified but sensitive data. It is notable that these related studies are all built around the same commercially available public key encryption products from the private sector and that the software selection was made independently by each study group.

Observational Signatures Of Agn Feedback Across Cosmic Time

NASA Astrophysics Data System (ADS)

Wylezalek, Dominika

2017-06-01

While many compelling models of AGN feedback exist, there is no clear data-driven picture of how winds are launched, how they propagate through the galaxy and what impact they have on the galactic gas. Recent work suggests that AGN luminosity plays an important role. The following described projects focus on understanding the power, reach and impact of feedback processes exerted by AGN of different power. I first describe recent efforts in our group of relating feedback signatures in powerful quasars to the specific star formation rate in their host galaxies, where our results are consistent with the AGN having a `negative' impact through feedback on the galaxies' star formation history. Feedback signatures seem to be best observable in gas-rich galaxies where the coupling of the AGN-driven wind to the gas is strongest, in agreement with recent simulations. But how and where does this quenching happen? Is it accomplished through the mechanical action of jets or through nuclear winds driven by radiation pressure? Finally, I show that AGN signatures and AGN-driven winds can be easily hidden and not be apparent in the integrated spectrum of a galaxy hosting a low/intermediate-luminosity AGN. Using data from the new SDSS-IV MaNGA survey, we have developed a new AGN selection algorithm tailored to IFU data and we are uncovering a much more nuanced picture of AGN activity allowing us to discover AGN signatures at large distances from the galaxy center. This implies that large IFU surveys, such as the SDSS-IV MaNGA survey, might uncover many previously unknown AGN and feedback signatures related to them. Outflows and feedback from low- and intermediate-luminosity AGN might have been underestimated in the past but can potentially significantly contribute to the AGN/host-galaxy self-regulation.

Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial.

PubMed

Siano, Marco; Espeli, Vittoria; Mach, Nicolas; Bossi, Paolo; Licitra, Lisa; Ghielmini, Michele; Frattini, Milo; Canevari, Silvana; De Cecco, Loris

2018-07-01

Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy. Whole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy. Cluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E-13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877). Despite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advanced Cancer Genomics Institute: Genetic Signatures and Therapeutic Targets in Cancer Progression

DTIC Science & Technology

2014-02-01

Roswell Park Cancer Institute Division, Buffalo, NY 14263 REPORT DATE: February 2014 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army...PERFORMING ORGANIZATION REPORT NUMBER Roswell Park Cancer Institute Elm and Carlton Streets Buffalo, NY 14263 9. SPONSORING...prostatectomy material to isolate RNA and DNA from AD- and CR-CaP cases. Roswell Park already has produced a 5- slide tumor microarray containing 722 CaP

Targeting Estrogen-Induced COX-2 Activity in Lymphangioleiomyomatosis (LAM)

DTIC Science & Technology

2013-10-01

significant benefit in slowing LAM progression. The well-known side - effect and toxicity profile of these drugs make them attractive candidates for...well-known side - effect and toxicity profile of these drugs make them attractive candidates for long-term therapy in LAM patients. It is also possible...induced prostaglandin biosynthesis signature in TSC2- deficient cells in vitro and in vivo To examine the possible effects of estradiol on metabolic

Elucidation of the genetic and epigenetic landscape alterations in RNA binding proteins in glioblastoma

PubMed Central

Mahalingam, Kulandaivelu; Somasundaram, Kumaravel

2017-01-01

RNA binding proteins (RBPs) have been implicated in cancer development. An integrated bioinformatics analysis of RBPs (n = 1756) in various datasets (n = 11) revealed several genetic and epigenetically altered events among RBPs in glioblastoma (GBM). We identified 13 mutated and 472 differentially regulated RBPs in GBM samples. Mutations in AHNAK predicted poor prognosis. Copy number variation (CNV), DNA methylation and miRNA targeting contributed to RBP differential regulation. Two sets of differentially regulated RBPs that may be implicated in initial astrocytic transformation and glioma progression were identified. We have also identified a four RBP (NOL3, SUCLG1, HERC5 and AFF3) signature, having a unique expression pattern in glioma stem-like cells (GSCs), to be an independent poor prognostic indicator in GBM. RBP risk score derived from the signature also stratified GBM into low-risk and high-risk groups with significant survival difference. Silencing NOL3, SUCLG1 and HERC5 inhibited GSC maintenance. Gene set enrichment analysis of differentially regulated genes between high-risk and low-risk underscored the importance of inflammation, EMT and hypoxia in high-risk GBM. Thus, we provide a comprehensive overview of genetic and epigenetic regulation of RBPs in glioma development and progression. PMID:28035070

Concise Review: Current Status and Future Directions on Research Related to Nonalcoholic Fatty Liver Disease.

PubMed

Wruck, Wasco; Graffmann, Nina; Kawala, Marie-Ann; Adjaye, James

2017-01-01

Considered a feature of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), is associated with insulin resistance, type 2 diabetes, obesity and drug toxicity. Its prevalence is estimated at about 30% in western countries mainly due to sedentary life styles and high fat diets. Genome-wide association studies have identified polymorphisms in several genes, for example, PNPLA3, and TM6SF2 which confer susceptibility to NAFLD. Here, we review recent findings in the NAFLD field with a particular focus on published transcriptomics datasets which we subject to a meta-analysis. We reveal a common gene signature correlating with the progression of the disease from steatosis and steatohepatitis and reveal that lipogenic and cholesterol metabolic pathways are main actors in this signature. We propose the use of disease-in-a-dish models based on hepatocyte-like cells derived from patient-specific induced pluripotent stem cells (iPSC). These will enable investigations into the contribution of genetic background in the progression from NALFD to non-alcoholic steatohepatitis. Furthermore, an iPSC-based approach should aid in the elucidation of the function of new biomarkers, thus enabling better diagnostic tests and validation of potential drug targets. Stem Cells 2017;35:89-96. © 2016 AlphaMed Press.

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

PubMed Central

Bermudo, R; Abia, D; Mozos, A; García-Cruz, E; Alcaraz, A; Ortiz, Á R; Thomson, T M; Fernández, P L

2011-01-01

Introduction: Currently, final diagnosis of prostate cancer (PCa) is based on histopathological analysis of needle biopsies, but this process often bears uncertainties due to small sample size, tumour focality and pathologist's subjective assessment. Methods: Prostate cancer diagnostic signatures were generated by applying linear discriminant analysis to microarray and real-time RT–PCR (qRT–PCR) data from normal and tumoural prostate tissue samples. Additionally, after removal of biopsy tissues, material washed off from transrectal biopsy needles was used for molecular profiling and discriminant analysis. Results: Linear discriminant analysis applied to microarray data for a set of 318 genes differentially expressed between non-tumoural and tumoural prostate samples produced 26 gene signatures, which classified the 84 samples used with 100% accuracy. To identify signatures potentially useful for the diagnosis of prostate biopsies, surplus material washed off from routine biopsy needles from 53 patients was used to generate qRT–PCR data for a subset of 11 genes. This analysis identified a six-gene signature that correctly assigned the biopsies as benign or tumoural in 92.6% of the cases, with 88.8% sensitivity and 96.1% specificity. Conclusion: Surplus material from prostate needle biopsies can be used for minimal-size gene signature analysis for sensitive and accurate discrimination between non-tumoural and tumoural prostates, without interference with current diagnostic procedures. This approach could be a useful adjunct to current procedures in PCa diagnosis. PMID:22009027

The nanomechanical signature of liver cancer tissues and its molecular origin

NASA Astrophysics Data System (ADS)

Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

2015-07-01

Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC. Electronic supplementary information (ESI) available: Detailed experimental procedures and supplementary figures. See DOI: 10.1039/c5nr02192h

Superboom Caustic Analysis and Measurement Program (SCAMP) Final Report

NASA Technical Reports Server (NTRS)

Page, Juliet; Plotkin, Ken; Hobbs, Chris; Sparrow, Vic; Salamone, Joe; Cowart, Robbie; Elmer, Kevin; Welge, H. Robert; Ladd, John; Maglieri, Domenic;

The Effect of Lithospheric Discontinuities on the Composition of Lavas From the Northern Galápagos Platform Extension

NASA Astrophysics Data System (ADS)

Schlitzer, W.; Harpp, K. S.; Mittelstaedt, E. L.; Kurz, M. D.; Geist, D.

2011-12-01

The platform supporting the Galápagos Archipelago extends ~50 km NW toward the Galápagos Spreading Center (GSC) into the Northern Galapagos Volcanic Province (NGVP), where it underlies Pinta, Marchena, and Genovesa Islands. Approximately 45 km north of Pinta is the southern termination of a ~100-km long transform fault, at 90o50'W. The seafloor surrounding the NGVP was surveyed and dredged during the 2010 MV1007 and 2001 DRIFT04 cruises. All the large volcanoes, including the islands, have elongate bathymetric footprints with extensive submarine ridges. Lavas from this small region (<150 km in diameter) exhibit isotopic and trace element signatures that span the compositional range of the entire Galápagos Archipelago. Pinta and its submarine extension have the most enriched signatures, whereas at the eastern end of the platform extension, Genovesa is indistinguishable from normal MORB. Samples dredged around Pinta and Marchena have intermediate compositions. In contrast, lavas from the adjacent transform fault are more depleted than those from Genovesa and anywhere along the GSC for hundreds of km in both directions. Lavas from this region exhibit a range of 3He/4He (6.5-9.5 Ra), significantly lower than the high 3He/4He signature of material erupted by the plume-rich western Galápagos shield volcanoes (>25 Ra). Whereas the compositions of lavas erupted on the Nazca Plate in the NGVP require 3 or more distinct mantle endmembers to explain their compositions, our data indicate that the platform extension region only requires components previously described for the Galápagos Islands. In addition, Sm/Yb decreases abruptly along an E-W transect from Pinta to Genovesa. Gibson and Geist (2010) concluded that Sm/Yb ratios reflect variations in surface wave velocities (Villagomez et al., 2007), enabling them to predict lithospheric thickness. We apply the relationship defined by Gibson and Geist to map lithospheric thickness across our study area. Our results suggest that the lithosphere (and thus minimum melt generation depth) gets progressively shallower from Pinta to Genovesa; this phenomenon may explain unexpected Holocene volcanism in the NGVP. The wide range in Sm/Yb further suggests a complex lithospheric structure underlying the platform extension, which we propose reflects formation of the adjacent GSC transform fault within the last ~3 Ma, possibly through a series of ridge jumps as suggested by modeling of new magnetic data. We propose a model in which heterogeneous plume material with enriched and depleted components (Ito and Mahoney, 2005) is migrating toward the GSC along the base of the lithosphere, having previously lost its primordial helium signature during deep melting near the western shield volcanoes. As the material crosses the complex lithospheric thickness variations in the NGVP, melt generation becomes progressively shallower. The enriched compositions at Pinta thus result from limited, deep melting of enriched compositions owing to a thick lithospheric cap. East of Pinta, the plume melts more extensively and to shallower depths, producing progressively depleted signatures toward Genovesa.

Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

PubMed Central

Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

2013-01-01

The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer.

PubMed

Korsunsky, Ilya; Parameswaran, Janaki; Shapira, Iuliana; Lovecchio, John; Menzin, Andrew; Whyte, Jill; Dos Santos, Lisa; Liang, Sharon; Bhuiya, Tawfiqul; Keogh, Mary; Khalili, Houman; Pond, Cassandra; Liew, Anthony; Shih, Andrew; Gregersen, Peter K; Lee, Annette T

2017-10-01

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Predicting Zoonotic Risk of Influenza A Viruses from Host Tropism Protein Signature Using Random Forest

PubMed Central

Eng, Christine L. P.; Tong, Joo Chuan; Tan, Tin Wee

2017-01-01

Influenza A viruses remain a significant health problem, especially when a novel subtype emerges from the avian population to cause severe outbreaks in humans. Zoonotic viruses arise from the animal population as a result of mutations and reassortments, giving rise to novel strains with the capability to evade the host species barrier and cause human infections. Despite progress in understanding interspecies transmission of influenza viruses, we are no closer to predicting zoonotic strains that can lead to an outbreak. We have previously discovered distinct host tropism protein signatures of avian, human and zoonotic influenza strains obtained from host tropism predictions on individual protein sequences. Here, we apply machine learning approaches on the signatures to build a computational model capable of predicting zoonotic strains. The zoonotic strain prediction model can classify avian, human or zoonotic strains with high accuracy, as well as providing an estimated zoonotic risk. This would therefore allow us to quickly determine if an influenza virus strain has the potential to be zoonotic using only protein sequences. The swift identification of potential zoonotic strains in the animal population using the zoonotic strain prediction model could provide us with an early indication of an imminent influenza outbreak. PMID:28587080

Predicting Zoonotic Risk of Influenza A Viruses from Host Tropism Protein Signature Using Random Forest.

PubMed

Eng, Christine L P; Tong, Joo Chuan; Tan, Tin Wee

2017-05-25

Influenza A viruses remain a significant health problem, especially when a novel subtype emerges from the avian population to cause severe outbreaks in humans. Zoonotic viruses arise from the animal population as a result of mutations and reassortments, giving rise to novel strains with the capability to evade the host species barrier and cause human infections. Despite progress in understanding interspecies transmission of influenza viruses, we are no closer to predicting zoonotic strains that can lead to an outbreak. We have previously discovered distinct host tropism protein signatures of avian, human and zoonotic influenza strains obtained from host tropism predictions on individual protein sequences. Here, we apply machine learning approaches on the signatures to build a computational model capable of predicting zoonotic strains. The zoonotic strain prediction model can classify avian, human or zoonotic strains with high accuracy, as well as providing an estimated zoonotic risk. This would therefore allow us to quickly determine if an influenza virus strain has the potential to be zoonotic using only protein sequences. The swift identification of potential zoonotic strains in the animal population using the zoonotic strain prediction model could provide us with an early indication of an imminent influenza outbreak.

Neural Signatures of Stimulus Features in Visual Working Memory—A Spatiotemporal Approach

PubMed Central

Jackson, Margaret C.; Klein, Christoph; Mohr, Harald; Shapiro, Kimron L.; Linden, David E. J.

2010-01-01

We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal “what/where” segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams. PMID:19429863

Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus*

PubMed Central

Cha, Jeeyeon; Burnum-Johnson, Kristin E.; Bartos, Amanda; Li, Yingju; Baker, Erin S.; Tilton, Susan C.; Webb-Robertson, Bobbie-Jo M.; Piehowski, Paul D.; Monroe, Matthew E.; Jegga, Anil G.; Murata, Shigeo; Hirota, Yasushi; Dey, Sudhansu K.

2015-01-01

Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. PMID:25931120

The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes.

PubMed

O'Dwyer, David N; Norman, Katy C; Xia, Meng; Huang, Yong; Gurczynski, Stephen J; Ashley, Shanna L; White, Eric S; Flaherty, Kevin R; Martinez, Fernando J; Murray, Susan; Noth, Imre; Arnold, Kelly B; Moore, Bethany B

2017-04-25

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than 1100 proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology.

Biodynamic digital holography of chemoresistance in a pre-clinical trial of canine B-cell lymphoma.

PubMed

Choi, Honggu; Li, Zhe; Sun, Hao; Merrill, Dan; Turek, John; Childress, Michael; Nolte, David

2018-05-01

Biodynamic digital holography was used to obtain phenotypic profiles of canine non-Hodgkin B-cell lymphoma biopsies treated with standard-of-care chemotherapy. Biodynamic signatures from the living 3D tissues were extracted using fluctuation spectroscopy from intracellular Doppler light scattering in response to the molecular mechanisms of action of therapeutic drugs that modify a range of internal cellular motions. The standard-of-care to treat B-cell lymphoma in both humans and dogs is a combination CHOP therapy that consists of doxorubicin, prednisolone, cyclophosphamide and vincristine. The proportion of dogs experiencing durable cancer remission following CHOP chemotherapy was 68%, with 13 out of 19 dogs responding favorably to therapy and 6 dogs failing to have progression-free survival times greater than 100 days. Biodynamic signatures were found that correlate with inferior survival times, and biomarker selection was optimized to identify specific Doppler signatures related to chemoresistance. A machine learning classifier was constructed based on feature vector correlations and linear separability in high-dimensional feature space. Hold-out validation predicted patient response to therapy with 84% accuracy. These results point to the potential for biodynamic profiling to contribute to personalized medicine by aiding the selection of chemotherapy for cancer patients.

Using Oxygen and Carbon Isotopic Signatures in Order to Infer Climatic and Dietary Information in Roman Edessa, Greece

NASA Astrophysics Data System (ADS)

Michael, Dimitra-Ermioni; Dotsika, Elissavet

2017-12-01

Even though many isotopic studies have been conducted on ancient populations from Greece for the purpose of dietary reconstruction; mostly through carbon and nitrogen isotopic signals of bone collagen, less attention has been given to the utility of apatite signatures (oxygen and carbon) as dietary and palaeoenvironmental tools. Moreover, until recently the isotopic signal of tooth enamel for both the purposes of environmental and dietary reconstructions has been rarely assessed in ancient Greek societies. Therefore, the present study aims to provide with novel isotopic information regarding Edessa; a town in Northern Greece, during the Roman period. The current study primarily aims to explore the possible differentiation between the present climatic conditions in Edessa in relation to those occurring at the Roman period. Secondly, this study aims to reveal the significant utility of enamel isotopic signatures (carbon and oxygen) in palaeoenvironmental and palaeodietary studies regarding ancient human remains. The isotopic analyses have been conducted at the Stable Isotope and Radiocarbon Unit of INN, NCSR “Demokritos”. The population of Roman Edessa (2nd-4th c. AD) consists of 22 individuals, providing with 19 bone samples and 16 enamel ones. The mean enamel oxygen value is at -7.7 ±1.1 %0, the bone apatite mean oxygen value at -9.2 ±1.9 %0, and finally the mean carbon enamel value is at -11.7 ±1.2 %0. Oxygen values probably indicate that Edessa had a cooler climate during the Roman times in relation to present conditions, even though more research should be carried out in order to be more certain. In addition, the possible existence of non-local individuals has been revealed through the oxygen teeth enamel-bone apatite spacing. Finally, the carbon enamel signature has pointed out possible differentiations between the adult and the juvenile diet. Based on Edessa’s findings, the stated study strongly encourages the enamel oxygen and carbon isotopic signals as palaeoclimatological and palaeodietary tools respectively.

Characterization and Validation of Transiting Planets in the Kepler and TESS Pipelines

NASA Astrophysics Data System (ADS)

Twicken, Joseph; Brownston, Lee; Catanzarite, Joseph; Clarke, Bruce; Cote, Miles; Girouard, Forrest; Li, Jie; McCauliff, Sean; Seader, Shawn; Tenenbaum, Peter; Wohler, Bill; Jenkins, Jon Michael; Batalha, Natalie; Bryson, Steve; Burke, Christopher; Caldwell, Douglas

2015-08-01

Light curves for Kepler targets are searched for transiting planet signatures in the Transiting Planet Search (TPS) component of the Science Operations Center (SOC) Processing Pipeline. Targets for which the detection threshold is exceeded are subsequently processed in the Data Validation (DV) Pipeline component. The primary functions of DV are to (1) characterize planets identified in the transiting planet search, (2) search for additional transiting planet signatures in light curves after modeled transit signatures have been removed, and (3) perform a comprehensive suite of diagnostic tests to aid in discrimination between true transiting planets and false positive detections. DV output products include extensive reports by target, one-page report summaries by planet candidate, and tabulated planet model fit and diagnostic test results. The DV products are employed by humans and automated systems to vet planet candidates identified in the pipeline. The final revision of the Kepler SOC codebase (9.3) was released in March 2015. It will be utilized to reprocess the complete Q1-Q17 data set later this year. At the same time, the SOC Pipeline codebase is being ported to support the Transiting Exoplanet Survey Satellite (TESS) Mission. TESS is expected to launch in 2017 and survey the entire sky for transiting exoplanets over a period of two years. We describe the final revision of the Kepler Data Validation component with emphasis on the diagnostic tests and reports. This revision also serves as the DV baseline for TESS. The diagnostic tests exploit the flux (i.e., light curve), centroid and pixel time series associated with each target to facilitate the determination of the true origin of each purported transiting planet signature. Candidate planet detections and DV products for Kepler are delivered to the Exoplanet Archive at the NASA Exoplanet Science Institute (NExScI). The Exoplanet Archive is located at exoplanetarchive.ipac.caltech.edu. Funding for the Kepler and TESS Missions has been provided by the NASA Science Mission Directorate.

33 CFR 325.2 - Processing of applications.

Code of Federal Regulations, 2011 CFR

2011-07-01

... advised in writing of the reason(s) for denial. If the final decision is to issue the permit and a... on the permit application is the signature on the letter notifying the applicant of the denial of the... request and, where applicable, upon the payment of administrative fees. This list will be distributed to...

33 CFR 325.2 - Processing of applications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... advised in writing of the reason(s) for denial. If the final decision is to issue the permit and a... on the permit application is the signature on the letter notifying the applicant of the denial of the... request and, where applicable, upon the payment of administrative fees. This list will be distributed to...

Final Technical Report: PV Fault Detection Tool.

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Bruce Hardison; Jones, Christian Birk

The PV Fault Detection Tool project plans to demonstrate that the FDT can (a) detect catastrophic and degradation faults and (b) identify the type of fault. This will be accomplished by collecting fault signatures using different instruments and integrating this information to establish a logical controller for detecting, diagnosing and classifying each fault.

Multifractality of sectoral price indices: Hurst signature analysis of Cantillon effects in disequilibrium factor markets

NASA Astrophysics Data System (ADS)

Mulligan, Robert F.

2014-06-01

This paper presents Hurst exponent signatures from time series of aggregate price indices for the US over the 1975-2011 time period. Though all highly aggregated, these indices include both broad measures of consumer and producer prices. The constellation of prices evolves as a complex system throughout processes of production and distribution, culminating in the final delivery of output to consumers. Massive feedback characterizes this system, where the demand for consumable output determines the demand for the inputs used to produce it, and supply scarcities for the necessary inputs in turn determine the supply of the final product. Prices in both factor and output markets are jointly determined by interdependent supply and demand conditions. Fractal examination of the interplay among market prices would be of interest regardless, but added interest arises from the consideration of how these markets respond to external shocks over the business cycle, particularly monetary expansion. Because the initial impact of monetary injection is localized in specific sectors, the way the impact on prices diffuses throughout the economy is of special interest.

Comparative expression profiling in grape (Vitis vinifera) berries derived from frequency analysis of ESTs and MPSS signatures.

PubMed

Iandolino, Alberto; Nobuta, Kan; da Silva, Francisco Goes; Cook, Douglas R; Meyers, Blake C

2008-05-12

Vitis vinifera (V. vinifera) is the primary grape species cultivated for wine production, with an industry valued annually in the billions of dollars worldwide. In order to sustain and increase grape production, it is necessary to understand the genetic makeup of grape species. Here we performed mRNA profiling using Massively Parallel Signature Sequencing (MPSS) and combined it with available Expressed Sequence Tag (EST) data. These tag-based technologies, which do not require a priori knowledge of genomic sequence, are well-suited for transcriptional profiling. The sequence depth of MPSS allowed us to capture and quantify almost all the transcripts at a specific stage in the development of the grape berry. The number and relative abundance of transcripts from stage II grape berries was defined using Massively Parallel Signature Sequencing (MPSS). A total of 2,635,293 17-base and 2,259,286 20-base signatures were obtained, representing at least 30,737 and 26,878 distinct sequences. The average normalized abundance per signature was approximately 49 TPM (Transcripts Per Million). Comparisons of the MPSS signatures with available Vitis species' ESTs and a unigene set demonstrated that 6,430 distinct contigs and 2,190 singletons have a perfect match to at least one MPSS signature. Among the matched sequences, ESTs were identified from tissues other than berries or from berries at different developmental stages. Additional MPSS signatures not matching to known grape ESTs can extend our knowledge of the V. vinifera transcriptome, particularly when these data are used to assist in annotation of whole genome sequences from Vitis vinifera. The MPSS data presented here not only achieved a higher level of saturation than previous EST based analyses, but in doing so, expand the known set of transcripts of grape berries during the unique stage in development that immediately precedes the onset of ripening. The MPSS dataset also revealed evidence of antisense expression not previously reported in grapes but comparable to that reported in other plant species. Finally, we developed a novel web-based, public resource for utilization of the grape MPSS data [1].

PSI-Center Final Progress Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Evolution of PCDD/F-signatures during mechanochemical degradation in municipal solid waste incineration filter ash.

PubMed

Zhiliang, Chen; Minghui, Tang; Shengyong, Lu; Jiamin, Ding; Qili, Qiu; Yuting, Wang; Jianhua, Yan

2018-05-28

Mechanochemical degradation (MCD) is employed for the dechlorination of polychlorinated dibenzo-p-dioxins (PCDD) and -furans (PCDF) in filter ashes from municipal solid waste incinerators, respectively with the assist of six additive systems. The evolution of PCDD/F-signatures in all eleven samples are systematically monitored and studied at the level of individual congeners, and special attention is paid to CP-route congeners, 2,3,7,8-substitution, 1,9-substitution, and 4,6-PCDF. The PCDD/F-isomers distribution follows an analogous pattern, indicating the similar acting mechanism for all additives: additives transfer electrons to attack the CCl bond and then expulse chlorine. MC dechlorination is not favored for the chlorine on β-position (2,3,7,8-position). The oxygen with stronger electronegativity in PCDD/Fs negatively influences CCl bond to accept donated electrons, hindering the removal of chlorine on 1,9-position for PCDD, and chlroine on 4,6-position for PCDF. Finally, two fair dechlorination pathways for PCDD and PCDF are respectively proposed based on the detailed analysis of CP-route congeners. The evolution of PCDD-signatures is clear, yet obscure for PCDF-signatures, which still requires further investigations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Detecting and visualizing weak signatures in hyperspectral data

NASA Astrophysics Data System (ADS)

MacPherson, Duncan James

This thesis evaluates existing techniques for detecting weak spectral signatures from remotely sensed hyperspectral data. Algorithms are presented that successfully detect hard-to-find 'mystery' signatures in unknown cluttered backgrounds. The term 'mystery' is used to describe a scenario where the spectral target and background endmembers are unknown. Sub-Pixel analysis and background suppression are used to find deeply embedded signatures which can be less than 10% of the total signal strength. Existing 'mystery target' detection algorithms are derived and compared. Several techniques are shown to be superior both visually and quantitatively. Detection performance is evaluated using confidence metrics that are developed. A multiple algorithm approach is shown to improve detection confidence significantly. Although the research focuses on remote sensing applications, the algorithms presented can be applied to a wide variety of diverse fields such as medicine, law enforcement, manufacturing, earth science, food production, and astrophysics. The algorithms are shown to be general and can be applied to both the reflective and emissive parts of the electromagnetic spectrum. The application scope is a broad one and the final results open new opportunities for many specific applications including: land mine detection, pollution and hazardous waste detection, crop abundance calculations, volcanic activity monitoring, detecting diseases in food, automobile or airplane target recognition, cancer detection, mining operations, extracting galactic gas emissions, etc.

Research progress on electronic phase separation in low-dimensional perovskite manganite nanostructures

PubMed Central

2014-01-01

Perovskite oxide manganites with a general formula of R1-x AxMnO3 (where R is a trivalent rare-earth element such as La, Pr, Sm, and A is a divalent alkaline-earth element such as Ca, Sr, and Ba) have received much attention due to their unusual electron-transport and magnetic properties, which are indispensable for applications in microelectronic, magnetic, and spintronic devices. Recent advances in the science and technology have resulted in the feature sizes of microelectronic devices based on perovskite manganite oxides down-scaling into nanoscale dimensions. At the nanoscale, low-dimensional perovskite manganite oxide nanostructures display novel physical properties that are different from their bulk and film counterparts. Recently, there is strong experimental evidence to indicate that the low-dimensional perovskite manganite oxide nanostructures are electronically inhomogeneous, consisting of different spatial regions with different electronic orders, a phenomenon that is named as electronic phase separation (EPS). As the geometry sizes of the low-dimensional manganite nanostructures are reduced to the characteristic EPS length scale (typically several tens of nanometers in manganites), the EPS is expected to be strongly modulated, leading to quite dramatic changes in functionality and more emergent phenomena. Therefore, reduced dimensionality opens a door to the new functionalities in perovskite manganite oxides and offers a way to gain new insight into the nature of EPS. During the past few years, much progress has been made in understanding the physical nature of the EPS in low-dimensional perovskite manganite nanostructures both from experimentalists and theorists, which have a profound impact on the oxide nanoelectronics. This nanoreview covers the research progresses of the EPS in low-dimensional perovskite manganite nanostructures such as nanoparticles, nanowires/nanotubes, and nanostructured films and/or patterns. The possible physical origins of the EPS are also discussed from the signatures of electronic inhomogeneities as well as some theoretical scenarios, to shed light on understanding this phenomenon. Finally, the perspectives to the future researches in this area are also outlined. PMID:25024686

Early diagnostic of concurrent gear degradation processes progressing under time-varying loads

NASA Astrophysics Data System (ADS)

Guilbault, Raynald; Lalonde, Sébastien

2016-08-01

This study develops a gear diagnostic procedure for the detection of multi- and concurrent degradation processes evolving under time-varying loads. Instead of a conventional comparison between a descriptor and an alarm level, this procedure bases its detection strategy on a descriptor evolution tracking; a lasting descriptor increase denotes the presence of ongoing degradation mechanisms. The procedure works from time domain residual signals prepared in the frequency domain, and accepts any gear conditions as reference signature. To extract the load fluctuation repercussions, the procedure integrates a scaling factor. The investigation first examines a simplification assuming a linear connection between the load and the dynamic response amplitudes. However, while generally valuable, the precision losses associated with large load variations may mask the contribution of tiny flaws. To better reflect the real non-linear relation, the paper reformulates the scaling factor; a power law with an exponent value of 0.85 produces noticeable improvements of the load effect extraction. To reduce the consequences of remaining oscillations, the procedure also includes a filtering phase. During the validation program, a synthetic wear progression assuming a commensurate relation between the wear depth and friction assured controlled evolutions of the surface degradation influence, whereas the fillet crack growth remained entirely determined by the operation conditions. Globally, the tested conditions attest that the final strategy provides accurate monitoring of coexisting isolated damages and general surface deterioration, and that its tracking-detection capacities are unaffected by severe time variations of external loads. The procedure promptly detects the presence of evolving abnormal phenomena. The tests show that the descriptor curve shapes virtually describe the constant wear progression superimposed on the crack length evolution. At the tooth fracture, the mean values of the residual signal evince strong perturbations, while after this episode, the monitoring curves continue signaling the ongoing wear process.

Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy

PubMed Central

Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano

2016-01-01

Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID:27073865

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

PubMed

Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

2013-01-01

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

NASA Technical Reports Server (NTRS)

Rana, Brinda K.; Stenger, Michael B.; Lee, Stuart M. C.; Macias, Brandon R.; Siamwala, Jamila; Piening, Brian Donald; Hook, Vivian; Ebert, Doug; Patel, Hemal; Smith, Scott;

Signature and Mechanism of the Epitehlial-to-Mesenchymal Transition. Addendum

DTIC Science & Technology

2011-09-01

as breast cancer . This study seeks to identify genes commonly regulated in the EMT, and identify key regulators of the process. An EMT core gene...Introduction Breast cancer is the most common form of cancer in women in the United States (1). Mortality results not from the primary tumor, but from...complications arising from metastases that have spread beyond the breast itself. Hence, the study of breast cancer progression and metastasis is

In-depth analysis and characterization of a dual damascene process with respect to different CD

NASA Astrophysics Data System (ADS)

Krause, Gerd; Hofmann, Detlef; Habets, Boris; Buhl, Stefan; Gutsch, Manuela; Lopez-Gomez, Alberto; Kim, Wan-Soo; Thrun, Xaver

2018-03-01

In a 200 mm high volume environment, we studied data from a dual damascene process. Dual damascene is a combination of lithography, etch and CMP that is used to create copper lines and contacts in one single step. During these process steps, different metal CD are measured by different measurement methods. In this study, we analyze the key numbers of the different measurements after different process steps and develop simple models to predict the electrical behavior* . In addition, radial profiles have been analyzed of both inline measurement parameters and electrical parameters. A matching method was developed based on inline and electrical data. Finally, correlation analysis for radial signatures is presented that can be used to predict excursions in electrical signatures.

Laser vibrometry exploitation for vehicle identification

NASA Astrophysics Data System (ADS)

Nolan, Adam; Lingg, Andrew; Goley, Steve; Sigmund, Kevin; Kangas, Scott

2014-06-01

Vibration signatures sensed from distant vehicles using laser vibrometry systems provide valuable information that may be used to help identify key vehicle features such as engine type, engine speed, and number of cylinders. Through the use of physics models of the vibration phenomenology, features are chosen to support classification algorithms. Various individual exploitation algorithms were developed using these models to classify vibration signatures into engine type (piston vs. turbine), engine configuration (Inline 4 vs. Inline 6 vs. V6 vs. V8 vs. V12) and vehicle type. The results of these algorithms will be presented for an 8 class problem. Finally, the benefits of using a factor graph representation to link these independent algorithms together will be presented which constructs a classification hierarchy for the vibration exploitation problem.

Development of a nondestructive vibration technique for bond assessment of Space Shuttle tiles

NASA Technical Reports Server (NTRS)

Moslehy, Faissal A.

1994-01-01

This final report describes the achievements of the above titled project. The project is funded by NASA-KSC (Grant No. NAG 10-0117) for the period of 1 Jan. to 31 Dec. 1993. The purpose of this project was to develop a nondestructive, noncontact technique based on 'vibration signature' of tile systems to quantify the bond conditions of the thermal protection system) tiles of Space Shuttle orbiters. The technique uses a laser rapid scan system, modal measurements, and finite element modeling. Finite element models were developed for tiles bonded to both clamped and deformable integrated skin-stringer orbiter mid-fuselage. Results showed that the size and location of a disbonded tile can be determined from frequency and mode shape information. Moreover, a frequency response survey was used to quickly identify the disbonded tiles. The finite element results were compared with experimentally determined frequency responses of a 17-tile test panel, where a rapidscan laser system was employed. An excellent degree of correlation between the mathematical simulation and experimental results was realized. An inverse solution for single-tile assemblies was also derived and is being implemented into a computer program that can interact with the modal testing software. The output of the program displays the size and location of disbond. This program has been tested with simulated input (i.e., finite element data), and excellent agreement between predicted and simulated disbonds was shown. Finally, laser vibration imaging and acoustic emission techniques were shown to be well suited for detecting and monitoring the progressive damage in Graphite/Epoxy composite materials.

Fano Description of Single-Hydrocarbon Fluorescence Excited by a Scanning Tunneling Microscope.

PubMed

Kröger, Jörg; Doppagne, Benjamin; Scheurer, Fabrice; Schull, Guillaume

2018-06-13

The detection of fluorescence with submolecular resolution enables the exploration of spatially varying photon yields and vibronic properties at the single-molecule level. By placing individual polycyclic aromatic hydrocarbon molecules into the plasmon cavity formed by the tip of a scanning tunneling microscope and a NaCl-covered Ag(111) surface, molecular light emission spectra are obtained that unravel vibrational progression. In addition, light spectra unveil a signature of the molecule even when the tunneling current is injected well separated from the molecular emitter. This signature exhibits a distance-dependent Fano profile that reflects the subtle interplay between inelastic tunneling electrons, the molecular exciton and localized plasmons in at-distance as well as on-molecule fluorescence. The presented findings open the path to luminescence of a different class of molecules than investigated before and contribute to the understanding of single-molecule luminescence at surfaces in a unified picture.

Satellite traces: An ionogram signature for large-scale wave structure and a precursor for equatorial spread F

NASA Astrophysics Data System (ADS)

Tsunoda, Roland T.

2008-10-01

Although the source that controls day-to-day variability in the occurrence of equatorial plasma structure (i.e., equatorial spread F, or ESF) remains to be identified, progress is being made. There is evidence that the appearance of large-scale wave structure (LSWS) in the bottomside F layer, around the time of its post-sunset rise (PSSR), is a more-direct precursor of ESF than the PSSR itself. The bulk of the evidence, however, is in the form of ``satellite'' F traces in ionograms, which may be viewed as less than convincing, because these signatures have not been shown to be causally related to LSWS. In this paper, incoherent-scatter radar and ionosonde data, both collected on 24 July 1979 from the Kwajalein atoll, Marshall Islands, are used to show that this is indeed the case.

Direct weak localization signature with ultracold atoms: the CBS revival

NASA Astrophysics Data System (ADS)

Josse, Vincent

2016-05-01

Ultracold atomic systems in presence of disorder have attracted a lot of interest over the past decade, in particular to study the physics of Anderson localization (AL) in a renewed perspective. Landmark experiments have been demonstrated, in 1D and 3D geometries. However many challenges remain and new ideas have emerged, as for instance the search for original signatures of Anderson localization in momentum space. Here I will describe our progresses along that line where a weak localization effect has been directly observed, i.e. the Coherent Backscattering (CBS) phenomenon. In particular I will report on the recent observation of suppression and revival of CBS when a controlled dephasing kick is applied to the system. This observation demonstrates a novel and general method, introduced by T. Micklitz and coworkers, to study probe phase coherence in disordered systems by manipulating time reversal symmetry.

Brain structural, neurochemical and neuroinflammatory markers of psychosis onset and relapse: Is there evidence for a psychosis relapse signature?

PubMed

Cropley, Vanessa; Wood, Stephen J; Pantelis, Christos

2013-05-10

Schizophrenia is a debilitating illness that is often associated with progressive clinical deterioration following repeated episodes of illness. Despite the clinical evidence for clinical attrition, the nature of any associated neurobiological pathology has not been examined systematically. This review examines the neurobiological imaging markers associated with psychosis onset and relapse and considers whether these may be potential state markers of acute psychosis. We report several markers of neurobiological changes associated with acute psychosis. These include dynamic changes in brain structure in the frontal and temporal regions, neurochemical alterations in dopamine and glutamate and evidence for neuroinflammation through microglial activation. We propose that with the use of repeat longitudinal assessments of brain imaging markers over the course of a psychosis relapse, the neurobiological trajectory indicative of a 'relapse signature' for psychosis will be identified.

A BAP1 Mutation-specific MicroRNA Signature Predicts Clinical Outcomes in Clear Cell Renal Cell Carcinoma Patients with Wild-type BAP1

PubMed Central

Ge, Yu-Zheng; Xu, Lu-Wei; Zhou, Chang-Cheng; Lu, Tian-Ze; Yao, Wen-Tao; Wu, Ran; Zhao, You-Cai; Xu, Xiao; Hu, Zhi-Kai; Wang, Min; Yang, Xiao-Bing; Zhou, Liu-Hua; Zhong, Bing; Xu, Zheng; Li, Wen-Cheng; Zhu, Jia-Geng; Jia, Rui-Peng

2017-01-01

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1. PMID:28900502

Guaranteed Time Observations Support for Goddard High Resolution Spectrograph (GHRS) on HST

NASA Technical Reports Server (NTRS)

Beaver, Edward

1998-01-01

We assemble this final grant report by combining our previously submitted progress reports with the last year's progress report. Section 2 is the progress report for the June 1, 1991 to Nov. 14, 1995 period. Section 4 is the progress report for the Nov. 14, 1996 to Dec. 31, 1996 period. Section 5 is the progress report for the Nov. 14 to Aug. 31, 1997 period. Section 6 is the new progress report for the Sept. 15, 1997 to Nov. 14, 1998 final period. Section 3 is a summary of our spare detector high voltage transient tests activity in 1992 in support of the renewed safe operation of the GHRS HST D1 detector. Note that we have left the format of each progress report the same as originally sent out. The slight differences in format presentation are thus intended.

Assessment of Human Performance in a Simulated Rotorcraft Downwash Environment

DTIC Science & Technology

2007-05-01

Plaga Biosciences and Protection Division Biomechanics Branch May 2007 Final Report for December 2004 to August 2005... Biomechanics Branch Wright-Patterson AFB OH 45433-7947 Approved for public release; distribution is unlimited NOTICE AND SIGNATURE PAGE...Human Effectiveness Directorate Biosciences & Protection Division Biomechanics Branch Wright-Patterson AFB OH 45433-7947 11. SPONSOR/MONITOR’S

Utilization of Skylab (EREP) system for appraising changes in continental migratory bird habitat

USGS Publications Warehouse

Work, E.A.; Gilmer, D.S.

1975-01-01

The author has identified the following significant results. Surface water statistics using data obtained by supporting aircraft were generated. Signature extraction and refinement preliminary to wetland and associated upland vegetation recognition were accomplished, using a selected portion of the aircraft data. Final classification mapping and analysis of surface water trends will be accomplished.

Districts Shun Stimulus Bids

ERIC Educational Resources Information Center

Maxwell, Lesli A.

2010-01-01

In the final sprint to polish Race to the Top applications, hundreds of school districts shunned a shot at a share of $4 billion in grants by refusing to sign on to their states' plans for the federal competition. California officials had secured the signatures of 790 local education agencies (leas) late last week, including most of the state's…

Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers.

PubMed

Klimov, Sergey; Rida, Padmashree Cg; Aleskandarany, Mohammed A; Green, Andrew R; Ellis, Ian O; Janssen, Emiel Am; Rakha, Emad A; Aneja, Ritu

2017-09-05

Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most common underlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis. Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiple variables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis. This study aimed at identifying a biomarker signature to predict particular sites of DM in TNBC. A clinically annotated series of 322 TNBC were immunohistochemically stained with 133 biomarkers relevant to BC, to develop multibiomarker models for predicting metastasis to the bone, liver, lung and brain. Patients who experienced metastasis to each site were compared with those who did not, by gradually filtering the biomarker set via a two-tailed t-test and Cox univariate analyses. Biomarker combinations were finally ranked based on statistical significance, and evaluated in multivariable analyses. Our final models were able to stratify TNBC patients into high risk groups that showed over 5, 6, 7 and 8 times higher risk of developing metastasis to the bone, liver, lung and brain, respectively, than low-risk subgroups. These models for predicting site-specific metastasis retained significance following adjustment for tumour size, patient age and chemotherapy status. Our novel IHC-based biomarkers signatures, when assessed in primary TNBC tumours, enable prediction of specific sites of metastasis, and potentially unravel biomarkers previously unknown in site tropism.

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells

PubMed Central

Luckey, Chance John; Bhattacharya, Deepta; Goldrath, Ananda W.; Weissman, Irving L.; Benoist, Christophe; Mathis, Diane

2006-01-01

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. PMID:16492737

Event identification by acoustic signature recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dress, W.B.; Kercel, S.W.

1995-07-01

Many events of interest to the security commnnity produce acoustic emissions that are, in principle, identifiable as to cause. Some obvious examples are gunshots, breaking glass, takeoffs and landings of small aircraft, vehicular engine noises, footsteps (high frequencies when on gravel, very low frequencies. when on soil), and voices (whispers to shouts). We are investigating wavelet-based methods to extract unique features of such events for classification and identification. We also discuss methods of classification and pattern recognition specifically tailored for acoustic signatures obtained by wavelet analysis. The paper is divided into three parts: completed work, work in progress, and futuremore » applications. The completed phase has led to the successful recognition of aircraft types on landing and takeoff. Both small aircraft (twin-engine turboprop) and large (commercial airliners) were included in the study. The project considered the design of a small, field-deployable, inexpensive device. The techniques developed during the aircraft identification phase were then adapted to a multispectral electromagnetic interference monitoring device now deployed in a nuclear power plant. This is a general-purpose wavelet analysis engine, spanning 14 octaves, and can be adapted for other specific tasks. Work in progress is focused on applying the methods previously developed to speaker identification. Some of the problems to be overcome include recognition of sounds as voice patterns and as distinct from possible background noises (e.g., music), as well as identification of the speaker from a short-duration voice sample. A generalization of the completed work and the work in progress is a device capable of classifying any number of acoustic events-particularly quasi-stationary events such as engine noises and voices and singular events such as gunshots and breaking glass. We will show examples of both kinds of events and discuss their recognition likelihood.« less

Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease

PubMed Central

Macías-Segura, N.; Bastian, Y.; Santiago-Algarra, D.; Castillo-Ortiz, J. D.; Alemán-Navarro, A. L.; Jaime-Sánchez, E.; Gomez-Moreno, M.; Saucedo-Toral, C. A.; Lara-Ramírez, Edgar E.; Zapata-Zuñiga, M.; Enciso-Moreno, L.; González-Amaro, R.; Ramos-Remus, C.; Enciso-Moreno, J. A.

2018-01-01

Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage. Some of these particular up-regulated and down-regulated genes are related to inflammatory processes and could be considered as biomarker candidates for disease progression in subjects at risk to develop RA. PMID:29584756

An Identity-Based Anti-Quantum Privacy-Preserving Blind Authentication in Wireless Sensor Networks.

PubMed

Zhu, Hongfei; Tan, Yu-An; Zhu, Liehuang; Wang, Xianmin; Zhang, Quanxin; Li, Yuanzhang

2018-05-22

With the development of wireless sensor networks, IoT devices are crucial for the Smart City; these devices change people's lives such as e-payment and e-voting systems. However, in these two systems, the state-of-art authentication protocols based on traditional number theory cannot defeat a quantum computer attack. In order to protect user privacy and guarantee trustworthy of big data, we propose a new identity-based blind signature scheme based on number theorem research unit lattice, this scheme mainly uses a rejection sampling theorem instead of constructing a trapdoor. Meanwhile, this scheme does not depend on complex public key infrastructure and can resist quantum computer attack. Then we design an e-payment protocol using the proposed scheme. Furthermore, we prove our scheme is secure in the random oracle, and satisfies confidentiality, integrity, and non-repudiation. Finally, we demonstrate that the proposed scheme outperforms the other traditional existing identity-based blind signature schemes in signing speed and verification speed, outperforms the other lattice-based blind signature in signing speed, verification speed, and signing secret key size.

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

PubMed

Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

2018-03-15

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

An Identity-Based Anti-Quantum Privacy-Preserving Blind Authentication in Wireless Sensor Networks

PubMed Central

Zhu, Hongfei; Tan, Yu-an; Zhu, Liehuang; Wang, Xianmin; Zhang, Quanxin; Li, Yuanzhang

2018-01-01

With the development of wireless sensor networks, IoT devices are crucial for the Smart City; these devices change people’s lives such as e-payment and e-voting systems. However, in these two systems, the state-of-art authentication protocols based on traditional number theory cannot defeat a quantum computer attack. In order to protect user privacy and guarantee trustworthy of big data, we propose a new identity-based blind signature scheme based on number theorem research unit lattice, this scheme mainly uses a rejection sampling theorem instead of constructing a trapdoor. Meanwhile, this scheme does not depend on complex public key infrastructure and can resist quantum computer attack. Then we design an e-payment protocol using the proposed scheme. Furthermore, we prove our scheme is secure in the random oracle, and satisfies confidentiality, integrity, and non-repudiation. Finally, we demonstrate that the proposed scheme outperforms the other traditional existing identity-based blind signature schemes in signing speed and verification speed, outperforms the other lattice-based blind signature in signing speed, verification speed, and signing secret key size. PMID:29789475

Transcription instability in high-risk neuroblastoma is associated with a global perturbation of chromatin domains.

PubMed

Zanon, Carlo; Tonini, Gian Paolo

2017-11-01

Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN-signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN-signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Carotenoid Distribution in Living Cells of Haematococcus pluvialis (Chlorophyceae)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, Aaron M.; Jones, Howland D. T.; Han, Danxiang

Haematococcus pluvialis is a freshwater unicellular green microalga belonging to the class Chlorophyceae and is of commercial interest for its ability to accumulate massive amounts of the red ketocarotenoid astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione). Using confocal Raman microscopy and multivariate analysis, we demonstrate the ability to spectrally resolve resonance–enhanced Raman signatures associated with astaxanthin and β-carotene along with chlorophyll fluorescence. By mathematically isolating these spectral signatures, in turn, it is possible to locate these species independent of each other in living cells of H. pluvialis in various stages of the life cycle. Chlorophyll emission was found only in the chloroplast whereas astaxanthin wasmore » identified within globular and punctate regions of the cytoplasmic space. Moreover, we found evidence for β-carotene to be co-located with both the chloroplast and astaxanthin in the cytosol. These observations imply that β-carotene is a precursor for astaxanthin and the synthesis of astaxanthin occurs outside the chloroplast. Finally, our work demonstrates the broad utility of confocal Raman microscopy to resolve spectral signatures of highly similar chromophores in living cells.« less

Probing the coupling of heavy dark matter to nucleons by detecting neutrino signature from the Earth's core

NASA Astrophysics Data System (ADS)

Lin, Guey-Lin; Lin, Yen-Hsun; Lee, Fei-Fan

2015-02-01

We argue that the detection of the neutrino signature from the Earth's core can effectively probe the coupling of heavy dark matter (mχ>104 GeV ) to nucleons. We first note that direct searches for dark matter (DM) in such a mass range provide much less stringent constraint than the constraint provided by such searches for mχ˜100 GeV . Furthermore, the energies of neutrinos arising from DM annihilation inside the Sun cannot exceed a few TeVs at the Sun's surface due to the attenuation effect. Therefore, the sensitivity to the heavy DM coupling is lost. Finally, the detection of the neutrino signature from the Galactic halo can only probe DM annihilation cross sections. We present neutrino event rates in IceCube and KM3NeT arising from the neutrino flux produced by annihilation of Earth-captured DM heavier than 104 GeV . The IceCube and KM3NeT sensitivities to spin-independent DM-proton scattering cross section σχ p in this mass range are presented for both isospin-symmetric and isospin-violating cases.

Targeting Renal Cell Carcinoma with a HIF-2 antagonist

PubMed Central

Chen, Wenfang; Hill, Haley; Christie, Alana; Kim, Min Soo; Holloman, Eboni; Pavia-Jimenez, Andrea; Homayoun, Farrah; Ma, Yuanqing; Patel, Nirav; Yell, Paul; Hao, Guiyang; Yousuf, Qurratulain; Joyce, Allison; Pedrosa, Ivan; Geiger, Heather; Zhang, He; Chang, Jenny; Gardner, Kevin H.; Bruick, Richard K.; Reeves, Catherine; Hwang, Tae Hyun; Courtney, Kevin; Frenkel, Eugene; Sun, Xiankai; Zojwalla, Naseem; Wong, Tai; Rizzi, James P.; Wallace, Eli M.; Josey, John A.; Xie, Yang; Xie, Xian-Jin; Kapur, Payal; McKay, Renée M.; Brugarolas, James

2016-01-01

Clear cell Renal Cell Carcinoma (ccRCC) is characterized by VHL inactivation1,2. Because no other gene is mutated as frequently, and VHL mutations are truncal3, VHL inactivation is regarded as the governing event4. VHL loss activates HIF-2, and constitutive HIF-2 restores tumorigenesis in VHL-reconstituted ccRCC cells5. HIF-2 is implicated in angiogenesis and multiple other processes6–9, but angiogenesis is the main target of drugs like sunitinib10. HIF-2, a transcription factor, has been regarded as undruggable11. A structure-based design approach identified a selective HIF-2 antagonist (PT2399) that we evaluate using a tumorgraft (TG)/PDX platform12,13. PT2399 dissociated HIF-2 (an obligatory heterodimer [HIF-2α/HIF-1β])14 in human ccRCC suppressing tumorigenesis in 56% (10/18) lines. PT2399 had greater activity than sunitinib, was active in sunitinib-progressing tumors, and was better tolerated. Unexpectedly, some VHL-mutant ccRCCs were resistant. Resistance occurred despite HIF-2 dissociation in tumors and evidence of Hif-2 inhibition in the mouse as determined by suppression of circulating erythropoietin, a HIF-2 target15 and possible pharmacodynamic marker. We identified a HIF-2-dependent gene signature in sensitive tumors. Illustrating drug specificity, gene expression was largely unaffected by PT2399 in resistant tumors. Sensitive tumors exhibited a distinguishing gene expression signature, and generally higher HIF-2α levels. Prolonged PT2399 treatment led to resistance. We identified a binding site and second site suppressor mutation in HIF-2α and HIF-1β respectively. Both mutations preserved HIF-2 dimers despite treatment with PT2399. Finally, an extensively pretreated patient with a sensitive TG had disease control for >11 months with the close analogue PT2385. We validate HIF-2 as a target in ccRCC, show that some ccRCC are, unexpectedly, HIF-2 independent, and set the stage for biomarker-driven clinical trials. PMID:27595394

Hydrogen and oxygen isotope constraints on hydrothermal alteration of the Trinity peridotite, Klamath Mountains, California

USGS Publications Warehouse

Liakhovitch, V.; Quick, J.E.; Gregory, R.T.

2005-01-01

The Trinity peridotite represents a rare opportunity to examine a relatively fertile plagioclase peridotite that was exhumed and later subjected to intrusive events in a seafloor environment, followed by its emplacement and incorporation into a continent. Over 250 stable isotopic determinations on whole rocks and minerals elucidate the hydrothermal evolution of the Trinity complex. All three serpentine polymorphs are present in the Trinity peridotite; these separate on the basis of their ??D values: antigorite, -46 < ??D < -82??? and lizardite and chrysotile, -90 < ??D < -106 and -110 < ??D < -136???, respectively. Antigorite coexists with chlorite, talc, and tremolite in contact aureole assemblages associated with Silurian/Devonian gabbroic plutons. Lizardite and chrysotile alteration carries a meteoric signature, which suggests association with post-emplacement serpentinization, or overprinting of earlier low-temperature seafloor serpentinization. Regionally, contours of ??D values exhibit bull's-eye patterns associated with the gabbroic plutons, with ??D maxima coinciding with the blackwall alteration at the margins on the plutons. In contrast to the hydrogen isotope behavior, oxygen isotope values of the three polymorphs are indistinguishable, spanning the range 5.3 < ??18O< 7.5, and suggesting low integrated fluid fluxes and strongly 18O-shifted fluids. Inferred primary ?? 18O values for peridotite, gabbro, and late Mesozoic granodiorite indicate a progressive 18O enrichment with time for the source regions of the rocks. These isotopic signatures are consistent with the geology, petrochemistry, and geochronology of the Trinity massif, which indicate the following history: (1) lithospheric emplacement and cooling of the peridotite in an oceanic environment ??? 472 Ma; (2) intrusion of gabbroic plutons into cold peridotite in an arc environment between 435 and 404 Ma; and finally (3) intrusion of felsic plutons between 171 and 127 Ma, long after the peridotite was incorporated into the continental crust. Copyright ?? 2005 by V. H. Winston & Son, Inc. All rights reserved.

New Hafnium Isotope and Trace Element Constraints on the Role of a Plume in Genesis of the Eastern Snake River Plain Basalts, Idaho

NASA Astrophysics Data System (ADS)

Taylor, R. D.; Reid, M. R.; Blichert-Toft, J.

2009-12-01

Bimodal volcanism associated with the eastern Snake River Plain (ESRP)-Yellowstone Plateau province has persisted since approximately 16 Ma. A time-transgressive track of rhyolitic eruptions which young progressively to the east and parallel the motion of the North American plate are overlain by younger basalts with no age progression. Interpretations for the origin of these basalts range from a thermo-chemical mantle plume to incipient melting of the shallow upper mantle, and remain controversial. The enigmatic ESRP basalts are characterized by high 3He/4He, diagnostic of a plume source, but also by lithophile radiogenic isotope signatures that are more enriched than expected for plume-derived OIBs. These features could possibly be caused by isotopic decoupling associated with shallow melting of a hybridized upper mantle, or derivation from an atypical mantle plume, or both by way of mixing. New Hf isotope and trace element data further constrain potential sources for the ESRP basalts. Their Hf isotopic signatures (ɛHf = +0.1 to -5.8) are moderately enriched and consistently fall above or in the upper part of the field of OIBs, with similar Nd isotope signatures (ɛNd = -2.0 to -5.8), indicating a source with high time-integrated Lu/Hf compared with Sm/Nd. The isotopic compositions of the basalts lie between those of Archean SCML and a more depleted end-member source, suggestive of contributions from at least two sources. The grouping of isotopic characteristics is compact compared to other regional volcanism, implying that the hybridization process is highly reproducible within the ESRP. Minor localized differences in isotopic composition may signify local variations in the relative proportions of the end-members. Trace element patterns also support genesis of the ESRP basalts from an enriched source. Our data detect evidence of deeper contributions derived from the garnet-stability field, and a greater affinity of the trace element signatures to plume sources than to sources in the mantle lithosphere. The Hf isotope and trace element characteristics of the ESRP basalts thus support a model of derivation from a deep mantle plume with additional melt contributions and isotopic overprinting from SCML.

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation.

PubMed

Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

2016-10-12

Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

Application of gold compositional analyses to mineral exploration in the United States

USGS Publications Warehouse

Antweiler, J.C.; Campbell, W.L.

1977-01-01

Native gold is a mineral composed of Au, Ag and Cu in solid solution and it usually contains one or more trace metals as lattice impurities, as mineral inclusions, in grain boundaries or in surface coatings. Alloy proportions of Au, Ag and Cu, together with certain other elements, can be thought of as constituting a gold "signature". Gold is associated with a great variety of ore deposits and has characteristic signatures for each of several types of ore deposits. Signatures for gold derived from igneous-metamorphic, hypothermal, mesothermal and epithermal deposits reflect conditions of ore formation by their content of Ag, Cu and characteristic associated elements. At higher temperatures of ore formation, gold has low Ag and high Cu content, and Bi and Pb are the most abundant trace elements. But at lower temperatures of ore formation, Ag is high, Cu is low, and Pb is the most abundant trace element. The same trend in gold signatures is observable in gold mining districts, such as Central City, Colorado, where zoning as shown by mineral assemblages indicates ore deposition at progressively lower temperatures as the distance from a central high-temperature zone increases. The signatures of gold may be useful in searching for porphyry Cu deposits. Signatures from Butte (Montana), Mineral Park (Arizona) and Cala Abajo (Puerto Rico), on the basis of limited sampling, are similar and distinctive. They are characterized by a similar assemblage of trace elements and are relatively high in both Ag and Cu. Another application of gold compositional data is in tracing placer gold to its bedrock source. For example, the Ag content of placer gold in the Tarryall district of Colorado differed from that of nearly all of the bedrock sources of gold found by early prospectors. However, one lightly prospected area peripheral to the Tertiary quartz monzonite stock at Montgomery Gulch contains gold with a Ag content similar to that of the placer gold. This area is the most likely source of the gold in the productive placers and may be a potential exploration target. Gold signatures may be useful in prospecting for metals other than gold. Several metals of low crustal abundance - notably Sn, W, Mo and the Pt group metals - are detected in analyses of some gold samples and may indicate economic deposits of these metals. ?? 1977.

Recent Progress on GRBs with Swift

NASA Technical Reports Server (NTRS)

Gehrels, N.; Cannizzo, J. K.

2010-01-01

We are in an exciting period of discovery for gamma-ray bursts. The Swift observatory is detecting 100 bursts per year, providing arcsecond localizations and sensitive observations of the prompt and afterglow emission. In addition, rapid-response telescopes on the ground have new capabilities to study optical emission during the prompt phase and spectral signatures of the host galaxies. The combined data set is enabling great advances in our understanding of GRBs including afterglow physics, short burst origin, and supernova physics.

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

Longitudinal study of cellular and systemic cytokines signatures define the dynamics of a balanced immune environment in disease manifestation in Zika virus-infected patients.

PubMed

Lum, Fok-Moon; Lye, David C B; Tan, Jeslin J L; Lee, Bernett; Chia, Po-Ying; Chua, Tze-Kwang; Amrun, Siti N; Kam, Yiu-Wing; Yee, Wearn-Xin; Ling, Wei-Ping; Lim, Vanessa W X; Pang, Vincent J X; Lee, Linda K; Mok, Esther W H; Chong, Chia-Yin; Leo, Yee-Sin; Ng, Lisa F P

2018-04-16

The unexpected re-emergence of Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex micro-bead assay, while changes in blood cell numbers were determined with immune-phenotyping. Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of IP-10, MCP-1, IL-1RA, IL-8 and PIGF-1, accompanied by reduced numbers of peripheral CD8+, CD4+ and DNT cells. Levels of T-cell associated mediators including IP-10, IFNγ, and IL-10 were high in recovery phases of ZIKV infection, suggesting a functional role for T-cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression and provides valuable insights into ZIKV immuno-pathogenesis.

Molecular Biomarkers of Cancer Stem/Progenitor Cells Associated with Progression, Metastases, and Treatment Resistance of Aggressive Cancers

PubMed Central

Mimeault, Murielle; Batra, Surinder K.

2014-01-01

The validation of novel diagnostic, prognostic, and predictive biomarkers and therapeutic targets in tumor cells is of critical importance for optimizing the choice and efficacy of personalized therapies. Importantly, recent advances have led to the identification of gene-expression signatures in cancer cells, including cancer stem/progenitor cells, in the primary tumors, exosomes, circulating tumor cells (CTC), and disseminated cancer cells at distant metastatic sites. The gene-expression signatures may help to improve the accuracy of diagnosis and predict the therapeutic responses and overall survival of patients with cancer. Potential biomarkers in cancer cells include stem cell–like markers [CD133, aldehyde dehydrogenase (ALDH), CD44, and CD24], growth factors, and their cognate receptors [epidermal growth factor receptor (EGFR), EGFRvIII, and HER2], molecules associated with epithelial–mesenchymal transition (EMT; vimentin, N-cadherin, snail, twist, and Zeb1), regulators of altered metabolism (phosphatidylinositol-3′ kinase/Akt/mTOR), and drug resistance (multidrug transporters and macrophage inhibitory cytokine-1). Moreover, different pluripotency-associated transcription factors (Oct3/4, Nanog, Sox2, and Myc) and microRNAs that are involved in the epigenetic reprogramming and acquisition of stem cell–like properties by cancer cells during cancer progression may also be exploited as molecular biomarkers to predict the risk of metastases, systemic treatment resistance, and disease relapse of patients with cancer. PMID:24273063

A Mixed-Fidelity Approach for Design of Low-Boom Supersonic Aircraft

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood; Geiselhart, Karl A.

2010-01-01

This paper documents a mixed-fidelity approach for the design of low-boom supersonic aircraft as a viable approach for designing a practical low-boom supersonic configuration. A low-boom configuration that is based on low-fidelity analysis is used as the baseline. Tail lift is included to help tailor the aft portion of the ground signature. A comparison of low- and high-fidelity analysis results demonstrates the necessity of using computational fluid dynamics (CFD) analysis in a low-boom supersonic configuration design process. The fuselage shape is modified iteratively to obtain a configuration with a CFD equivalent-area distribution that matches a predetermined low-boom target distribution. The mixed-fidelity approach can easily refine the low-fidelity low-boom baseline into a low-boom configuration with the use of CFD equivalent-area analysis. The ground signature of the final configuration is calculated by using a state-of-the-art CFD-based boom analysis method that generates accurate midfield pressure distributions for propagation to the ground with ray tracing. The ground signature that is propagated from a midfield pressure distribution has a shaped ramp front, which is similar to the ground signature that is propagated from the CFD equivalent-area distribution. This result confirms the validity of the low-boom supersonic configuration design by matching a low-boom equivalent-area target, which is easier to accomplish than matching a low-boom midfield pressure target.

Oxidation and Hydration of U 3O 8 Materials Following Controlled Exposure to Temperature and Humidity

DOE PAGES

Tamasi, Alison L.; Boland, Kevin S.; Czerwinski, Kenneth; ...

2015-03-18

Chemical signatures correlated with uranium oxide processing are of interest to forensic science for inferring sample provenance. Identification of temporal changes in chemical structures of process uranium materials as a function of controlled temperatures and relative humidities may provide additional information regarding sample history. In our study, a high-purity α-U 3O 8 sample and three other uranium oxide samples synthesized from reaction routes used in nuclear conversion processes were stored under controlled conditions over 2–3.5 years, and powder X-ray diffraction analysis and X-ray absorption spectroscopy were employed to characterize chemical speciation. We measured signatures from the α-U 3O 8 samplemore » indicated that the material oxidized and hydrated after storage under high humidity conditions over time. Impurities, such as uranyl fluoride or schoepites, were initially detectable in the other uranium oxide samples. After storage under controlled conditions, the analyses of the samples revealed oxidation over time, although the signature of the uranyl fluoride impurity diminished. The presence of schoepite phases in older uranium oxide material is likely indicative of storage under high humidity and should be taken into account for assessing sample history. Finally, the absence of a signature from a chemical impurity, such as uranyl fluoride hydrate, in an older material may not preclude its presence at the initial time of production.« less

Water at silica/liquid water interfaces investigated by DFT-MD simulations

NASA Astrophysics Data System (ADS)

Gaigeot, Marie-Pierre

This talk is dedicated to probing the microscopic structural organization of water at silica/liquid water interfaces including electrolytes by first principles DFT-based molecular dynamics simulations (DFT-MD). We will present our very recent DFT-MD simulations of electrolytic (KCl, NaCl, NaI) silica/liquid water interfaces in order to unravel the intertwined structural properties of water and electrolytes at the crystalline quartz/liquid water and amorphous silica/liquid water interfaces. DFT-MD simulations provide direct knowledge of the structural organization of water and the H-Bond network formed between the water molecules within the different water layers above the silica surface. One can furthermore extract vibrational signatures of the water molecules within the interfacial layers from the DFT-MD simulations, especially non-linear SFG (Sum Frequency generation) signatures that are active at solid/liquid interfaces. The strength of the simulated spectra is that a detailed analysis of the signatures in terms of the water/water H-Bond networks formed within the interfacial water layers and in terms of the water/silica or water/electrolytes H-Bond networks can be given. Comparisons of SFG spectra between quartz/water/electrolytes and amorphous silica/water/electrolytes interfaces allow us to definitely conclude on how the structural arrangements of liquid water at these electrolytic interfaces modulate the final spectroscopic signatures. Invited speaker.

Development of a Process Signature for Manufacturing Processes with Thermal Loads

NASA Astrophysics Data System (ADS)

Frerichs, Friedhelm; Meyer, Heiner; Strunk, Rebecca; Kolkwitz, Benjamin; Epp, Jeremy

2018-06-01

The newly proposed concept of Process Signatures enables the comparison of seemingly different manufacturing processes via a process-independent approach based on the analysis of the loading condition and resulting material modification. This contribution compares the recently published results, based on numerically achieved data for the development of Process Signatures for sole surface and volume heatings without phase transformations, with the experimental data. The numerical approach applies the moving heat source theory in combination with energetic quantities. The external thermal loadings of both processes were characterized by the resulting temperature development, which correlates with a change in the residual stress state. The numerical investigations show that surface and volume heatings are interchangeable for certain parameter regimes regarding the changes in the residual stress state. Mainly, temperature gradients and thermal diffusion are responsible for the considered modifications. The applied surface- and volume-heating models are used in shallow cut grinding and induction heating, respectively. The comparison of numerical and experimental data reveals similarities, but also some systematic deviations of the residual stresses at the surface. The evaluation and final discussion support the assertion for very fast stress relaxation processes within the subsurface region. A consequence would be that the stress relaxation processes, which are not yet included in the numerical models, must be included in the Process Signatures for sole thermal impacts.

Wind Tunnel Model Design for Sonic Boom Studies of Nozzle Jet Flows with Shock Interactions

NASA Technical Reports Server (NTRS)

Cliff, Susan E.; Denison, Marie; Moini-Yekta, Shayan; Morr, Donald E.; Durston, Donald A.

2016-01-01

NASA and the U.S. aerospace industry are performing studies of supersonic aircraft concepts with low sonic boom pressure signatures. The computational analyses of modern aircraft designs have matured to the point where there is confidence in the prediction of the pressure signature from the front of the vehicle, but uncertainty remains in the aft signatures due to boundary layer and nozzle exhaust jet effects. Wind tunnel testing without inlet and nozzle exhaust jet effects at lower Reynolds numbers than in-flight make it difficult to accurately assess the computational solutions of flight vehicles. A wind tunnel test in the NASA Ames 9- by 7-Foot Supersonic Wind Tunnel is planned for February 2016 to address the nozzle jet effects on sonic boom. The experiment will provide pressure signatures of test articles that replicate waveforms from aircraft wings, tails, and aft fuselage (deck) components after passing through cold nozzle jet plumes. The data will provide a variety of nozzle plume and shock interactions for comparison with computational results. A large number of high-fidelity numerical simulations of a variety of shock generators were evaluated to define a reduced collection of suitable test models. The computational results of the candidate wind tunnel test models as they evolved are summarized, and pre-test computations of the final designs are provided.

The origin, evolution and signatures of primordial magnetic fields.

PubMed

Subramanian, Kandaswamy

2016-07-01

The universe is magnetized on all scales probed so far. On the largest scales, galaxies and galaxy clusters host magnetic fields at the micro Gauss level coherent on scales up to ten kpc. Recent observational evidence suggests that even the intergalactic medium in voids could host a weak  ∼  10(-16) Gauss magnetic field, coherent on Mpc scales. An intriguing possibility is that these observed magnetic fields are a relic from the early universe, albeit one which has been subsequently amplified and maintained by a dynamo in collapsed objects. We review here the origin, evolution and signatures of primordial magnetic fields. After a brief summary of magnetohydrodynamics in the expanding universe, we turn to magnetic field generation during inflation and phase transitions. We trace the linear and nonlinear evolution of the generated primordial fields through the radiation era, including viscous effects. Sensitive observational signatures of primordial magnetic fields on the cosmic microwave background, including current constraints from Planck, are discussed. After recombination, primordial magnetic fields could strongly influence structure formation, especially on dwarf galaxy scales. The resulting signatures on reionization, the redshifted 21 cm line, weak lensing and the Lyman-α forest are outlined. Constraints from radio and γ-ray astronomy are summarized. Astrophysical batteries and the role of dynamos in reshaping the primordial field are briefly considered. The review ends with some final thoughts on primordial magnetic fields.

Analysis of Gene Expression Profiles of Multiple Skin Diseases Identifies a Conserved Signature of Disrupted Homeostasis.

PubMed

Mills, Kevin J; Robinson, Michael K; Sherrill, Joseph D; Schnell, Daniel J; Xu, Jun

2018-05-28

Triggers of skin disease pathogenesis vary, but events associated with the elicitation of a lesion share many features in common. Our objective was to examine gene expression patterns in skin disease to develop a molecular signature of disruption of cutaneous homeostasis. Gene expression data from common inflammatory skin diseases (e.g., psoriasis, atopic dermatitis, seborrheic dermatitis and acne), and a novel statistical algorithm were used to define a unifying molecular signature referred to as the "Unhealthy Skin Signature" (USS). Using a pattern matching algorithm, analysis of public data repositories revealed that the USS is found in diverse epithelial diseases. Studies of milder disruptions of epidermal homeostasis have also shown that these conditions converge, to varying degrees, on the USS and that the degree of convergence is related directly to the severity of homeostatic disruption. The USS contains genes that had no prior published association with skin, but that play important roles in many different disease processes, supporting the importance of the USS to homeostasis. Finally, we show through pattern matching that the USS can be used to discover new potential dermatologic therapeutics. The USS provides a new means to further interrogate epithelial homeostasis and potentially develop novel therapeutics with efficacy across a spectrum of skin conditions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Oxidation and Hydration of U 3 O 8 Materials Following Controlled Exposure to Temperature and Humidity

DOE PAGES

Tamasi, Alison L.; Boland, Kevin S.; Czerwinski, Kenneth; ...

2015-03-18

Chemical signatures correlated with uranium oxide processing are of interest to forensic science for inferring sample provenance. Identification of temporal changes in chemical structures of process uranium materials as a function of controlled temperatures and relative humidities may provide additional information regarding sample history. In our study, a high-purity α-U 3O 8 sample and three other uranium oxide samples synthesized from reaction routes used in nuclear conversion processes were stored under controlled conditions over 2–3.5 years, and powder X-ray diffraction analysis and X-ray absorption spectroscopy were employed to characterize chemical speciation. We measured signatures from the α-U 3O 8 samplemore » indicated that the material oxidized and hydrated after storage under high humidity conditions over time. Impurities, such as uranyl fluoride or schoepites, were initially detectable in the other uranium oxide samples. After storage under controlled conditions, the analyses of the samples revealed oxidation over time, although the signature of the uranyl fluoride impurity diminished. The presence of schoepite phases in older uranium oxide material is likely indicative of storage under high humidity and should be taken into account for assessing sample history. Finally, the absence of a signature from a chemical impurity, such as uranyl fluoride hydrate, in an older material may not preclude its presence at the initial time of production. LA-UR-15-21495.« less

Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

PubMed Central

Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

2017-01-01

BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING. National Institutes of Health (CA154683, CA158557, CA177940, CA087497-13), Tisch Cancer Institute, Melanoma Research Foundation, the Dow Family Charitable Foundation, and the Icahn School of Medicine at Mount Sinai. PMID:28469092

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

PubMed Central

Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

2012-01-01

Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD. PMID:22393443

Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function

PubMed Central

Pasquini, L A; Millet, V; Hoyos, H C; Giannoni, J P; Croci, D O; Marder, M; Liu, F T; Rabinovich, G A; Pasquini, J M

2011-01-01

Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin–glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and -3 were abundant in astrocytes and microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose- and carbohydrate-dependent fashion consistent with the ‘glycosylation signature' of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3−/−) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3−/− compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3−/− mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3−/− mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3−/− mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders. PMID:21566659

An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease

PubMed Central

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

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow.

PubMed

Kulkarni, Shilpa; Koller, Antonius; Mani, Kartik M; Wen, Ruofeng; Alfieri, Alan; Saha, Subhrajit; Wang, Jian; Patel, Purvi; Bandeira, Nuno; Guha, Chandan; Chen, Emily I

2016-11-01

Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted proteins were identified in urinary and serum exosomes. Together, these data showed the feasibility of defining biomarkers that could elucidate tissue-associated and systemic response caused by high-dose ionizing radiation. This is the first report using an exosome proteomics approach to identify radiation signatures. Copyright © 2016 Elsevier Inc. All rights reserved.

Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma.

PubMed

Johnson, Jennifer; Ascierto, Maria Libera; Mittal, Sandeep; Newsome, David; Kang, Liang; Briggs, Michael; Tanner, Kirk; Marincola, Francesco M; Berens, Michael E; Vande Woude, George F; Xie, Qian

2015-09-17

Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM. Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p ≤ 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p ≤ 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p ≤ 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance. We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors. Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors. Human and mouse microarrays maybe used to dissect the tumor-host interactions. Targeting MET in EGFR (amp) GBM may delay the acquired resistance developed during treatment with erlotinib.

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulkarni, Shilpa; Koller, Antonius; Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York

Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24more » and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted proteins were identified in urinary and serum exosomes. Together, these data showed the feasibility of defining biomarkers that could elucidate tissue-associated and systemic response caused by high-dose ionizing radiation. This is the first report using an exosome proteomics approach to identify radiation signatures.« less

Development of a mixed seawater-hydrothermal fluid geochemical signature during alteration of volcanic rocks in the Archean (∼2.7 Ga) Abitibi Greenstone Belt, Canada

NASA Astrophysics Data System (ADS)

Brengman, Latisha A.; Fedo, Christopher M.

2018-04-01

We investigated a group of silicified volcanic rocks from the ∼2.72 Ga Hunter Mine Group (HMG), Abitibi Greenstone Belt, Canada, in order to document progressive compositional change associated with alteration in a subaqueous caldera system. Rocks of the HMG divide into three groups based on mineralogy and texture for petrographic and geochemical analyses. Volcanic features (phenocrysts, pseudomorphs after primary glass shards, lapilli, volcanic clasts) are preserved in all groups, despite changing mineralogy from primarily quartz, feldspar, chlorite (Groups 1 and 2), to quartz, hematite and carbonate (Groups 2 and 3). Compositionally, Group 1 rocks resemble volcanic rocks in the region, while Group 2 and 3 rocks show a change in mineralogy to iron, silica, and carbonate minerals, which is associated with depletion of many major and trace elements associated with volcanic rocks (Al2O3, Na2O, K2O, Zr). In addition, rare earth elements display a clear progression from volcanic signatures in Group 1 (PrSN/YbSN = 1.7-2.96, EuSN/EuSN∗ = 0.84-1.72, Y/Ho = 25.20-27.41, LaSN/LaSN∗ = 0.97-1.29, and Zr/Hf = 38.38-42.09) to transitional mixed volcanic, hydrothermal, and seawater signatures in Group 2 (PrSN/YbSN 1.33-2.89, EuSN/EuSN∗ 1.33-2.5, Y/Ho = 23.94-30, LaSN/LaSN∗ 0.93-1.34, and Zr/Hf = 40-70), to mixed hydrothermal and seawater signatures in Group 3 (PrSN/YbSN 0.62-2.88, EuSN/EuSN∗ 1.30-7.15, LaSN/LaSN∗ 1.02-1.86, Y/Ho = 25.56-55, and Zr/Hf = 35-50). We interpret that silicification of volcanic rocks (Group 1) produced transitional altered volcanic rocks (Group 2), and siliceous and jaspilitic rocks (Group 3), based on preservation of delicate volcanic features. Building on this explanation, we interpret that major, trace- and rare-earth element mobility occurred during the process of silicification, during which siliceous and jaspilitic rocks (Group 3) acquired aspects of the rare-earth element geochemical signatures of marine chemical precipitates. We conclude that seafloor silicification in hydrothermal depositional settings is capable of producing rocks that resemble marine chemical precipitates such as banded iron formation, and could be a process that is widespread in the Archean. Consequently, because silicified volcanic rocks from the HMG possess mixed seawater and hydrothermal rare-earth element characteristics similar to Archean iron formations and cherts, we suggest caution must be exercised when interpreting the geochemical information preserved in metamorphosed rocks where original genesis is unknown.

The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia.

PubMed

Simulundu, Edgar; Nao, Naganori; Yabe, John; Muto, Nilton A; Sithebe, Thami; Sawa, Hirofumi; Manzoor, Rashid; Kajihara, Masahiro; Muramatsu, Mieko; Ishii, Akihiro; Ogawa, Hirohito; Mweene, Aaron S; Takada, Ayato

2014-10-01

Whilst remarkable progress in elucidating the mechanisms governing interspecies transmission and pathogenicity of highly pathogenic avian influenza viruses (AIVs) has been made, similar studies focusing on low-pathogenic AIVs isolated from the wild waterfowl reservoir are limited. We previously reported that two AIV strains (subtypes H6N2 and H3N8) isolated from wild waterfowl in Zambia harbored some amino acid residues preferentially associated with human influenza virus proteins (so-called human signatures) and replicated better in the lungs of infected mice and caused more morbidity than a strain lacking such residues. To further substantiate these observations, we infected chickens and mice intranasally with AIV strains of various subtypes (H3N6, H3N8, H4N6, H6N2, H9N1 and H11N9) isolated from wild waterfowl in Zambia. Although some strains induced seroconversion, all of the tested strains replicated poorly and were nonpathogenic for chickens. In contrast, most of the strains having human signatures replicated well in the lungs of mice, and one of these strains caused severe illness in mice and induced lung injury that was characterized by a severe accumulation of polymorphonuclear leukocytes. These results suggest that some strains tested in this study may have the potential to infect mammalian hosts directly without adaptation, which might possibly be associated with the possession of human signature residues. Close monitoring and evaluation of host-associated signatures may help to elucidate the prevalence and emergence of AIVs with potential for causing zoonotic infections.

An immune-related lncRNA signature for patients with anaplastic gliomas.

PubMed

Wang, Wen; Zhao, Zheng; Yang, Fan; Wang, Haoyuan; Wu, Fan; Liang, Tingyu; Yan, Xiaoyan; Li, Jiye; Lan, Qing; Wang, Jiangfei; Zhao, Jizong

2018-01-01

We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937, AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in patients with anaplastic gliomas. Patients in the low-risk group showed longer overall survival (OS) and progression-free survival than those in the high-risk group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower Karnofsky performance score (KPS). Moreover, the signature was an independent factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR) = 1.434). These findings were further validated in two additional datasets (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune status based on principal components analysis. Our results showed that the nine immune-related lncRNAs signature has prognostic value for anaplastic gliomas.

Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

PubMed

Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

2018-04-01

We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation,we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and seven methylated DNAs from primary EOC tissues that predicted lymphatic invasion and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (p < 0.001 and p=0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (log-rank p-value=0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed and also associated with survival of EOC patients.

76 FR 10234 - Amendment to the Bank Secrecy Act Regulations-Reports of Foreign Financial Accounts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-24

...FinCEN is issuing this final rule to amend the Bank Secrecy Act (BSA) regulations regarding reports of foreign financial accounts. The rule addresses the scope of the persons that are required to file reports of foreign financial accounts. The rule further specifies the types of accounts that are reportable, and provides filing relief in the form of exemptions for certain persons with signature or other authority over foreign financial accounts. Finally, the rule adopts provisions intended to prevent persons subject to the rule from avoiding their reporting requirement.

Simulating supersymmetry at the SSC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnett, R.M.; Haber, H.E.

1984-08-01

Careful study of supersymmetric signatures at the SSC is required in order to distinguish them from Standard Model physics backgrounds. To this end, we have created an efficient, accurate computer program which simulates supersymmetric particle production and decay (or other new particles). We have incorporated the full matrix elements, keeping track of the polarizations of all intermediate states. (At this time hadronization of final-state partons is ignored). Using Monte Carlo techniques this program can generate any desired final-state distribution or individual events for Lego plots. Examples of the results of our study of supersymmetry at SSC are provided.

Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus.

PubMed

Cha, Jeeyeon; Burnum-Johnson, Kristin E; Bartos, Amanda; Li, Yingju; Baker, Erin S; Tilton, Susan C; Webb-Robertson, Bobbie-Jo M; Piehowski, Paul D; Monroe, Matthew E; Jegga, Anil G; Murata, Shigeo; Hirota, Yasushi; Dey, Sudhansu K

2015-06-12

Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses ("pseudoimplantation") that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Nearfield Summary and Statistical Analysis of the Second AIAA Sonic Boom Prediction Workshop

NASA Technical Reports Server (NTRS)

Park, Michael A.; Nemec, Marian

2017-01-01

A summary is provided for the Second AIAA Sonic Boom Workshop held 8-9 January 2017 in conjunction with AIAA SciTech 2017. The workshop used three required models of increasing complexity: an axisymmetric body, a wing body, and a complete configuration with flow-through nacelle. An optional complete configuration with propulsion boundary conditions is also provided. These models are designed with similar nearfield signatures to isolate geometry and shock/expansion interaction effects. Eleven international participant groups submitted nearfield signatures with forces, pitching moment, and iterative convergence norms. Statistics and grid convergence of these nearfield signatures are presented. These submissions are propagated to the ground, and noise levels are computed. This allows the grid convergence and the statistical distribution of a noise level to be computed. While progress is documented since the first workshop, improvement to the analysis methods for a possible subsequent workshop are provided. The complete configuration with flow-through nacelle showed the most dramatic improvement between the two workshops. The current workshop cases are more relevant to vehicles with lower loudness and have the potential for lower annoyance than the first workshop cases. The models for this workshop with quieter ground noise levels than the first workshop exposed weaknesses in analysis, particularly in convective discretization.

Application Of The Wigner-Ville Distribution To The Identification Of Machine Noise

NASA Astrophysics Data System (ADS)

Boashash, Boualem; O'Shea, Peter

1988-02-01

The theory of signal detection using the Wigner-Ville Distribution (WVD) and the Cross Wagner-Ville Distribution (XWVD) is reviewed, and applied to the signaturing, detection, and identification of some specific machine sounds - the individual cylinder firings of a marine engine. For this task, a 4 step procedure has been devised. The Autocorrelation Function (ACF) is first employed for ascertaining the number of engine cylinders and the firing rate of the engine. Cross-correlation techniques are then used for detecting the occurrence of cylinder firing events. This is followed by the use WVD and XWVD based analyses to produce high resolution Time-Frequency signatures, and finally 2D correlations are employed for identification of the cylinders. The proposed methodology is applied to real data.

Techniques for fire detection

NASA Technical Reports Server (NTRS)

Bukowski, Richard W.

1987-01-01

An overview is given of the basis for an analysis of combustable materials and potential ignition sources in a spacecraft. First, the burning process is discussed in terms of the production of the fire signatures normally associated with detection devices. These include convected and radiated thermal energy, particulates, and gases. Second, the transport processes associated with the movement of these from the fire to the detector, along with the important phenomena which cause the level of these signatures to be reduced, are described. Third, the operating characteristics of the individual types of detectors which influence their response to signals, are presented. Finally, vulnerability analysis using predictive fire modeling techniques is discussed as a means to establish the necessary response of the detection system to provide the level of protection required in the application.

Spectral signature verification using statistical analysis and text mining

NASA Astrophysics Data System (ADS)

DeCoster, Mallory E.; Firpi, Alexe H.; Jacobs, Samantha K.; Cone, Shelli R.; Tzeng, Nigel H.; Rodriguez, Benjamin M.

2016-05-01

In the spectral science community, numerous spectral signatures are stored in databases representative of many sample materials collected from a variety of spectrometers and spectroscopists. Due to the variety and variability of the spectra that comprise many spectral databases, it is necessary to establish a metric for validating the quality of spectral signatures. This has been an area of great discussion and debate in the spectral science community. This paper discusses a method that independently validates two different aspects of a spectral signature to arrive at a final qualitative assessment; the textual meta-data and numerical spectral data. Results associated with the spectral data stored in the Signature Database1 (SigDB) are proposed. The numerical data comprising a sample material's spectrum is validated based on statistical properties derived from an ideal population set. The quality of the test spectrum is ranked based on a spectral angle mapper (SAM) comparison to the mean spectrum derived from the population set. Additionally, the contextual data of a test spectrum is qualitatively analyzed using lexical analysis text mining. This technique analyzes to understand the syntax of the meta-data to provide local learning patterns and trends within the spectral data, indicative of the test spectrum's quality. Text mining applications have successfully been implemented for security2 (text encryption/decryption), biomedical3 , and marketing4 applications. The text mining lexical analysis algorithm is trained on the meta-data patterns of a subset of high and low quality spectra, in order to have a model to apply to the entire SigDB data set. The statistical and textual methods combine to assess the quality of a test spectrum existing in a database without the need of an expert user. This method has been compared to other validation methods accepted by the spectral science community, and has provided promising results when a baseline spectral signature is present for comparison. The spectral validation method proposed is described from a practical application and analytical perspective.

Major Sources of Organic Matter in a Complex Coral Reef Lagoon: Identification from Isotopic Signatures (δ13C and δ15N)

PubMed Central

Briand, Marine J.; Bonnet, Xavier; Goiran, Claire; Guillou, Gaël; Letourneur, Yves

2015-01-01

A wide investigation was conducted into the main organic matter (OM) sources supporting coral reef trophic networks in the lagoon of New Caledonia. Sampling included different reef locations (fringing, intermediate and barrier reef), different associated ecosystems (mangroves and seagrass beds) and rivers. In total, 30 taxa of macrophytes, plus pools of particulate and sedimentary OM (POM and SOM) were sampled. Isotopic signatures (C and N) of each OM sources was characterized and the composition of OM pools assessed. In addition, spatial and seasonal variations of reef OM sources were examined. Mangroves isotopic signatures were the most C-depleted (-30.17 ± 0.41 ‰) and seagrass signatures were the most C-enriched (-4.36 ± 0.72 ‰). Trichodesmium spp. had the most N-depleted signatures (-0.14 ± 0.03 ‰) whereas mangroves had the most N-enriched signatures (6.47 ± 0.41 ‰). The composition of POM and SOM varied along a coast-to-barrier reef gradient. River POM and marine POM contributed equally to coastal POM, whereas marine POM represented 90% of the POM on barrier reefs, compared to 10% river POM. The relative importance of river POM, marine POM and mangroves to the SOM pool decreased from fringing to barrier reefs. Conversely, the relative importance of seagrass, Trichodesmium spp. and macroalgae increased along this gradient. Overall, spatial fluctuations in POM and SOM were much greater than in primary producers. Seasonal fluctuations were low for all OM sources. Our results demonstrated that a large variety of OM sources sustain coral reefs, varying in their origin, composition and role and suggest that δ13C was a more useful fingerprint than δ15N in this endeavour. This study also suggested substantial OM exchanges and trophic connections between coral reefs and surrounding ecosystems. Finally, the importance of accounting for environmental characteristics at small temporal and spatial scales before drawing general patterns is highlighted. PMID:26134985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaffney, Jeffrey

This is the final technical report. The project description is as follows: to determine the role of aerosol radiative forcing on climate, the processes that control their atmospheric concentrations must be understood, and aerosol sources need to be determined for mitigation. Measurements of naturally occurring radionuclides and stable isotopic signatures allow the sources, removal and transport processes, as well as atmospheric lifetimes of fine carbonaceous aerosols, to be evaluated.

Utilization of Skylab EREP system for appraising changes in continental migratory bird habitat. [using multispectral band scanner

NASA Technical Reports Server (NTRS)

Gilmer, D. S. (Principal Investigator)

1975-01-01

The author has identified the following significant results. Surface water statistics using data obtained by supporting aircraft were generated. Signature extraction and refinement preliminary to wetland and associated upland vegetation recognition were accomplished, using a selected portion of the aircraft data. Final classification mapping and analysis of surface water trends will be accomplished.

Fully Adaptive Radar Modeling and Simulation Development

DTIC Science & Technology

2017-04-01

Graeme E . Smith The Ohio State University Bruce L. McKinley Signal Processing Consultants, Inc. APRIL 2017 Final Report THIS IS A...AIR FORCE MATERIEL COMMAND UNITED STATES AIR FORCE NOTICE AND SIGNATURE PAGE Using Government drawings, specifications, or other data ...formulated or supplied the drawings, specifications, or other data does not license the holder or any other person or corporation; or convey any

Nucleolar Reorganization Upon Site-Specific Double-Strand Break Induction

PubMed Central

Franek, Michal; Kovaříková, Alena; Bártová, Eva; Kozubek, Stanislav

2016-01-01

DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I-PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I-PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, γH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I-PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps. PMID:27680669

The challenges to inferring the regulators of biodiversity in deep time.

PubMed

Ezard, Thomas H G; Quental, Tiago B; Benton, Michael J

2016-04-05

Attempts to infer the ecological drivers of macroevolution in deep time have long drawn inspiration from work on extant systems, but long-term evolutionary and geological changes complicate the simple extrapolation of such theory. Recent efforts to incorporate a more informed ecology into macroevolution have moved beyond the descriptive, seeking to isolate generating mechanisms and produce testable hypotheses of how groups of organisms usurp each other or coexist over vast timespans. This theme issue aims to exemplify this progress, providing a series of case studies of how novel modelling approaches are helping infer the regulators of biodiversity in deep time. In this Introduction, we explore the challenges of these new approaches. First, we discuss how our choices of taxonomic units have implications for the conclusions drawn. Second, we emphasize the need to embrace the interdependence of biotic and abiotic changes, because no living organism ignores its environment. Third, in the light of parts 1 and 2, we discuss the set of dynamic signatures that we might expect to observe in the fossil record. Finally, we ask whether these dynamics represent the most ecologically informative foci for research efforts aimed at inferring the regulators of biodiversity in deep time. The papers in this theme issue contribute in each of these areas. © 2016 The Author(s).

Gene Expression Programs of Human Smooth Muscle Cells: Tissue-Specific Differentiation and Prognostic Significance in Breast Cancers

PubMed Central

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S. A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J.; Hastie, Trevor; Brown, Patrick O

2007-01-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression. PMID:17907811

Comparative analysis of protein interactome networks prioritizes candidate genes with cancer signatures.

PubMed

Li, Yongsheng; Sahni, Nidhi; Yi, Song

2016-11-29

Comprehensive understanding of human cancer mechanisms requires the identification of a thorough list of cancer-associated genes, which could serve as biomarkers for diagnoses and therapies in various types of cancer. Although substantial progress has been made in functional studies to uncover genes involved in cancer, these efforts are often time-consuming and costly. Therefore, it remains challenging to comprehensively identify cancer candidate genes. Network-based methods have accelerated this process through the analysis of complex molecular interactions in the cell. However, the extent to which various interactome networks can contribute to prediction of candidate genes responsible for cancer is still enigmatic. In this study, we evaluated different human protein-protein interactome networks and compared their application to cancer gene prioritization. Our results indicate that network analyses can increase the power to identify novel cancer genes. In particular, such predictive power can be enhanced with the use of unbiased systematic protein interaction maps for cancer gene prioritization. Functional analysis reveals that the top ranked genes from network predictions co-occur often with cancer-related terms in literature, and further, these candidate genes are indeed frequently mutated across cancers. Finally, our study suggests that integrating interactome networks with other omics datasets could provide novel insights into cancer-associated genes and underlying molecular mechanisms.

Open chromatin encoded in DNA sequence is the signature of ‘master’ replication origins in human cells

PubMed Central

Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain

2009-01-01

For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions ∼300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as ‘master’ replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these ‘master’ origins are likely to play a key role in genome dynamics during evolution and in pathological situations. PMID:19671527

c-Met–mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma

PubMed Central

Huang, Menggui; Liu, Tianrun; Ma, Peihong; Mitteer, R. Alan; Zhang, Zhenting; Kim, Hyun Jun; Yeo, Eujin; Zhang, Duo; Cai, Peiqiang; Li, Chunsheng; Zhang, Lin; Zhao, Botao; Roccograndi, Laura; O’Rourke, Donald M.; Dahmane, Nadia; Gong, Yanqing; Koumenis, Constantinos

2016-01-01

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase–14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor–derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors. PMID:27043280

Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.

PubMed

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J; Hastie, Trevor; Brown, Patrick O

2007-09-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression.

αβ T cell receptors as predictors of health and disease

PubMed Central

Attaf, Meriem; Huseby, Eric; Sewell, Andrew K

2015-01-01

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR ‘signatures' raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome. PMID:25619506

Epigenetic Disregulation in Oral Cancer

PubMed Central

Mascolo, Massimo; Siano, Maria; Ilardi, Gennaro; Russo, Daniela; Merolla, Francesco; De Rosa, Gaetano; Staibano, Stefania

2012-01-01

Squamous cell carcinoma of the oral region (OSCC) is one of the most common and highly aggressive malignancies worldwide, despite the fact that significant results have been achieved during the last decades in its detection, prevention and treatment. Although many efforts have been made to define the molecular signatures that identify the clinical outcome of oral cancers, OSCC still lacks reliable prognostic molecular markers. Scientific evidence indicates that transition from normal epithelium to pre-malignancy, and finally to oral carcinoma, depends on the accumulation of genetic and epigenetic alterations in a multistep process. Unlike genetic alterations, epigenetic changes are heritable and potentially reversible. The most common examples of such changes are DNA methylation, histone modification, and small non-coding RNAs. Although several epigenetic changes have been currently linked to OSCC initiation and progression, they have been only partially characterized. Over the last decade, it has been demonstrated that especially aberrant DNA methylation plays a critical role in oral cancer. The major goal of the present paper is to review the recent literature about the epigenetic modifications contribution in early and later phases of OSCC malignant transformation; in particular we point out the current evidence of epigenetic marks as novel markers for early diagnosis and prognosis as well as potential therapeutic targets in oral cancer. PMID:22408457

Indirect and Direct Signatures of Young Planets in Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Zhu, Zhaohuan; Stone, James M.; Dong, Ruobing; Rafikov, Roman; Bai, Xue-Ning

2015-12-01

Directly finding young planets around protostars is challenging since protostars are highly variable and obscured by dust. However, young planets will interact with protoplanetary disks, inducing disk features such as gaps, spiral arms, and asymmetric features, which are much easier to be detected. Transitional disks, which are protoplanetary disks with gaps and holes, are excellent candidates for finding young planets. Although these disks have been studied extensively in observations (e.g. using Subaru, VLT, ALMA, EVLA), theoretical models still need to be developed to explain observations. We have constructed numerical simulations, including dust particle dynamics and MHD effects, to study planet-disk interaction, with an emphasis on explaining observations. Our simulations have successfully reproduced spiral arms, gaps and asymmetric features observed in transitional disks. Furthermore, by comparing with observations, we have constrained protoplanetary disk properties and pinpoint potential planets in these disks. We will present progress in constructing global simulations to study transitional disks, including using our recently developed Athena++ code with static-mesh-refinement for MHD. Finally we suggest that accreting circumplanetary disks can release an observable amount of energy and could be the key to detect young planets directly. We will discuss how JWST and next generation telescopes can help to find these young planets with circumplanetary disks.

An Energy-Efficient Cluster-Based Vehicle Detection on Road Network Using Intention Numeration Method

PubMed Central

Devasenapathy, Deepa; Kannan, Kathiravan

2015-01-01

The traffic in the road network is progressively increasing at a greater extent. Good knowledge of network traffic can minimize congestions using information pertaining to road network obtained with the aid of communal callers, pavement detectors, and so on. Using these methods, low featured information is generated with respect to the user in the road network. Although the existing schemes obtain urban traffic information, they fail to calculate the energy drain rate of nodes and to locate equilibrium between the overhead and quality of the routing protocol that renders a great challenge. Thus, an energy-efficient cluster-based vehicle detection in road network using the intention numeration method (CVDRN-IN) is developed. Initially, sensor nodes that detect a vehicle are grouped into separate clusters. Further, we approximate the strength of the node drain rate for a cluster using polynomial regression function. In addition, the total node energy is estimated by taking the integral over the area. Finally, enhanced data aggregation is performed to reduce the amount of data transmission using digital signature tree. The experimental performance is evaluated with Dodgers loop sensor data set from UCI repository and the performance evaluation outperforms existing work on energy consumption, clustering efficiency, and node drain rate. PMID:25793221

An energy-efficient cluster-based vehicle detection on road network using intention numeration method.

PubMed

Devasenapathy, Deepa; Kannan, Kathiravan

2015-01-01

The traffic in the road network is progressively increasing at a greater extent. Good knowledge of network traffic can minimize congestions using information pertaining to road network obtained with the aid of communal callers, pavement detectors, and so on. Using these methods, low featured information is generated with respect to the user in the road network. Although the existing schemes obtain urban traffic information, they fail to calculate the energy drain rate of nodes and to locate equilibrium between the overhead and quality of the routing protocol that renders a great challenge. Thus, an energy-efficient cluster-based vehicle detection in road network using the intention numeration method (CVDRN-IN) is developed. Initially, sensor nodes that detect a vehicle are grouped into separate clusters. Further, we approximate the strength of the node drain rate for a cluster using polynomial regression function. In addition, the total node energy is estimated by taking the integral over the area. Finally, enhanced data aggregation is performed to reduce the amount of data transmission using digital signature tree. The experimental performance is evaluated with Dodgers loop sensor data set from UCI repository and the performance evaluation outperforms existing work on energy consumption, clustering efficiency, and node drain rate.

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

PubMed

Barnes, Virginia M; Kennedy, Adam D; Panagakos, Fotinos; Devizio, William; Trivedi, Harsh M; Jönsson, Thomas; Guo, Lining; Cervi, Shannon; Scannapieco, Frank A

2014-01-01

Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated with periodontal disease in diabetics. The metabolites identified in this study that discriminated the periodontal groups may be useful for developing diagnostics and therapeutics tailored to the diabetic population.

Global Metabolomic Analysis of Human Saliva and Plasma from Healthy and Diabetic Subjects, with and without Periodontal Disease

PubMed Central

Barnes, Virginia M.; Kennedy, Adam D.; Panagakos, Fotinos; Devizio, William; Trivedi, Harsh M.; Jönsson, Thomas; Guo, Lining; Cervi, Shannon; Scannapieco, Frank A.

2014-01-01

Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated with periodontal disease in diabetics. The metabolites identified in this study that discriminated the periodontal groups may be useful for developing diagnostics and therapeutics tailored to the diabetic population. PMID:25133529

Four-miRNA signature as a prognostic tool for lung adenocarcinoma.

PubMed

Lin, Yan; Lv, Yufeng; Liang, Rong; Yuan, Chunling; Zhang, Jinyan; He, Dan; Zheng, Xiaowen; Zhang, Jianfeng

2018-01-01

The aim of this study was to generate a novel miRNA expression signature to accurately predict prognosis for patients with lung adenocarcinoma (LUAD). Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple miRNAs with differential expression between LUAD and paired healthy tissues. We then evaluated the prognostic values of the differentially expressed miRNAs using univariate/multivariate Cox regression analysis. This analysis was ultimately used to construct a four-miRNA signature that effectively predicted patient survival. Finally, we analyzed potential functional roles of the target genes for these four miRNAs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Based on our cutoff criteria ( P <0.05 and |log2FC| >1.0), we identified a total of 187 differentially expressed miRNAs, including 148 that were upregulated in LUAD tissues and 39 that were downregulated. Four miRNAs (miR-148a-5p, miR-31-5p, miR-548v, and miR-550a-5p) were independently associated with survival based on Kaplan-Meier analysis. We generated a signature index based on the expression of these four miRNAs and stratified patients into low- and high-risk groups. Patients in the high-risk group had significantly shorter survival times than those in the low-risk group ( P =0.002). A functional enrichment analysis suggested that the target genes of these four miRNAs were involved in protein phosphorylation and the Hippo and sphingolipid signaling pathways. Taken together, our results suggest that our four-miRNA signature can be used as a prognostic tool for patients with LUAD.

Augmenting the impact of technology adoption with financial incentive to improve radiology report signature times.

PubMed

Andriole, Katherine P; Prevedello, Luciano M; Dufault, Allen; Pezeshk, Parham; Bransfield, Robert; Hanson, Richard; Doubilet, Peter M; Seltzer, Steven E; Khorasani, Ramin

2010-03-01

Radiology report signature time (ST) can be a substantial component of total report turnaround time. Poor turnaround time resulting from lengthy ST can adversely affect patient care. The combination of technology adoption with financial incentive was evaluated to determine if ST improvement can be augmented and sustained. This prospective study was performed at a 751-bed, urban, tertiary care adult teaching hospital. Test-site imaging volume approximated 48,000 examinations per month. The radiology department has 100 trainees and 124 attending radiologists serving multiple institutions. Over a study period of 4 years and 4 months, three interventions focused on radiologist signature performance were implemented: 1) a notification paging application that alerted radiologists when reports were ready for signature, 2) a picture archiving and communications systems (PACS)-integrated speech recognition report generation system, and 3) a departmental financial incentive to reward radiologists semiannually for ST performance. Signature time was compared before and after the interventions. Wilcoxon and linear regression statistical analyses were used to assess the significance of trends. Technology adoption (paging plus speech recognition) reduced median ST from >5 to <1 hour (P < .001) and 80th-percentile ST from >24 to 15 to 18 hours (P < .001). Subsequent addition of a financial incentive further improved 80th-percentile ST to 4 to 8 hours (P < .001). The gains in median and 80th-percentile ST were sustained over the final 31 months of the study period. Technology interventions coupled with financial incentive can result in synergistic and sustainable improvement in radiologist report-signing behavior. The addition of a financial incentive leads to better performance than that achievable through technology alone.

A two-step sensitivity analysis for hydrological signatures in Jinhua River Basin, East China

NASA Astrophysics Data System (ADS)

Pan, S.; Fu, G.; Chiang, Y. M.; Xu, Y. P.

2016-12-01

Owing to model complexity and large number of parameters, calibration and sensitivity analysis are difficult processes for distributed hydrological models. In this study, a two-step sensitivity analysis approach is proposed for analyzing the hydrological signatures in Jinhua River Basin, East China, using the Distributed Hydrology-Soil-Vegetation Model (DHSVM). A rough sensitivity analysis is firstly conducted to obtain preliminary influential parameters via Analysis of Variance. The number of parameters was greatly reduced from eighteen-three to sixteen. Afterwards, the sixteen parameters are further analyzed based on a variance-based global sensitivity analysis, i.e., Sobol's sensitivity analysis method, to achieve robust sensitivity rankings and parameter contributions. Parallel-Computing is applied to reduce computational burden in variance-based sensitivity analysis. The results reveal that only a few number of model parameters are significantly sensitive, including rain LAI multiplier, lateral conductivity, porosity, field capacity, wilting point of clay loam, understory monthly LAI, understory minimum resistance and root zone depths of croplands. Finally several hydrological signatures are used for investigating the performance of DHSVM. Results show that high value of efficiency criteria didn't indicate excellent performance of hydrological signatures. For most samples from Sobol's sensitivity analysis, water yield was simulated very well. However, lowest and maximum annual daily runoffs were underestimated. Most of seven-day minimum runoffs were overestimated. Nevertheless, good performances of the three signatures above still exist in a number of samples. Analysis of peak flow shows that small and medium floods are simulated perfectly while slight underestimations happen to large floods. The work in this study helps to further multi-objective calibration of DHSVM model and indicates where to improve the reliability and credibility of model simulation.

Measurement of microbial activity in soil by colorimetric observation of in situ dye reduction: an approach to detection of extraterrestrial life

PubMed Central

Crawford, Ronald L; Paszczynski, Andrzej; Lang, Qingyong; Erwin, Daniel P; Allenbach, Lisa; Corti, Giancarlo; Anderson, Tony J; Cheng, I Francis; Wai, Chien; Barnes, Bruce; Wells, Richard; Assefi, Touraj; Mojarradi, Mohammad

2002-01-01

Background Detecting microbial life in extraterrestrial locations is a goal of space exploration because of ecological and health concerns about possible contamination of other planets with earthly organisms, and vice versa. Previously we suggested a method for life detection based on the fact that living entities require a continual input of energy accessed through coupled oxidations and reductions (an electron transport chain). We demonstrated using earthly soils that the identification of extracted components of electron transport chains is useful for remote detection of a chemical signature of life. The instrument package developed used supercritical carbon dioxide for soil extraction, followed by chromatography or electrophoresis to separate extracted compounds, with final detection by voltammetry and tandem mass-spectrometry. Results Here we used Earth-derived soils to develop a related life detection system based on direct observation of a biological redox signature. We measured the ability of soil microbial communities to reduce artificial electron acceptors. Living organisms in pure culture and those naturally found in soil were shown to reduce 2,3-dichlorophenol indophenol (DCIP) and the tetrazolium dye 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT). Uninoculated or sterilized controls did not reduce the dyes. A soil from Antarctica that was determined by chemical signature and DNA analysis to be sterile also did not reduce the dyes. Conclusion Observation of dye reduction, supplemented with extraction and identification of only a few specific signature redox-active biochemicals such as porphyrins or quinones, provides a simplified means to detect a signature of life in the soils of other planets or their moons. PMID:12150716

All Paths Lead to TRIM25.

PubMed

Zhou, Hengbo; Costello, James C

2017-10-01

Identifying key factors that regulate the transition from primary to metastatic cancer is a fundamental challenge. Walsh et al. took a systems biology approach integrating computational, in vitro, and in vivo experiments to identify TRIM25 (tripartite motif containing 25) as a key factor that regulates metastatic gene signatures both at the transcriptional and post-transcriptional level in breast cancer. Targeting TRIM25 therapeutically is attractive because it governs a broad set of coordinated transcriptional modules that dictate metastatic progression. Copyright © 2017 Elsevier Inc. All rights reserved.

A Search for Extraterrestrial Amino Acids in Polar Ice: A Progress Report

NASA Technical Reports Server (NTRS)

Bada, Jeffrey L.; Brinton, Karen L. F.; McDonald, Gene D.; Wang, Xueyun

1996-01-01

Fifteen polar ice samples-fourteen from Greenland and one from Antarctica-have been analyzed for the extraterrestrial amino acid alpha-aminoisobutyric acid (AIB) in an effort to estimate the flux of interplanetary organic material to the Earth's surface. Only one sample (Greenland GISP II, 4270-4440 years old) contains detectable amounts of AIB, apparently the signature of a transient delivery event. The maximum oceanic concentration of AIB from such an event would be less than 10(exp-9) M.

CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. | Office of Cancer Genomics

Cancer.gov

Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumor suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer(NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behavior. Here we show that human KL cells and tumors share metabolic signatures of perturbed nitrogen handling.

The genesis and exodus of vascular plant DOM from an oak woodland landscape

NASA Astrophysics Data System (ADS)

Hernes, Peter J.; Spencer, Robert G. M.; Dyda, Rachael Y.; O'Geen, Anthony T.; Dahlgren, Randy A.

2017-02-01

Evaluating the collective impact of small source inputs to larger rivers is a constant challenge in riverine biogeochemistry. In this study, we investigated the generation of dissolved organic matter (DOM) in a small oak woodland catchment in the foothills of northern California, the subsequent transformation in lignin biomarkers and chromophoric DOM (CDOM) parameters during transport through the landscape to an exporting stream, and finally the overall compositional impact on the larger receiving stream and river. Our study included a natural leaching experiment in which precipitation passing through oak, pine, and grass litter and duff samples was collected after each of a series of storms. Also included were soil trench samples to capture subsurface flow, stream samples along with point-source reservoir inputs, and samples of canopy throughfall, stemflow, and gopher hole (bypass) flow. The litter/duff leaching study demonstrated changing DOM fractionation patterns throughout the season, as evidenced by changing lignin compositions in the leachates with each successive storm. This adds a necessary seasonal component to interpreting lignin compositions in streams, as the source signatures are constantly changing. Released DOM from leaching was modified extensively during transit through the subsurface to the stream, with preferential increases in aromaticity as evidenced by increases in carbon-normalized absorbance at 254 nm, yet preferential decreases in lignin phenols, as evidence by carbon-normalized lignin yields in the headwater stream that was less than half that of the litter/duff leachates. Our extensive number of lignin measurements for source materials reveals a much more complex perspective on using lignin as a source indicator, as many riverine values for syringyl:vanillyl and cinnamyl:vanillyl ratios that have previously been interpreted as degraded lignin signatures are also possible as unmodified source signatures. Finally, this study demonstrated that the impact of numerous small headwater streams can significantly overprint the DOM signatures of much larger rivers over relatively short distances spanning several to tens of kilometers. This finding in particular challenges the assumption that river studies can be adequately conducted by focusing only on the main tributaries.

Validation of a Radiosensitivity Molecular Signature in Breast Cancer

PubMed Central

Eschrich, Steven A.; Fulp, William J.; Pawitan, Yudi; Foekens, John A.; Smid, Marcel; Martens, John W. M.; Echevarria, Michelle; Kamath, Vidya; Lee, Ji-Hyun; Harris, Eleanor E.; Bergh, Jonas; Torres-Roca, Javier F.

2014-01-01

Purpose Previously, we developed a radiosensitivity molecular signature (RSI) that was clinically-validated in three independent datasets (rectal, esophageal, head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT) treated breast cancer patients. Experimental Design RSI was tested in two previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n=159) and Erasmus Medical Center (n=344). RSI was applied as previously described. Results We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5 yr relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, p=0.0212) but there was no difference between RS/RR patients treated without RT (71% vs. 77%, p=0.6744), consistent with RSI being RT-specific (interaction term RSIxRT, p=0.05). Similarly, in the Erasmus dataset RT-treated RS patients had an improved 5-year distant-metastasis-free survival over RR patients (77% vs. 64%, p=0.0409) but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, p=0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR=5.53, p=0.0987, Erasmus, HR=1.64, p=0.0758) and in backward selection (removal alpha of 0.10) RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR=2.64, p=0.0085). Conclusions RSI is validated in two independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in five independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. PMID:22832933

Epigenetics and Cellular Metabolism

PubMed Central

Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy

PubMed Central

Kong, Xiangju; Hong, Aayoung; Koya, Richard C.; Moriceau, Gatien; Chodon, Thinle; Guo, Rongqing; Johnson, Douglas B.; Dahlman, Kimberly B.; Kelley, Mark C.; Kefford, Richard F.; Chmielowski, Bartosz; Glaspy, John A.; Sosman, Jeffrey A.; van Baren, Nicolas; Long, Georgina V.; Ribas, Antoni; Lo, Roger S.

2013-01-01

BRAF inhibitors elicit rapid anti-tumor responses in the majority of patients with V600BRAF mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that MAPK reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification and alternative splicing being most common. We also detected PI3K-PTEN-AKT-upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions, in both core drug escape pathways, were commonly detected concurrently in the same tumor or among multiple tumors from the same patient. Beyond harboring extensively heterogeneous resistance mechanisms, melanoma re-growth emerging from BRAF inhibitor selection displayed branched evolution marked by altered mutational spectra/signatures and increased fitness. Thus, melanoma genomic heterogeneity contributes significantly to BRAF inhibitor treatment failure, implying upfront, co-targeting of two core pathways as an essential strategy for durable responses. PMID:24265155

Small nucleolar RNA U2_19 promotes hepatocellular carcinoma progression by regulating Wnt/β-catenin signaling.

PubMed

Wang, Haitao; Ma, Pei; Liu, Pengpeng; Chen, Baiyang; Liu, Zhisu

2018-06-02

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in oncogenesis. In the present study, we investigated the role of box C/D small nucleolar RNA U2_19 (snoU2_19) in the tumorigenesis of hepatocellular carcinoma (HCC). Recently, we screened snoRNAs differential signatures by performing high-throughput small RNA sequence in HCC tissues and validated that upregulated snoU2_19 was associated with aggressive phenotypes in HCC patients. Aberrant snoU2_19 facilitated HCC cell proliferation, inhibited apoptosis and induced cell cycle progression in vitro analyses. We globally investigated the molecular mechanisms of snoU2_19 in HCC and found that snoU2_19 knockdown inhibited Wnt/β-catenin signaling pathway through inducing the translocation of β-catenin in cytoplasm. We concluded that snoU2_19 plays a pathological role in the development and progression of HCC, and is a potential therapeutic target for HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Biomass power for rural development. Technical progress report, May 1, 1996--December 31, 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

Developing commercial energy crops for power generation by the year 2000 is the focus of the DOE/USDA sponsored Biomass Power for Rural Development project. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-I, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Facette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG). Phase-II of the project willmore » focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. There will be testing of the energy crop as part of the gasification trials expected to occur at BED`s McNeill power station and potentially at one of GPU`s facilities. Phase-III will represent full-scale commercialization of the energy crop and power generation on a sustainable basis. Willow has been selected as the energy crop of choice for many reasons. Willow is well suited to the climate of the Northeastern United States, and initial field trials have demonstrated that the yields required for the success of the project are obtainable. Like other energy crops, willow has rural development benefits and could serve to diversify local crop production, provide new sources of income for participating growers, and create new jobs. Willow could be used to put a large base of idle acreage back into crop production. Additionally, the willow coppicing system integrates well with current farm operations and utilizes agricultural practices that are already familiar to farmers.« less

Biomass power for rural development. Technical progress report, July 1--September 30, 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuhauser, E.

The focus of the DOE/USDA sponsored biomass power for rural development project is to develop commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC).more » Phase-2 of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is underway. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-3 will represent fullscale commercialization of the energy crop and power generation on a sustainable basis. During the third quarter of 1997, much of the Consortium`s effort has focused on outreach activities, continued feedstock development, fuel supply planning, and fuel contract development, and preparation for 1998 scale-up activities. The Consortium also submitted a Phase-1 extension proposal during this period. A few of the more important milestones are outlined below. The fourth quarter of 1997 is expected to be dominated by Phase-II proposal efforts and planning for 1998 activities.« less

Implementing traceability using particle randomness-based textile printed tags

NASA Astrophysics Data System (ADS)

Agrawal, T. K.; Koehl, L.; Campagne, C.

2017-10-01

This article introduces a random particle-based traceability tag for textiles. The proposed tag not only act as a unique signature for the corresponding textile product but also possess the features such as easy to manufacture and hard to copy. It seeks applications in brand authentication and traceability in textile and clothing (T&C) supply chain. A prototype has been developed by screen printing process, in which micron-scale particles were mixed with the printing paste and printed on cotton fabrics to attain required randomness. To encode the randomness, the image of the developed tag was taken and analyzed using image processing. The randomness of the particles acts as a product key or unique signature which is required to decode the tag. Finally, washing and abrasion resistance tests were conducted to check the durability of the printed tag.

Signature-based search for delayed photons in exclusive photon plus missing transverse energy events from pp¯ collisions with s=1.96TeV

NASA Astrophysics Data System (ADS)

Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Ciocci, M. A.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d'Ascenzo, N.; Datta, M.; De Barbaro, P.; Demortier, L.; Deninno, M.; d'Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; D'Onofrio, M.; Donati, S.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Eusebi, R.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grinstein, S.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. B.; Kim, S. H.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucà, A.; Lucchesi, D.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Margaroli, F.; Marino, P.; Martínez, M.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Ranjan, N.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sinervo, P.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; Stancari, M.; Denis, R. St.; Stelzer, B.; Stelzer-Chilton, O.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Warburton, A.; Waters, D.; Wester, W. C., III; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W.-M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

2013-08-01

We present the first signature-based search for delayed photons using an exclusive photon plus missing transverse energy final state. Events are reconstructed in a data sample from the CDF II detector corresponding to 6.3fb-1 of integrated luminosity from s=1.96TeV proton-antiproton collisions. Candidate events are selected if they contain a photon with an arrival time in the detector larger than expected from a promptly produced photon. The mean number of events from standard model sources predicted by the data-driven background model based on the photon timing distribution is 286±24. A total of 322 events are observed. A p value of 12% is obtained, showing consistency of the data with standard model predictions.

A Robust Blind Quantum Copyright Protection Method for Colored Images Based on Owner's Signature

NASA Astrophysics Data System (ADS)

Heidari, Shahrokh; Gheibi, Reza; Houshmand, Monireh; Nagata, Koji

2017-08-01

Watermarking is the imperceptible embedding of watermark bits into multimedia data in order to use for different applications. Among all its applications, copyright protection is the most prominent usage which conceals information about the owner in the carrier, so as to prohibit others from assertion copyright. This application requires high level of robustness. In this paper, a new blind quantum copyright protection method based on owners's signature in RGB images is proposed. The method utilizes one of the RGB channels as indicator and two remained channels are used for embedding information about the owner. In our contribution the owner's signature is considered as a text. Therefore, in order to embed in colored image as watermark, a new quantum representation of text based on ASCII character set is offered. Experimental results which are analyzed in MATLAB environment, exhibit that the presented scheme shows good performance against attacks and can be used to find out who the real owner is. Finally, the discussed quantum copyright protection method is compared with a related work that our analysis confirm that the presented scheme is more secure and applicable than the previous ones currently found in the literature.

A Neural Signature Encoding Decisions under Perceptual Ambiguity

PubMed Central

Sun, Sai; Yu, Rongjun

2017-01-01

Abstract People often make perceptual decisions with ambiguous information, but it remains unclear whether the brain has a common neural substrate that encodes various forms of perceptual ambiguity. Here, we used three types of perceptually ambiguous stimuli as well as task instructions to examine the neural basis for both stimulus-driven and task-driven perceptual ambiguity. We identified a neural signature, the late positive potential (LPP), that encoded a general form of stimulus-driven perceptual ambiguity. In addition to stimulus-driven ambiguity, the LPP was also modulated by ambiguity in task instructions. To further specify the functional role of the LPP and elucidate the relationship between stimulus ambiguity, behavioral response, and the LPP, we employed regression models and found that the LPP was specifically associated with response latency and confidence rating, suggesting that the LPP encoded decisions under perceptual ambiguity. Finally, direct behavioral ratings of stimulus and task ambiguity confirmed our neurophysiological findings, which could not be attributed to differences in eye movements either. Together, our findings argue for a common neural signature that encodes decisions under perceptual ambiguity but is subject to the modulation of task ambiguity. Our results represent an essential first step toward a complete neural understanding of human perceptual decision making. PMID:29177189

Encountering bird alarms in full-stare IRSTs

NASA Astrophysics Data System (ADS)

de Jong, Arie N.; Winkel, Hans; Kemp, Rob A. W.

2000-12-01

Birds are a potential source of frequent false alarms in Infrared Search and Track (IRST) systems. One reason is that the signals, generated by birds at short ranges (1-2 km) in IR sensors may be of the same magnitude as the signals generated by real targets (missiles) at long ranges (10-20 km). Another reason is that new generations of IRSTs have more sensitivity which brings more birds within the detection range. Furthermore military operations tend to be held more and more in coastal zones, where the frequency of occurrence of birds is greater than in the open ocean. Finally, the variety in type of birds and their flight characteristics and signature is larger. In the paper attention is spent on the IR signatures of birds in various backgrounds, including rapid variations in signature due to wing motions. Basically, these fluctuations and the flight pattern of a bird provide opportunities to encounter bird alarms in next generation IRSTs, using multiple Focal Plan Array cameras with high frame rates. One has to take into account in this process the difference between signal variations due to wing motions and scintillation for long range targets above the horizon.

Molecular signatures of fossil leaves provide unexpected new evidence for extinct plant relationships.

PubMed

Vajda, Vivi; Pucetaite, Milda; McLoughlin, Stephen; Engdahl, Anders; Heimdal, Jimmy; Uvdal, Per

2017-08-01

Gene sequences form the primary basis for understanding the relationships among extant plant groups, but genetic data are unavailable from fossils to evaluate the affinities of extinct taxa. Here we show that geothermally resistant fossil cuticles of seed-bearing plants, analysed with Fourier transform infrared (FTIR) spectroscopy and hierarchical cluster analysis (HCA), retain biomolecular suites that consistently distinguish major taxa even after experiencing different diagenetic histories. Our results reveal that similarities between the cuticular biochemical signatures of major plant groups (extant and fossil) are mostly consistent with recent phylogenetic hypotheses based on molecular and morphological data. Our novel chemotaxonomic data also support the hypothesis that the extinct Nilssoniales and Bennettitales are closely allied, but only distantly related to Cycadales. The chemical signature of the cuticle of Czekanowskia (Leptostrobales) is strongly similar to that of Ginkgo leaves and supports a close evolutionary relationship between these groups. Finally, our results also reveal that the extinct putative araucariacean, Allocladus, when analysed through HCA, is grouped closer to Ginkgoales than to conifers. Thus, in the absence of modern relatives yielding molecular information, FTIR spectroscopy provides valuable proxy biochemical data complementing morphological characters to distinguish fossil taxa and to help elucidate extinct plant relationships.

Ground-based sensors for the SR-71 sonic boom propagation experiment

NASA Technical Reports Server (NTRS)

Norris, Stephen R.; Haering, Edward A., Jr.; Murray, James E.

1995-01-01

This paper describes ground-level measurements of sonic boom signatures made as part of the SR-71 sonic boom propagation experiment recently completed at NASA Dryden Flight Research Center, Edwards, California. Ground level measurements were the final stage of this experiment which also included airborne measurements at near and intermediate distances from an SR-71 research aircraft. Three types of sensors were deployed to three station locations near the aircraft ground track. Pressure data were collected for flight conditions from Mach 1.25 to Mach 1.60 at altitudes from 30,000 to 48,000 ft. Ground-level measurement techniques, comparisons of data sets from different ground sensors, and sensor system strengths and weaknesses are discussed. The well-known N-wave structure dominated the sonic boom signatures generated by the SR-71 aircraft at most of these conditions. Variations in boom shape caused by atmospheric turbulence, focusing effects, or both were observed for several flights. Peak pressure and boom event duration showed some dependence on aircraft gross weight. The sonic boom signatures collected in this experiment are being compiled in a data base for distribution in support of the High Speed Research Program.

Hardware test program for evaluation of baseline range/range rate sensor concept

NASA Technical Reports Server (NTRS)

Pernic, E.

1985-01-01

The test program Phase II effort provides additional design information in terms of range and range rate (R/R) sensor performance when observing and tracking a typical spacecraft target. The target used in the test program was a one-third scale model of the Hubble Space Telescope (HST) available at the MSFC test site where the tests were performed. A modified Bendix millimeter wave radar served as the R/R sensor test bed for evaluation of range and range rate tracking performance, and generation of radar signature characteristics of the spacecraft target. A summary of program test results and conclusions are presented along with detailed description of the Bendix test bed radar with accompaning instrumentation. The MSFC test site and facilities are described. The test procedures used to establish background levels, and the calibration procedures used in the range accuracy tests and RCS (radar cross section) signature measurements, are presented and a condensed version of the daily log kept during the 5 September through 17 September test period is also presented. The test program results are given starting with the RCS signature measurements, then continuing with range measurement accuracy test results and finally the range and range rate tracking accuracy test results.

A Neural Signature Encoding Decisions under Perceptual Ambiguity.

PubMed

Sun, Sai; Yu, Rongjun; Wang, Shuo

2017-01-01

People often make perceptual decisions with ambiguous information, but it remains unclear whether the brain has a common neural substrate that encodes various forms of perceptual ambiguity. Here, we used three types of perceptually ambiguous stimuli as well as task instructions to examine the neural basis for both stimulus-driven and task-driven perceptual ambiguity. We identified a neural signature, the late positive potential (LPP), that encoded a general form of stimulus-driven perceptual ambiguity. In addition to stimulus-driven ambiguity, the LPP was also modulated by ambiguity in task instructions. To further specify the functional role of the LPP and elucidate the relationship between stimulus ambiguity, behavioral response, and the LPP, we employed regression models and found that the LPP was specifically associated with response latency and confidence rating, suggesting that the LPP encoded decisions under perceptual ambiguity. Finally, direct behavioral ratings of stimulus and task ambiguity confirmed our neurophysiological findings, which could not be attributed to differences in eye movements either. Together, our findings argue for a common neural signature that encodes decisions under perceptual ambiguity but is subject to the modulation of task ambiguity. Our results represent an essential first step toward a complete neural understanding of human perceptual decision making.

Resonance-Based Time-Frequency Manifold for Feature Extraction of Ship-Radiated Noise.

PubMed

Yan, Jiaquan; Sun, Haixin; Chen, Hailan; Junejo, Naveed Ur Rehman; Cheng, En

2018-03-22

In this paper, a novel time-frequency signature using resonance-based sparse signal decomposition (RSSD), phase space reconstruction (PSR), time-frequency distribution (TFD) and manifold learning is proposed for feature extraction of ship-radiated noise, which is called resonance-based time-frequency manifold (RTFM). This is suitable for analyzing signals with oscillatory, non-stationary and non-linear characteristics in a situation of serious noise pollution. Unlike the traditional methods which are sensitive to noise and just consider one side of oscillatory, non-stationary and non-linear characteristics, the proposed RTFM can provide the intact feature signature of all these characteristics in the form of a time-frequency signature by the following steps: first, RSSD is employed on the raw signal to extract the high-oscillatory component and abandon the low-oscillatory component. Second, PSR is performed on the high-oscillatory component to map the one-dimensional signal to the high-dimensional phase space. Third, TFD is employed to reveal non-stationary information in the phase space. Finally, manifold learning is applied to the TFDs to fetch the intrinsic non-linear manifold. A proportional addition of the top two RTFMs is adopted to produce the improved RTFM signature. All of the case studies are validated on real audio recordings of ship-radiated noise. Case studies of ship-radiated noise on different datasets and various degrees of noise pollution manifest the effectiveness and robustness of the proposed method.

Resonance-Based Time-Frequency Manifold for Feature Extraction of Ship-Radiated Noise

PubMed Central

Yan, Jiaquan; Sun, Haixin; Chen, Hailan; Junejo, Naveed Ur Rehman; Cheng, En

2018-01-01

In this paper, a novel time-frequency signature using resonance-based sparse signal decomposition (RSSD), phase space reconstruction (PSR), time-frequency distribution (TFD) and manifold learning is proposed for feature extraction of ship-radiated noise, which is called resonance-based time-frequency manifold (RTFM). This is suitable for analyzing signals with oscillatory, non-stationary and non-linear characteristics in a situation of serious noise pollution. Unlike the traditional methods which are sensitive to noise and just consider one side of oscillatory, non-stationary and non-linear characteristics, the proposed RTFM can provide the intact feature signature of all these characteristics in the form of a time-frequency signature by the following steps: first, RSSD is employed on the raw signal to extract the high-oscillatory component and abandon the low-oscillatory component. Second, PSR is performed on the high-oscillatory component to map the one-dimensional signal to the high-dimensional phase space. Third, TFD is employed to reveal non-stationary information in the phase space. Finally, manifold learning is applied to the TFDs to fetch the intrinsic non-linear manifold. A proportional addition of the top two RTFMs is adopted to produce the improved RTFM signature. All of the case studies are validated on real audio recordings of ship-radiated noise. Case studies of ship-radiated noise on different datasets and various degrees of noise pollution manifest the effectiveness and robustness of the proposed method. PMID:29565288

Population genomics of the honey bee reveals strong signatures of positive selection on worker traits.

PubMed

Harpur, Brock A; Kent, Clement F; Molodtsova, Daria; Lebon, Jonathan M D; Alqarni, Abdulaziz S; Owayss, Ayman A; Zayed, Amro

2014-02-18

Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees.

Population genomics of the honey bee reveals strong signatures of positive selection on worker traits

PubMed Central

Harpur, Brock A.; Kent, Clement F.; Molodtsova, Daria; Lebon, Jonathan M. D.; Alqarni, Abdulaziz S.; Owayss, Ayman A.; Zayed, Amro

2014-01-01

Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis-specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis-regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees. PMID:24488971

Temporal Variations in the Mantle Source of MORB near the Vema Fracture Zone (Central Atlantic): Nd and Sr Isotopes in Peridotites and Basaltic Glasses

NASA Astrophysics Data System (ADS)

Cipriani, A.; Cipriani, A.; Brunelli, D.; Brueckner, H. K.; Brueckner, H. K.; Bonatti, E.; Bonatti, E.

2001-12-01

Sr-Nd-Pb isotopic ratios of zero age basalts sampled along Mid-Ocean Ridges (MOR) have demonstrated that the mantle is heterogeneous at a regional scale. However, how the mantle evolves through time below a single segment of MOR it is still matter of debate. Peridotites and basaltic glasses were collected along a lithospheric section uplifted and exposed on the southern side of the Vema transform (10o North, Atlantic Ocean) along a seafloor spreading flow line for a stretch of almost 200 km (corresponding to roughly 10 my). This set of samples offers a unique opportunity to detect changes through time of the mantle signature in a segment of Mid Atlantic Ridge, by analyzing radiogenic isotopes in the clinopyroxenes (cpx) from peridotites and glasses from the overlying basalts. Work is in progress; initial Sr and Nd measurements from cpxs within peridotites indicate several things. First, the cpxs display "depleted" mantle signatures. Second, there is a considerable variation of the isotopic ratios along the exposed section (143Nd/144Nd varies from 0.51293 to 0.51345, 87Sr/86Sr varies from 0.70228 to 0.70422) and these variations occur over a short time scale (some occur within an interval of one million year). Next, the Sr and Nd ratios are inversely correlated and fall along the mantle array. Finally, cpx Nd ratios are inversely correlated with the Cr/Al ratio of the spinel and ortopyroxene (opx) from the peridotites while Sr ratios are positively correlated. Thus, the chemically most depleted peridotite with high Cr/Al ratios show the most enriched isotopic signatures, a pattern that has also been observed in alpine-type peridotites and peridotite nodules and that is generally interpreted as metasomatism by enriched fluids affecting depleted peridotite more extensively than less depleted peridotite. This may indicate that the temporal variations in the extent of melting detected by Cr/Al ratio in spinel and opx (Bonatti et al., Variations with age of mantle ultramafic composition near the Vema Fracture Zone, Central Atlantic. EOS, Vol.79, No.45, F919) are related to rapid changes in the degree of depletion of the upwelling mantle sources and that the degree of depletion of these mantle sources is an inherited feature from earlier processes rather than the result of melting at the MOR.

Visualization of genome signatures of eukaryote genomes by batch-learning self-organizing map with a special emphasis on Drosophila genomes.

PubMed

Abe, Takashi; Hamano, Yuta; Ikemura, Toshimichi

2014-01-01

A strategy of evolutionary studies that can compare vast numbers of genome sequences is becoming increasingly important with the remarkable progress of high-throughput DNA sequencing methods. We previously established a sequence alignment-free clustering method "BLSOM" for di-, tri-, and tetranucleotide compositions in genome sequences, which can characterize sequence characteristics (genome signatures) of a wide range of species. In the present study, we generated BLSOMs for tetra- and pentanucleotide compositions in approximately one million sequence fragments derived from 101 eukaryotes, for which almost complete genome sequences were available. BLSOM recognized phylotype-specific characteristics (e.g., key combinations of oligonucleotide frequencies) in the genome sequences, permitting phylotype-specific clustering of the sequences without any information regarding the species. In our detailed examination of 12 Drosophila species, the correlation between their phylogenetic classification and the classification on the BLSOMs was observed to visualize oligonucleotides diagnostic for species-specific clustering.

The coupling technique: A two-wave acoustic method for the study of dislocation dynamics

NASA Astrophysics Data System (ADS)

Gremaud, G.; Bujard, M.; Benoit, W.

1987-03-01

Progress in the study of dislocation dynamics has been achieved using a two-wave acoustic method, which has been called the coupling technique. In this method, the attenuation α and the velocity v of ultrasonic waves are measured in a sample submitted simultaneously to a harmonic stress σ of low frequency. Closed curves Δα(σ) and Δv/v(σ) are drawn during each cycle of the applied stress. The shapes of these curves and their evolution are characteristic of each dislocation motion mechanism which is activated by the low-frequency applied stress. For this reason, the closed curves Δα(σ) and Δv/v(σ) can be considered as signatures of the interaction mechanism which controls the low-frequency dislocation motion. In this paper, the concept of signature is presented and explained with some experimental examples. It will also be shown that theoretical models can be developed which explain very well the experimental results.

Nanophysics in graphene: neutrino physics in quantum rings and superlattices.

PubMed

Fertig, H A; Brey, Luis

2010-12-13

Electrons in graphene at low energy obey a two-dimensional Dirac equation, closely analogous to that of neutrinos. As a result, quantum mechanical effects when the system is confined or subjected to potentials at the nanoscale may be quite different from what happens in conventional electronic systems. In this article, we review recent progress on two systems where this is indeed the case: quantum rings and graphene electrons in a superlattice potential. In the former case, we demonstrate that the spectrum reveals signatures of 'effective time-reversal symmetry breaking', in which the spectra are most naturally interpreted in terms of effective magnetic flux contained in the ring, even when no real flux is present. A one-dimensional superlattice potential is shown to induce strong band-structure changes, allowing the number of Dirac points at zero energy to be manipulated by the strength and/or period of the potential. The emergence of new Dirac points is shown to be accompanied by strong signatures in the conduction properties of the system.

Rydberg phases of Hydrogen and low energy nuclear reactions

NASA Astrophysics Data System (ADS)

Olafsson, Sveinn; Holmlid, Leif

2016-03-01

For over the last 26 years the science of cold fusion/LENR has been researched around the world with slow pace of progress. Modest quantity of excess heat and signatures of nuclear transmutation and helium production have been confirmed in experiments and theoretical work has only resulted in a large flora of inadequate theoretical scenarios. Here we review current state of research in Rydberg matter of Hydrogen that is showing strong signature of nuclear processes. In the presentation experimental behavior of Rydberg matter of hydrogen is described. An extensive collaboration effort of surface physics, catalysis, atomic physics, solid state physics, nuclear physics and quantum information is need to tackle the surprising experimental results that have so far been obtained. Rydberg matter of Hydrogen is the only known state of matter that is able to bring huge collection of protons to so short distances and for so long time that tunneling becomes a reasonable process for making low energy nuclear reactions. Nuclear quantum entanglement can also become realistic process at theses conditions.

Toward the Responsible Development and Commercialization of Sensor Nanotechnologies.

PubMed

Fadel, Tarek R; Farrell, Dorothy F; Friedersdorf, Lisa E; Griep, Mark H; Hoover, Mark D; Meador, Michael A; Meyyappan, M

2016-01-01

Nanotechnology-enabled sensors (or nanosensors) will play an important role in enabling the progression toward ubiquitous information systems as the Internet of Things (IoT) emerges. Nanosensors offer new, miniaturized solutions in physiochemical and biological sensing that enable increased sensitivity, specificity, and multiplexing capability, all with the compelling economic drivers of low cost and high-energy efficiency. In the United States, Federal agencies participating in the National Nanotechnology Initiative (NNI) "Nanotechnology for Sensors and Sensors for Nanotechnology: Improving and Protecting Health, Safety, and the Environment" Nanotechnology Signature Initiative (the Sensors NSI), address both the opportunity of using nanotechnology to advance sensor development and the challenges of developing sensors to keep pace with the increasingly widespread use of engineered nanomaterials. This perspective article will introduce and provide background on the NNI signature initiative on sensors. Recent efforts by the Sensors NSI aimed at promoting the successful development and commercialization of nanosensors will be reviewed and examples of sensor nanotechnologies will be highlighted. Future directions and critical challenges for sensor development will also be discussed.

Magnetic field influence on the proximity effect at YB a2C u3O7/L a2 /3C a1 /3Mn O3 superconductor/half-metal interfaces

NASA Astrophysics Data System (ADS)

Visani, C.; Cuellar, F.; Pérez-Muñoz, A.; Sefrioui, Z.; León, C.; Santamaría, J.; Villegas, Javier E.

2015-07-01

We experimentally study the superconducting proximity effect in high-temperature superconductor/half-metallic ferromagnet YB a2C u3O7/L a2 /3C a1 /3Mn O3 junctions, using conductance measurements. In particular, we investigate the magnetic-field dependence of the spectroscopic signatures that evidence the long-range penetration of superconducting correlations into the half-metal. Those signatures are insensitive to the applied field when this is below the ferromagnet's saturation fields, which demonstrates that they are uncorrelated with its macroscopic magnetization. However, the application of more intense fields progressively washes away the fingerprint of long-range proximity effects. This is consistent with the fact that the well-known magnetic inhomogeneities at the c -axis YB a2C u3O7/L a2 /3C a1 /3Mn O3 interface play a role in the proximity behavior.

Results on top-quark physics and top-quark-like signatures by CMS

NASA Astrophysics Data System (ADS)

Chabert, Eric; CMS Collaboration

2017-07-01

This report reviews the results obtained by the CMS Collaboration on top quark physics, focusing on the latest ones based on p-p collisions provided by the LHC at \\sqrt{s}=13{{TeV}} during Run II. It covers measurements of single-top, top quark pairs and associated productions as well as measurements of top quark properties. Finally several beyond the standard model searches involving top quark in the final states are presented, such as searches for supersymmetry in the third generation, heavy resonances decaying into a top quark pair, or dark matter produced in association to a single-top or a top quark pair.

A data-driven, knowledge-based approach to biomarker discovery: application to circulating microRNA markers of colorectal cancer prognosis.

PubMed

Vafaee, Fatemeh; Diakos, Connie; Kirschner, Michaela B; Reid, Glen; Michael, Michael Z; Horvath, Lisa G; Alinejad-Rokny, Hamid; Cheng, Zhangkai Jason; Kuncic, Zdenka; Clarke, Stephen

2018-01-01

Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex-omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches. In this era, effective integration of data-driven and knowledge-based approaches for biomarker identification has been recognised as key to improving the identification of high-performance biomarkers, and necessary for translational applications. Here, we have evaluated the role of circulating microRNA as a means of predicting the prognosis of patients with colorectal cancer, which is the second leading cause of cancer-related death worldwide. We have developed a multi-objective optimisation method that effectively integrates a data-driven approach with the knowledge obtained from the microRNA-mediated regulatory network to identify robust plasma microRNA signatures which are reliable in terms of predictive power as well as functional relevance. The proposed multi-objective framework has the capacity to adjust for conflicting biomarker objectives and to incorporate heterogeneous information facilitating systems approaches to biomarker discovery. We have found a prognostic signature of colorectal cancer comprising 11 circulating microRNAs. The identified signature predicts the patients' survival outcome and targets pathways underlying colorectal cancer progression. The altered expression of the identified microRNAs was confirmed in an independent public data set of plasma samples of patients in early stage vs advanced colorectal cancer. Furthermore, the generality of the proposed method was demonstrated across three publicly available miRNA data sets associated with biomarker studies in other diseases.

Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

PubMed

Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

2015-06-01

Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita

2009-04-03

Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors,more » genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.« less

Impedance-Based Structural Health Monitoring for Composite Laminates at Cryogenic Environments

NASA Technical Reports Server (NTRS)

Tseng, Kevin

2003-01-01

One of the important ways of increasing the payload in a reusable launch vehicle (RLV) is to replace heavy metallic materials by lightweight composite laminates. Among various parts and systems of the RLV, this project focuses on tanks containing cryogenic fuel. Historically, aluminum alloys have been used as the materials to construct fuel tanks for launch vehicles. To replace aluminum alloys with composite laminates or honeycomb materials, engineers have to make sure that the composites are free of defects before, during, and after launch. In addition to robust design and manufacturing procedures, the performance of the composite structures needs to be monitored constantly.In recent years, the impedance-based health monitoring technique has shown its promise in many applications. This technique makes use of the special properties of smart piezoelectric materials to identify the change of material properties due to the nucleation and progression of damage. The piezoceramic patch serves as a sensor and an actuator simultaneously. The piezoelectric patch is bonded onto an existing structure or embedded into a new structure and electrically excited at high frequencies. The signature (impedance or admittance) is extracted as a function of the exciting frequency and is compared with the baseline signature of the healthy state. The damage is quantified using root mean square deviation (RMSD) in the impedance signatures with respect to the baseline signature. A major advantage of this technique is that the procedure is nondestructive in nature and does not perturb the properties and performance of the materials and structures. This project aims at applying the impedance-based nondestructive testing technique to the damage identification of composite laminates at cryogenic temperature.

TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer.

PubMed

Jeselsohn, Rinath; Barry, William T; Migliaccio, Ilenia; Biagioni, Chiara; Zhao, Jin; De Tribolet-Hardy, Jonas; Guarducci, Cristina; Bonechi, Martina; Laing, Naomi; Winer, Eric P; Brown, Myles; Leo, Angelo Di; Malorni, Luca

2016-12-01

Fulvestrant is an estrogen receptor (ER) antagonist and an approved treatment for metastatic estrogen receptor-positive (ER + ) breast cancer. With the exception of ER levels, there are no established predictive biomarkers of response to single-agent fulvestrant. We attempted to identify a gene signature of response to fulvestrant in advanced breast cancer. Primary tumor samples from 134 patients enrolled in the phase III CONFIRM study of patients with metastatic ER + breast cancer comparing treatment with either 250 mg or 500 mg fulvestrant were collected for genome-wide transcriptomic analysis. Gene expression profiling was performed using Affymetrix microarrays. An exploratory analysis was performed to identify biologic pathways and new signatures associated with response to fulvestrant. Pathway analysis demonstrated that increased EGF pathway and FOXA1 transcriptional signaling is associated with decreased response to fulvestrant. Using a multivariate Cox model, we identified a novel set of 37 genes with an expression that is independently associated with progression-free survival (PFS). TFAP2C, a known regulator of ER activity, was ranked second in this gene set, and high expression was associated with a decreased response to fulvestrant. The negative predictive value of TFAP2C expression at the protein level was confirmed by IHC. We identified biologic pathways and a novel gene signature in primary ER + breast cancers that predicts for response to treatment in the CONFIRM study. These results suggest potential new therapeutic targets and warrant further validation as predictive biomarkers of fulvestrant treatment in metastatic breast cancer. Clin Cancer Res; 22(23); 5755-64. ©2016 AACR. ©2016 American Association for Cancer Research.

Towards hydrochemical PUB - stable vs. heterogeneous NO3 and COD signatures across hydrographic structure and size

NASA Astrophysics Data System (ADS)

Ecrepont, Stephane; Cudennec, Christophe; Jaffrezic, Anne; de Lavenne, Alban

2017-04-01

Towards hydrochemical PUB - stable vs. heterogeneous NO3 and DOC signatures across hydrographic structure and size Ecrepont, S.1Cudennec, C.1 Jaffrézic, A.1 de Lavenne, A.2 1UMR SAS, Agrocampus Ouest, Rennes, France 2 HBAN, Irstea, Antony, France Intensive agriculture is a major disturbing factor for water quality in Brittany, France. Observations of chemical data from 350 catchments over a 15 year period show that the high variability of hydrochemical dynamics between catchments in relation to geographic characteristics and farming practices, decreases with an increase in the catchment size. A stable signature of nitrate and DOC dynamics does emerge for bigger catchments, and was evidenced statistically. We adapted a modified version of the standard deviation formula to calculate an index on mean inter-annual winter nitrate and dissolved organic carbon concentrations to characterize each catchment. The method was applied to the whole sample of catchments, some of them nested, to investigate variation of our new index across scales and regions. Results show an increasing and non-linear relationship between the criterion and the surface, with threshold effects. The stability of the thresholds across river basins in Brittany, and across seasons and years is explored. This emergence relates to the progressive connection of streams with heterogeneous characteristic chemical signatures into a mixing dominant effect. The better assessment of this relationship opens two major perspectives: i) to define a geomorphology-based PUB (Prediction in Ungauged Basins) approach for hydrochemistry; ii) to identify the most critical sub-catchments for mitigating actions in terms of farming and landscape practices towards water quality recovery.

Pilot study for supervised target detection applied to spatially registered multiparametric MRI in order to non-invasively score prostate cancer.

PubMed

Mayer, Rulon; Simone, Charles B; Skinner, William; Turkbey, Baris; Choykey, Peter

2018-03-01

Gleason Score (GS) is a validated predictor of prostate cancer (PCa) disease progression and outcomes. GS from invasive needle biopsies suffers from significant inter-observer variability and possible sampling error, leading to underestimating disease severity ("underscoring") and can result in possible complications. A robust non-invasive image-based approach is, therefore, needed. Use spatially registered multi-parametric MRI (MP-MRI), signatures, and supervised target detection algorithms (STDA) to non-invasively GS PCa at the voxel level. This study retrospectively analyzed 26 MP-MRI from The Cancer Imaging Archive. The MP-MRI (T2, Diffusion Weighted, Dynamic Contrast Enhanced) were spatially registered to each other, combined into stacks, and stitched together to form hypercubes. Multi-parametric (or multi-spectral) signatures derived from a training set of registered MP-MRI were transformed using statistics-based Whitening-Dewhitening (WD). Transformed signatures were inserted into STDA (having conical decision surfaces) applied to registered MP-MRI determined the tumor GS. The MRI-derived GS was quantitatively compared to the pathologist's assessment of the histology of sectioned whole mount prostates from patients who underwent radical prostatectomy. In addition, a meta-analysis of 17 studies of needle biopsy determined GS with confusion matrices and was compared to the MRI-determined GS. STDA and histology determined GS are highly correlated (R = 0.86, p < 0.02). STDA more accurately determined GS and reduced GS underscoring of PCa relative to needle biopsy as summarized by meta-analysis (p < 0.05). This pilot study found registered MP-MRI, STDA, and WD transforms of signatures shows promise in non-invasively GS PCa and reducing underscoring with high spatial resolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of the microRNA signature driving adaptive right ventricular hypertrophy in an ovine model of congenital heart disease.

PubMed

Kameny, Rebecca Johnson; He, Youping; Zhu, Terry; Gong, Wenhui; Raff, Gary W; Chapin, Cheryl J; Datar, Sanjeev A; Boehme, Jason; Hata, Akiko; Fineman, Jeffrey R

2018-06-15

The right ventricular (RV) response to pulmonary arterial hypertension (PAH) is heterogeneous. Most patients have maladaptive changes with RV dilation and failure while some-especially patients with PAH secondary to congenital heart disease (CHD)-have an adaptive response with hypertrophy and preserved systolic function. Mechanisms for RV adaptation to PAH are unknown despite RV function being a primary determinant of mortality. In our CHD ovine model with fetally-implanted aortopulmonary shunt (shunt lambs), we previously demonstrated an adaptive physiologic RV response to increased afterload with hypertrophy. In this study, we examined small noncoding microRNA (miRNA) expression in shunt RV and characterized downstream effects of a key miRNA. RV tissue was harvested from 4-week-old shunt and control lambs (n=5) and miRNA, mRNA, and proteins were quantitated. We found differential expression of 40 cardiovascular-specific miRNA in shunt RV. Interestingly, this miRNA signature is distinct from models of RV failure, suggesting that miRNAs might contribute to adaptive RV hypertrophy. Among RV miRNAs, miR-199b is decreased in RV with eventual downregulation of nuclear factor of activated T-cells (NFAT)/calcineurin signaling. Furthermore, anti-fibrotic miR-29a is increased in shunt RV with reduction of miR-29 targets Collagen A1 and 3A1 and decreased fibrosis. Thus, we conclude that the miRNA signature specific to shunt lambs is distinct from RV failure and drives gene expression required for adaptive RV hypertrophy. We propose that the adaptive RV miRNA signature may serve as a prognostic and therapeutic tool in patients with PAH to attenuate or prevent progression of RV failure and premature death.

Re-assessing Present Day Global Mass Transport and Glacial Isostatic Adjustment From a Data Driven Approach

NASA Astrophysics Data System (ADS)

Wu, X.; Jiang, Y.; Simonsen, S.; van den Broeke, M. R.; Ligtenberg, S.; Kuipers Munneke, P.; van der Wal, W.; Vermeersen, B. L. A.

2017-12-01

Determining present-day mass transport (PDMT) is complicated by the fact that most observations contain signals from both present day ice melting and Glacial Isostatic Adjustment (GIA). Despite decades of progress in geodynamic modeling and new observations, significant uncertainties remain in both. The key to separate present-day ice mass change and signals from GIA is to include data of different physical characteristics. We designed an approach to separate PDMT and GIA signatures by estimating them simultaneously using globally distributed interdisciplinary data with distinct physical information and a dynamically constructed a priori GIA model. We conducted a high-resolution global reappraisal of present-day ice mass balance with focus on Earth's polar regions and its contribution to global sea-level rise using a combination of ICESat, GRACE gravity, surface geodetic velocity data, and an ocean bottom pressure model. Adding ice altimetry supplies critically needed dual data types over the interiors of ice covered regions to enhance separation of PDMT and GIA signatures, and achieve half an order of magnitude expected higher accuracies for GIA and consequently ice mass balance estimates. The global data based approach can adequately address issues of PDMT and GIA induced geocenter motion and long-wavelength signatures important for large areas such as Antarctica and global mean sea level. In conjunction with the dense altimetry data, we solved for PDMT coefficients up to degree and order 180 by using a higher-resolution GRACE data set, and a high-resolution a priori PDMT model that includes detailed geographic boundaries. The high-resolution approach solves the problem of multiple resolutions in various data types, greatly reduces aliased errors from a low-degree truncation, and at the same time, enhances separation of signatures from adjacent regions such as Greenland and Canadian Arctic territories.

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

DOE PAGES

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn; ...

2017-11-27

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma

PubMed Central

Paulsson, Anna K.; Holmes, Jordan A.; Peiffer, Ann M.; Miller, Lance D.; Liu, Wennuan; Xu, Jianfeng; Hinson, William H.; Lesser, Glenn J.; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar

2014-01-01

We investigate the differences in molecular signature and clinical outcomes between multiple lesion glioblastoma (GBM) and single focus GBM in the modern treatment era. Between August 2000 and May 2010, 161 patients with GBM were treated with modern radiotherapy techniques. Of this group, 33 were considered to have multiple lesion GBM (25 multifocal and 8 multicentric). Patterns of failure, time to progression and overall survival were compared based on whether the tumor was considered a single focus or multiple lesion GBM. Genomic groupings and methylation status were also investigated as a possible predictor of multifocality in a cohort of 41 patients with available tissue for analysis. There was no statistically significant difference in overall survival (p < 0.3) between the multiple lesion tumors (8.2 months) and single focus GBM (11 months). Progression free survival was superior in the single focus tumors (7.1 months) as compared to multi-focal (5.6 months, p = 0.02). For patients with single focus, multifocal and multicentric GBM, 81, 76 and 88 % of treatment failures occurred in the 60 Gy volume (p < 0.5), while 54, 72, and 38 % of treatment failures occurred in the 46 Gy volume (p < 0.4). Out of field failures were rare in both single focus and multiple foci GBM (7 vs 3 %). Genomic groupings and methylation status were not found to predict for multifocality. Patterns of failure, survival and genomic signatures for multiple lesion GBM do not appreciably differ when compared to single focus tumors. PMID:24990827

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

PubMed Central

2014-01-01

Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray.

PubMed

Jinawath, Natini; Furukawa, Yoichi; Hasegawa, Suguru; Li, Meihua; Tsunoda, Tatsuhiko; Satoh, Seiji; Yamaguchi, Toshiharu; Imamura, Hiroshi; Inoue, Masatomo; Shiozaki, Hitoshi; Nakamura, Yusuke

2004-09-02

Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo

PubMed Central

Rashighi, Mehdi; Agarwal, Priti; Richmond, Jillian M; Harris, Tajie H; Dresser, Karen; Su, Mingwan; Zhou, Youwen; Deng, April; Hunter, Chris A; Luster, Andrew D; Harris, John E

2014-01-01

Vitiligo is an autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments for vitiligo, and most off-label treatments yield unsatisfactory results. Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8+ T cells in the skin and blood, which are directly responsible for melanocyte destruction. Here we report that gene expression in lesional skin from vitiligo patients reveals an IFN-γ-specific signature, including the chemokine CXCL10. CXCL10 is elevated in both vitiligo patient skin and serum and CXCR3, its receptor, is expressed on pathogenic T cells. To address the function of CXCL10 in vitiligo, we employed a mouse model of disease that also exhibits an IFN-γ-specific gene signature, expression of CXCL10 in the skin, and upregulation of CXCR3 on antigen-specific T cells. Mice that receive Cxcr3−/− T cells develop minimal depigmentation, as do mice lacking Cxcl10 or treated with CXCL10 neutralizing antibody. CXCL9 promotes autoreactive T cell global recruitment to the skin but not effector function while, in contrast, CXCL10 is required for effector function and localization within the skin. Surprisingly, CXCL10 neutralization in mice with established, widespread depigmentation induces reversal of disease, evidenced by repigmentation. These data identify a critical role for CXCL10 in both the progression and maintenance of vitiligo, and thereby support inhibiting CXCL10 as a targeted treatment strategy. PMID:24523323

Progression of trunk imbalance in adolescent idiopathic scoliosis with a thoracolumbar/lumbar curve: is it predictable at the initial visit?

PubMed

Hwang, Chang Ju; Lee, Choon Sung; Lee, Dong-Ho; Cho, Jae Hwan

2017-11-01

OBJECTIVE Progression of trunk imbalance is an important finding during follow-up of patients with adolescent idiopathic scoliosis (AIS). Nevertheless, no factors that predict progression of trunk imbalance have been identified. The purpose of this study was to identify parameters that predict progression of trunk imbalance in cases of AIS with a structural thoracolumbar/lumbar (TL/L) curve. METHODS This study included 105 patients with AIS and a structural TL/L curve who were followed up at an outpatient clinic. Patients with trunk imbalance (trunk shift ≥ 20 mm) at the initial visit were excluded. All patients were followed up for more than 2 years. Patients were divided into the following groups according to progression of trunk imbalance: 1) Group P, trunk shift ≥ 20 mm at the final visit and degree of progression ≥ 10 mm; and 2) Group NP, trunk shift < 20 mm at the final visit or degree of progression < 10 mm. Radiological parameters included Cobb angle, upper end vertebrae and lower end vertebrae (LEV), LEV tilt, disc wedge angle between LEV and LEV+1, trunk shift, apical vertebral translation, and apical vertebral rotation (AVR). Each parameter was compared between groups. Radiological parameters were assessed at every visit using whole-spine standing anteroposterior radiographs. RESULTS Among the 105 patients examined, 13 showed trunk imbalance with progression ≥ 10 mm at the final visit (Group P). Multivariate logistic regression analysis identified a lower Risser grade (p = 0.002) and a greater initial AVR (p = 0.020) as predictors of progressive trunk imbalance. A change in LEV tilt during follow-up was associated with trunk imbalance (p = 0.001). CONCLUSIONS Risser grade and AVR measured at the initial visit may predict progression of trunk imbalance. Surgeons should consider the risk of progressive trunk imbalance if patients show skeletal immaturity and a greater AVR at the initial visit.

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Distinctive Pattern of Serum Elements During the Progression of Alzheimer’s Disease

PubMed Central

Paglia, Giuseppe; Miedico, Oto; Cristofano, Adriana; Vitale, Michela; Angiolillo, Antonella; Chiaravalle, Antonio Eugenio; Corso, Gaetano; Di Costanzo, Alfonso

2016-01-01

Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer’s disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the study. Manganese, iron, copper, zinc, selenium, thallium, antimony, mercury, vanadium and molybdenum changed significantly among the 4 groups. Several essential elements, such as manganese, selenium, zinc and iron tended to increase in SMC and then progressively to decrease in MCI and AD. Toxic elements show a variable behavior, since some elements tended to increase, while others tended to decrease in AD. A multivariate model, built using a panel of six essential elements (manganese, iron, copper, zinc, selenium and calcium) and their ratios, discriminated AD patients from HS with over 90% accuracy. These findings suggest that essential and toxic elements contribute to generate a distinctive signature during the progression of AD, and their monitoring in elderly might help to detect preclinical stages of AD. PMID:26957294

Distinctive Pattern of Serum Elements During the Progression of Alzheimer's Disease.

PubMed

Paglia, Giuseppe; Miedico, Oto; Cristofano, Adriana; Vitale, Michela; Angiolillo, Antonella; Chiaravalle, Antonio Eugenio; Corso, Gaetano; Di Costanzo, Alfonso

2016-03-09

Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer's disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the study. Manganese, iron, copper, zinc, selenium, thallium, antimony, mercury, vanadium and molybdenum changed significantly among the 4 groups. Several essential elements, such as manganese, selenium, zinc and iron tended to increase in SMC and then progressively to decrease in MCI and AD. Toxic elements show a variable behavior, since some elements tended to increase, while others tended to decrease in AD. A multivariate model, built using a panel of six essential elements (manganese, iron, copper, zinc, selenium and calcium) and their ratios, discriminated AD patients from HS with over 90% accuracy. These findings suggest that essential and toxic elements contribute to generate a distinctive signature during the progression of AD, and their monitoring in elderly might help to detect preclinical stages of AD.

Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

PubMed Central

Lafyatis, Robert; Burkly, Linda C.

2017-01-01

Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. PMID:28662216

The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.

PubMed

McEvoy, Brian; Beleza, Sandra; Shriver, Mark D

2006-10-15

Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. On the basis of these results and other similar work, we provide a tentative three-population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history, with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian population, whereas most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly refine our understanding of the trait.

The Mg isotopic systematics of granitoids in continental arcs and implications for the role of chemical weathering in crust formation

PubMed Central

Shen, Bing; Jacobsen, Benjamin; Lee, Cin-Ty A.; Yin, Qing-Zhu; Morton, Douglas M.

2009-01-01

Continental crust is too Si-rich and Mg-poor to derive directly from mantle melting, which generates basaltic rather than felsic magmas. Converting basalt to more felsic compositions requires a second step involving Mg loss, which is thought to be dominated by internal igneous differentiation. However, igneous differentiation alone may not be able to generate granites, the most silicic endmember making up the upper continental crust. Here, we show that granites from the eastern Peninsular Ranges Batholith (PRB) in southern California are isotopically heavy in Mg compared with PRB granodiorites and canonical mantle. Specifically, Mg isotopes correlate positively with Si content and O, Sr, and Pb isotopes and negatively with Mg content. The elevated Sr and Pb isotopes require that a component in the source of the granitic magmas to be ancient preexisting crust making up the prebatholithic crustal basement, but the accompanying O and Mg isotope fractionations suggest that this prebatholithic crust preserved a signature of low-temperature alteration. The protolith of this basement rock may have been the residue of chemical weathering, which progressively leached Mg from the residue, leaving the remaining Mg highly fractionated in terms of its isotopic signature. Our observations indicate that ancient continental crust preserves the isotopic signature of compositional modification by chemical weathering. PMID:19920171

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

PubMed Central

Kocevar, Nina; Komel, Radovan

2014-01-01

Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

Predictive Engineering Tools for Injection-Molded Long-Carbon-Fiber Thermoplastic Composites - FY13 Fourth Quarterly Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Ba Nghiep; Simmons, Kevin L.

2013-12-02

This quarterly report summarizes the status of the project planning to obtain all the approvals required for a Cooperative Research and Development Agreement (CRADA) with Autodesk, Inc., Toyota Motor Engineering and Manufacturing North America (Toyota), and Magna Exterior and Interiors Corporation (Magna). The final CRADA documents processed by PNNL’s Legal Services were submitted to all the parties for signatures.

DESPIC: Detecting Early Signatures of Persuasion in Information Cascades

DTIC Science & Technology

2015-08-27

over NoSQL Databases, Proceedings of the 14th IEEE/ACM International Symposium on Cluster, Cloud and Grid Computing (CCGrid 2014). 26-MAY-14, . : , P...over NoSQL Databases. Proceedings of the 14th IEEE/ACM International Symposium on Cluster, Cloud and Grid Computing (CCGrid 2014). Chicago, IL, USA...distributed NoSQL databases including HBase and Riak, we finalized the requirements of the optimal computational architecture to support our framework

Observational and theoretical investigations in solar seismology

NASA Technical Reports Server (NTRS)

Noyes, Robert W.

1992-01-01

This is the final report on a project to develop a theoretical basis for interpreting solar oscillation data in terms of the interior dynamics and structure of the Sun. The topics covered include the following: (1) studies of the helioseismic signatures of differential rotation and convection in the solar interior; (2) wave generation by turbulent convection; and (3) the study of antipodal sunspot imaging of an active region tomography.

Creating a dashboard to track progress toward IOM recommendations for the future of nursing.

PubMed

Spetz, Joanne; Bates, Timothy; Chu, Lela; Lin, Jessica; Fishman, Nancy W; Melichar, Lori

2013-01-01

This article explains the process used to identify and develop a set of data used to track national progress toward the recommendations of the Institute of Medicine Committee for the Future of Nursing. The data are presented in a dashboard format to visually summarize information and quickly measure progress. The approach selected by the research team is outlined, the criteria for selecting candidate metrics are detailed, the process for seeking external guidance is described, and the final dashboard measures are presented. Finally, the methods for data collection for each metric are explicated, to guide states and local regions in the collection of their own data.

Water isotope partitioning and ecohydrologic separation in mixed conifer forest explored with a centrifugation water extraction method

NASA Astrophysics Data System (ADS)

Bowers, W.; Mercer, J.; Pleasants, M.; Williams, D. G.

2017-12-01

Isotopic partitioning of water within soil into tightly and loosely bound fractions has been proposed to explain differences between isotopic water sources used by plants and those that contribute to streams and ground water, the basis for the "two water worlds" hypothesis. We examined the isotope ratio values of water in trees, bulk soil, mobile water collected from soil lysimeters, stream water, and GW at three different hillslopes in a mixed conifer forest in southeastern Wyoming, USA. Hillslopes differed in aspect and topographic position with corresponding differences in surface energy balance, snowmelt timing, and duration of soil moisture during the dry summer. The isotopic results support the partitioning of water within the soil; trees apparently used a different pool of water for transpiration than that recovered from soil lysimeters and the source was not resolved with the isotopic signature of the water that was extracted from bulk soil via cryogenic vacuum distillation. Separating and measuring the isotope ratios values in these pools would test the assumption that the tightly bound water within the soil has the same isotopic signature as the water transpired by the trees. We employed a centrifugation approach to separate water within the soil held at different tensions by applying stepwise increases in rotational velocity and pressures to the bulk soil samples. Effluent and the remaining water (cryogenically extracted) at each step were compared. We first applied the centrifugation method in a simple lab experiment using sandy loam soil and separate introductions of two isotopically distinct waters. We then applied the method to soil collected from the montane hillslopes. For the lab experiment, we predicted that effluents would have distinct isotopic signatures, with the last effluent and extracted water more closely representing the isotopic signature of the first water applied. For our field samples, we predicted that the isotopic signature of the water discharged in the last centrifuge step and final extraction would more closely represent the isotopic signature of water extracted from trees. Understanding the isotopic partitioning of water within soil is important for interpreting plant water isotope values within the context of the "two water worlds" hypothesis.

Mapping the Natchez Trace Parkway

USGS Publications Warehouse

Rangoonwala, Amina; Bannister, Terri; Ramsey, Elijah W.

2011-01-01

Based on a National Park Service (NPS) landcover classification, a landcover map of the 715-km (444-mile) NPS Natchez Trace Parkway (hereafter referred to as the "Parkway") was created. The NPS landcover classification followed National Vegetation Classification (NVC) protocols. The landcover map, which extended the initial landcover classification to the entire Parkway, was based on color-infrared photography converted to 1-m raster-based digital orthophoto quarter quadrangles, according to U.S. Geological Survey mapping standards. Our goal was to include as many alliance classes as possible in the Parkway landcover map. To reach this goal while maintaining a consistent and quantifiable map product throughout the Parkway extent, a mapping strategy was implemented based on the migration of class-based spectral textural signatures and the congruent progressive refinement of those class signatures along the Parkway. Progressive refinement provided consistent mapping by evaluating the spectral textural distinctiveness of the alliance-association classes, and where necessary, introducing new map classes along the Parkway. By following this mapping strategy, the use of raster-based image processing and geographic information system analyses for the map production provided a quantitative and reproducible product. Although field-site classification data were severely limited, the combination of spectral migration of class membership along the Parkway and the progressive classification strategy produced an organization of alliances that was internally highly consistent. The organization resulted from the natural patterns or alignments of spectral variance and the determination of those spectral patterns that were compositionally similar in the dominant species as NVC alliances. Overall, the mapped landcovers represented the existent spectral textural patterns that defined and encompassed the complex variety of compositional alliances and associations of the Parkway. Based on that mapped representation, forests dominate the Parkway landscape. Grass is the second largest Parkway land cover, followed by scrub-shrub and shrubland classes and pine plantations. The map provides a good representation of the landcover patterns and their changes over the extent of the Parkway, south to north.

High-Speed Research: Sonic Boom, volume 1

NASA Technical Reports Server (NTRS)

Darden, Christine M. (Compiler)

1992-01-01

A High-Speed Sonic Boom Workshop was held at LaRC of Feb. 25-27, 1992. The purpose was to make presentations on current research activities and accomplishments and to assess progress in the area of sonic boom since the program was initiated in FY-90. Twenty-nine papers were presented during the 2-1/2 day workshop. Attendees included representatives from academia, industry, and government who are actively involved in sonic-boom research. Volume 1 contains papers related to atmospheric effects on the sonic-boom signature during propagation and on acceptability studies.

Horizontal Two Phase Flow Regime Identification: Comparison of Pressure Signature, Electrical Capacitance Tomography (ECT) and High Speed Visualization (Postprint)

DTIC Science & Technology

2012-11-01

W., and Mudawar , I., "Measurement and Correlation of Critical Heat Flux in Two-Phase Micro-Channel Heat Sinks," International Journal of Heat and...Mass Transfer, Vol. 47, No. 10-11, 2004, pp. 2045-2059. 3 Zhang, H., Mudawar , I., and Hasan, M. M., "Photographic Study of High-Flux Subcooled Flow...component Fow in Pipes," Chemical Engineering Progress, Vol. 45, 1949, pp. 39-48. 34 Qu, W., and Mudawar , I., "Measurement and Prediction of Pressure

Replacement, Reduction, Refinement - Animal welfare progress in European Pharmacopoeia monographs: activities of the European Pharmacopoeia Commission from 2007 to 2017.

PubMed

Lang, C; Kolaj-Robin, O; Cirefice, G; Taconet, L; Pel, E; Jouette, S; Buda, M; Milne, C; Charton, E

2018-01-01

Since the opening for signature of the European Convention for the Protection of Animals Used for Experimental and Other Scientific Purposes in 1986, the European Pharmacopoeia Commission and its experts have carried out a programme of work committed to Replacing, Reducing and Refining (3Rs) the use of animals for test purposes. While updates on achievements in the field of the 3Rs are regularly provided, this article summarises the activities of the Ph. Eur. Commission in this field within the last decade.

Astrometric cosmology .

NASA Astrophysics Data System (ADS)

Lattanzi, M. G.

The accurate measurement of the motions of stars in our Galaxy can provide access to the cosmological signatures in the disk and halo, while astrometric experiments from within our Solar System can uniquely probe possible deviations from General Relativity. This article will introduce to the fact that astrometry has the potential, thanks also to impressive technological advancements, to become a key player in the field of local cosmology. For example, accurate absolute kinematics at the scale of the Milky Way can, for the first time in situ, account for the predictions made by the cold dark matter model for the Galactic halo, and eventually map out the distribution of dark matter, or other formation mechanisms, required to explain the signatures recently identified in the old component of the thick disk. Final notes dwell on to what extent Gaia can fulfill the expectations of astrometric cosmology and on what must instead be left to future, specifically designed, astrometric experiments.

A restricted signature normal form for Hermitian matrices, quasi-spectral decompositions, and applications

NASA Technical Reports Server (NTRS)

Freund, Roland W.; Huckle, Thomas

1989-01-01

In recent years, a number of results on the relationships between the inertias of Hermitian matrices and the inertias of their principal submatrices appeared in the literature. We study restricted congruence transformation of Hermitian matrices M which, at the same time, induce a congruence transformation of a given principal submatrix A of M. Such transformations lead to concept of the restricted signature normal form of M. In particular, by means of this normal form, we obtain short proofs of most of the known inertia theorems and also derive some new results of this type. For some applications, a special class of almost unitary restricted congruence transformations turns out to be useful. We show that, with such transformations, M can be reduced to a quasi-diagonal form which, in particular, displays the eigenvalues of A. Finally, applications of this quasi-spectral decomposition to generalize inverses and Hermitian matrix pencils are discussed.

Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines

PubMed Central

Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

2014-01-01

The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines. PMID:25335753

Echoes of the electroweak phase transition: discovering a second Higgs doublet through A0→ZH0.

PubMed

Dorsch, G C; Huber, S J; Mimasu, K; No, J M

2014-11-21

The existence of a second Higgs doublet in nature could lead to a cosmological first-order electroweak phase transition and explain the origin of the matter-antimatter asymmetry in the Universe. We obtain the spectrum and properties of the new scalars H0, A0, and H(±) that signal such a phase transition and show that the observation of the decay A0→ZH0 at LHC would be a "smoking gun" signature of these scenarios. We analyze the LHC search prospects for this decay in the ℓℓbb and ℓℓW(+)W(-) final states, arguing that current data may be sensitive to this signature in the former channel as well as there being great potential for a discovery in either channel at the very early stages of the 14 TeV run.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Cheng-Long; Xu, Su-Yang; Belopolski, Ilya

Weyl semimetals provide the realization of Weyl fermions in solid-state physics. Among all the physical phenomena that are enabled by Weyl semimetals, the chiral anomaly is the most unusual one. Here, we report signatures of the chiral anomaly in the magneto-transport measurements on the first Weyl semimetal TaAs. We show negative magnetoresistance under parallel electric and magnetic fields, that is, unlike most metals whose resistivity increases under an external magnetic field, we observe that our high mobility TaAs samples become more conductive as a magnetic field is applied along the direction of the current for certain ranges of the fieldmore » strength. We present systematically detailed data and careful analyses, which allow us to exclude other possible origins of the observed negative magnetoresistance. Finally, our transport data, corroborated by photoemission measurements, first-principles calculations and theoretical analyses, collectively demonstrate signatures of the Weyl fermion chiral anomaly in the magneto-transport of TaAs.« less

Search for gluinos and scalar quarks in pp collisions at square root[s] = 1.8 TeV using the missing energy plus multijets signature.

PubMed

Affolder, T; Akimoto, H; Akopian, A; Albrow, M G; Amaral, P; Amidei, D; Anikeev, K; Antos, J; Apollinari, G; Arisawa, T; Artikov, A; Asakawa, T; Ashmanskas, W; Azfar, F; Azzi-Bacchetta, P; Bacchetta, N; Bachacou, H; Bailey, S; de Barbaro, P; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Bauer, G; Bedeschi, F; Belforte, S; Bell, W H; Bellettini, G; Bellinger, J; Benjamin, D; Bensinger, J; Beretvas, A; Berge, J P; Berryhill, J; Bhatti, A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Blusk, S R; Bocci, A; Bodek, A; Bokhari, W; Bolla, G; Bonushkin, Y; Bortoletto, D; Boudreau, J; Brandl, A; van den Brink, S; Bromberg, C; Brozovic, M; Brubaker, E; Bruner, N; Buckley-Geer, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Byon-Wagner, A; Byrum, K L; Cabrera, S; Calafiura, P; Campbell, M; Carithers, W; Carlson, J; Carlsmith, D; Caskey, W; Castro, A; Cauz, D; Cerri, A; Chan, A W; Chang, P S; Chang, P T; Chapman, J; Chen, C; Chen, Y C; Cheng, M-T; Chertok, M; Chiarelli, G; Chirikov-Zorin, I; Chlachidze, G; Chlebana, F; Christofek, L; Chu, M L; Chung, Y S; Ciobanu, C I; Clark, A G; Connolly, A; Conway, J; Cordelli, M; Cranshaw, J; Cropp, R; Culbertson, R; Dagenhart, D; D'Auria, S; DeJongh, F; Dell'Agnello, S; Dell'Orso, M; Demortier, L; Deninno, M; Derwent, P F; Devlin, T; Dittmann, J R; Dominguez, A; Donati, S; Done, J; D'Onofrio, M; Dorigo, T; Eddy, N; Einsweiler, K; Elias, J E; Engels, E; Erbacher, R; Errede, D; Errede, S; Fan, Q; Feild, R G; Fernandez, J P; Ferretti, C; Field, R D; Fiori, I; Flaugher, B; Foster, G W; Franklin, M; Freeman, J; Friedman, J; Frisch, H J; Fukui, Y; Furic, I; Galeotti, S; Gallas, A; Gallinaro, M; Gao, T; Garcia-Sciveres, M; Garfinkel, A F; Gatti, P; Gay, C; Gerdes, D W; Giannetti, P; Giromini, P; Glagolev, V; Glenzinski, D; Gold, M; Goldstein, J; Gorelov, I; Goshaw, A T; Gotra, Y; Goulianos, K; Green, C; Grim, G; Gris, P; Groer, L; Grosso-Pilcher, C; Guenther, M; Guillian, G; Guimaraes da Costa, J; Haas, R M; Haber, C; Hahn, S R; Hall, C; Handa, T; Handler, R; Hao, W; Happacher, F; Hara, K; Hardman, A D; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Heinrich, J; Heiss, A; Herndon, M; Hill, C; Hoffman, K D; Holck, C; Hollebeek, R; Holloway, L; Hughes, R; Huston, J; Huth, J; Ikeda, H; Incandela, J; Introzzi, G; Iwai, J; Iwata, Y; James, E; Jones, M; Joshi, U; Kambara, H; Kamon, T; Kaneko, T; Karr, K; Kasha, H; Kato, Y; Keaffaber, T A; Kelley, K; Kelly, M; Kennedy, R D; Kephart, R; Khazins, D; Kikuchi, T; Kilminster, B; Kim, B J; Kim, D H; Kim, H S; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kirby, M; Kirk, M; Kirsch, L; Klimenko, S; Koehn, P; Kondo, K; Konigsberg, J; Korn, A; Korytov, A; Kovacs, E; Kroll, J; Kruse, M; Kuhlmann, S E; Kurino, K; Kuwabara, T; Laasanen, A T; Lai, N; Lami, S; Lammel, S; Lancaster, J; Lancaster, M; Lander, R; Lath, A; Latino, G; LeCompte, T; Lee, A M; Lee, K; Leone, S; Lewis, J D; Lindgren, M; Liss, T M; Liu, J B; Liu, Y C; Litvintsev, D O; Lobban, O; Lockyer, N; Loken, J; Loreti, M; Lucchesi, D; Lukens, P; Lusin, S; Lyons, L; Lys, J; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Mangano, M; Mariotti, M; Martignon, G; Martin, A; Matthews, J A J; Mayer, J; Mazzanti, P; McFarland, K S; McIntyre, P; McKigney, E; Menguzzato, M; Menzione, A; Mesropian, C; Meyer, A; Miao, T; Miller, R; Miller, J S; Minato, H; Miscetti, S; Mishina, M; Mitselmakher, G; Moggi, N; Moore, E; Moore, R; Morita, Y; Moulik, T; Mulhearn, M; Mukherjee, A; Muller, T; Munar, A; Murat, P; Murgia, S; Nachtman, J; Nagaslaev, V; Nahn, S; Nakada, H; Nakano, I; Nelson, C; Nelson, T; Neu, C; Neuberger, D; Newman-Holmes, C; Ngan, C-Y P; Niu, H; Nodulman, L; Nomerotski, A; Oh, S H; Oh, Y D; Ohmoto, T; Ohsugi, T; Oishi, R; Okusawa, T; Olsen, J; Orejudos, W; Pagliarone, C; Palmonari, F; Paoletti, R; Papadimitriou, V; Partos, D; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pescara, L; Phillips, T J; Piacentino, G; Pitts, K T; Pompos, A; Pondrom, L; Pope, G; Popovic, M; Prokoshin, F; Proudfoot, J; Ptohos, F; Pukhov, O; Punzi, G; Rakitine, A; Ratnikov, F; Reher, D; Reichold, A; Ribon, A; Riegler, W; Rimondi, F; Ristori, L; Riveline, M; Robertson, W J; Robinson, A; Rodrigo, T; Rolli, S; Rosenson, L; Roser, R; Rossin, R; Roy, A; Ruiz, A; Safonov, A; St Denis, R; Sakumoto, W K; Saltzberg, D; Sanchez, C; Sansoni, A; Santi, L; Sato, H; Savard, P; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Scodellaro, L; Scott, A; Scribano, A; Segler, S; Seidel, S; Seiya, Y; Semenov, A; Semeria, F; Shah, T; Shapiro, M D; Shepard, P F; Shibayama, T; Shimojima, M; Shochet, M; Sidoti, A; Siegrist, J; Sill, A; Sinervo, P; Singh, P; Slaughter, A J; Sliwa, K; Smith, C; Snider, F D; Solodsky, A; Spalding, J; Speer, T; Sphicas, P; Spinella, F; Spiropulu, M; Spiegel, L; Steele, J; Stefanini, A; Strologas, J; Strumia, F; Stuart, D; Sumorok, K; Suzuki, T; Takano, T; Takashima, R; Takikawa, K; Tamburello, P; Tanaka, M; Tannenbaum, B; Tecchio, M; Tesarek, R; Teng, P K; Terashi, K; Tether, S; Thompson, A S; Thurman-Keup, R; Tipton, P; Tkaczyk, S; Toback, D; Tollefson, K; Tollestrup, A; Tonelli, D; Toyoda, H; Trischuk, W; de Troconiz, J F; Tseng, J; Turini, N; Ukegawa, F; Vaiciulis, T; Valls, J; Vejcik, S; Velev, G; Veramendi, G; Vidal, R; Vila, I; Vilar, R; Volobouev, I; von der Mey, M; Vucinic, D; Wagner, R G; Wagner, R L; Wallace, N B; Wan, Z; Wang, C; Wang, M J; Ward, B; Waschke, S; Watanabe, T; Waters, D; Watts, T; Webb, R; Wenzel, H; Wester, W C; Wicklund, A B; Wicklund, E; Wilkes, T; Williams, H H; Wilson, P; Winer, B L; Winn, D; Wolbers, S; Wolinski, D; Wolinski, J; Wolinski, S; Worm, S; Wu, X; Wyss, J; Yao, W; Yagil, A; Yeh, G P; Yoh, J; Yosef, C; Yoshida, T; Yu, I; Yu, S; Yu, Z; Zanetti, A; Zetti, F; Zucchelli, S

2002-01-28

We have performed a search for gluinos (g) and scalar quarks (q) in a data sample of 84 pb(-1) of pp collisions at square root[s] = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and three or more jets, a characteristic signature in R-parity-conserving supersymmetric models. The analysis has been performed "blind," in that the inspection of the signal region is made only after the predictions from standard model backgrounds have been calculated. Comparing the data with predictions of constrained supersymmetric models, we exclude gluino masses below 195 GeV/c2 (95% C.L.), independent of the squark mass. For the case m(q) approximately m(g), gluino masses below 300 GeV/c2 are excluded.

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at √s=13 TeV

DOE PAGES

Aaboud, M.

2016-07-15

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb -1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s=13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Finally, exclusion limits are set for modelsmore » of microscopic black holes with two to six extra dimensions.« less

Stable isotopes, beaks and predators: a new tool to study the trophic ecology of cephalopods, including giant and colossal squids.

PubMed

Cherel, Yves; Hobson, Keith A

2005-08-07

Cephalopods play a key role in the marine environment but knowledge of their feeding habits is limited by lack of data. Here, we have developed a new tool to investigate their feeding ecology by combining the use of their predators as biological samplers together with measurements of the stable isotopic signature of their beaks. Cephalopod beaks are chitinous hard structures that resist digestion and the stable isotope ratios of carbon (delta13C) and nitrogen (delta15N) are indicators of the foraging areas and trophic levels of consumers, respectively. First, a comparison of delta13C and delta15N values of different tissues from the same individuals showed that beaks were slightly enriched in 13C but highly impoverished in 15N compared with lipid-free muscle tissues. Second, beaks from the same species showed a progressive increase in their delta15N values with increasing size, which is in agreement with a dietary shift from lower to higher trophic levels during cephalopod growth. In the same way, there was an increase in the delta15N signature of various parts of the same lower beaks in the order rostrum, lateral walls and wings, which reflects the progressive growth and chitinization of the beaks in parallel with dietary changes. Third, we investigated the trophic structure of a cephalopod community for the first time. Values of delta15N indicate that cephalopods living in slope waters of the subantarctic Kerguelen Islands (n=18 species) encompass almost three distinct trophic levels, with a continuum of two levels between crustacean- and fish-eaters and a distinct higher trophic level occupied by the colossal squid Mesonychoteuthis hamiltoni. delta13C values demonstrated that cephalopods grow in three different marine ecosystems, with 16 species living and developing in Kerguelen waters and two species migrating from either Antarctica (Slosarczykovia circumantarctica) or the subtropics (the giant squid Architeuthis dux). The stable isotopic signature of beaks accumulated in predators' stomachs therefore revealed new trophic relationships and migration patterns and is a powerful tool to investigate the role of the poorly known cephalopods in the marine environment.

A sensitive NanoString-based assay to score STK11 (LKB1) pathway disruption in lung adenocarcinoma

PubMed Central

Chen, Lu; Engel, Brienne E.; Welsh, Eric A.; Yoder, Sean J.; Brantley, Stephen G.; Chen, Dung-Tsa; Beg, Amer A.; Cao, Chunxia; Kaye, Frederic J.; Haura, Eric B.; Schabath, Matthew B.; Cress, W. Douglas

2016-01-01

Introduction Serine/threonine kinase 11 (STK11), better known as LKB1, is a tumor-suppressor commonly mutated in lung adenocarcinoma (LUAD). Previous work has shown that mutational inactivation of the STK11 pathway may serve as a predictive biomarker for cancer treatments including phenformin and COX-2 inhibition. Although immunohistochemistry and diagnostic sequencing are employed to measure STK11 pathway disruption, there are serious limitations to these methods emphasizing the importance to validate a clinically useful assay. Methods An initial STK11 mutation mRNA signature was generated using cell line data and refined using three large, independent patient databases. The signature was validated as a classifier using The Cancer Genome Anatomy Project (TCGA) LUAD cohort as well as a 442-patient LUAD cohort developed at Moffitt. Finally, the signature was adapted into a NanoString -based format and validated using RNA samples isolated from FFPE tissue blocks corresponding to a cohort of 150 LUAD patients. For comparison, STK11 immunochemistry was also performed. Results The STK11 signature was found to correlate with null mutations identified by exon sequencing in multiple cohorts using both microarray and NanoString formats. While there was a statistically significant correlation between reduced STK11 protein expression by IHC and mutation status, the NanoString-based assay showed superior overall performance with a −0.1588 improvement in area under the curve in receiver-operator characteristic curve analysis (p<0.012). Conclusion The described NanoString-based STK11 assay is a sensitive biomarker to study emerging therapeutic modalities in clinical trials. PMID:26917230

Progress in Understanding the Pre-Earthquake Associated Events by Analyzing IR Satellite Data

NASA Technical Reports Server (NTRS)

Ouzounov, Dimitar; Taylor, Patrick; Bryant, Nevin

2004-01-01

We present latest result in understanding the potential relationship between tectonic stress, electro-chemical and thermodynamic processes in the Earths crust and atmosphere with an increase in IR flux as a potential signature of electromagnetic (EM) phenomena that are related to earthquake activity, either pre-, co- or post seismic. Thermal infra-red (TIR) surveys performed by the polar orbiting (NOAA/AVHRR MODIS) and geosynchronous weather satellites (GOES, METEOSAT) gave an indication of the appearance (from days to weeks before the event) of "anomalous" space-time TIR transients that are associated with the location (epicenter and local tectonic structures) and time of a number of major earthquakes with M>5 and focal depths less than 50km. We analyzed broad category of associated pre-earthquake events, which provided evidence for changes in surface temperature, surface latent heat flux, chlorophyll concentrations, soil moisture, brightness temperature, emissivity of surface, water vapour in the atmosphere prior to the earthquakes occurred in Algeria, India, Iran, Italy, Mexico and Japan. The cause of such anomalies has been mainly related to the change of near-surface thermal properties due to complex lithosphere-hydrosphere-atmospheric interactions. As final results we present examples from the most recent (2000-2004) worldwide strong earthquakes and the techniques used to capture the tracks of EM emission mid-IR anomalies and a methodology for practical future use of such phenomena in the early warning systems.

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

PubMed

Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Stable isotope signatures for characterising the biological stability of landfilled municipal solid waste.

PubMed

Wimmer, Bernhard; Hrad, Marlies; Huber-Humer, Marion; Watzinger, Andrea; Wyhlidal, Stefan; Reichenauer, Thomas G

2013-10-01

Stable isotopic signatures of landfill leachates are influenced by processes within municipal solid waste (MSW) landfills mainly depending on the aerobic/anaerobic phase of the landfill. We investigated the isotopic signatures of δ(13)C, δ(2)H and δ(18)O of different leachates from lab-scale experiments, lysimeter experiments and a landfill under in situ aeration. In the laboratory, columns filled with MSW of different age and reactivity were percolated under aerobic and anaerobic conditions. In landfill simulation reactors, waste of a 25year old landfill was kept under aerobic and anaerobic conditions. The lysimeter facility was filled with mechanically shredded fresh waste. After starting of the methane production the waste in the lysimeter containments was aerated in situ. Leachate and gas composition were monitored continuously. In addition the seepage water of an old landfill was collected and analysed periodically before and during an in situ aeration. We found significant differences in the δ(13)C-value of the dissolved inorganic carbon (δ(13)C-DIC) of the leachate between aerobic and anaerobic waste material. During aerobic degradation, the signature of δ(13)C-DIC was mainly dependent on the isotopic composition of the organic matter in the waste, resulting in a δ(13)C-DIC of -20‰ to -25‰. The production of methane under anaerobic conditions caused an increase in δ(13)C-DIC up to values of +10‰ and higher depending on the actual reactivity of the MSW. During aeration of a landfill the aerobic degradation of the remaining organic matter caused a decrease to a δ(13)C-DIC of about -20‰. Therefore carbon isotope analysis in leachates and groundwater can be used for tracing the oxidation-reduction status of MSW landfills. Our results indicate that monitoring of stable isotopic signatures of landfill leachates over a longer time period (e.g. during in situ aeration) is a powerful and cost-effective tool for characterising the biodegradability and stability of the organic matter in landfilled municipal solid waste and can be used for monitoring the progress of in situ aeration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurement of the WW + WZ production cross section using the lepton + jets final state at CDF II.

PubMed

Aaltonen, T; Adelman, J; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; d'Errico, M; Di Canto, A; di Giovanni, G P; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, T; Dube, S; Ebina, K; Elagin, A; Erbacher, R; Errede, D; Errede, S; Ershaidat, N; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Hughes, R E; Hurwitz, M; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leone, S; Lewis, J D; Lin, C-J; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Lovas, L; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Mastrandrea, P; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Mesropian, C; Miao, T; Mietlicki, D; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramanov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Potamianos, K; Poukhov, O; Prokoshin, F; Pronko, A; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Santi, L; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Simonenko, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Suh, J S; Sukhanov, A; Suslov, I; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wolfe, H; Wright, T; Wu, X; Würthwein, F; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhang, X; Zheng, Y; Zucchelli, S

2010-03-12

We report two complementary measurements of the WW + WZ cross section in the final state consisting of an electron or muon, missing transverse energy, and jets, performed using pp collision data at square root of s = 1.96 TeV collected by the CDF II detector. The first method uses the dijet invariant mass distribution while the second more sensitive method uses matrix-element calculations. The result from the second method has a signal significance of 5.4sigma and is the first observation of WW + WZ production using this signature. Combining the results gives sigma(WW + WZ) = 16.0 +/- 3.3 pb, in agreement with the standard model prediction.

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Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

PubMed

Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

2015-05-01

Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.

Simulation of the vibrational chemistry and the infrared signature induced by a Sprite streamer in the mesosphere

NASA Astrophysics Data System (ADS)

Romand, F.; Payan, S.; Croize, L.

2017-12-01

Since their first observation in 1989, effect of TLEs on the atmospheric composition has become an open and important question. The lack of suitable experimental data is a shortcoming that hampers our understanding of the physics and chemistry induced by these effects. HALESIS (High-Altitude Luminous Events Studied by Infrared Spectro-imagery) is a future experiment dedicated to the measurement of the atmospheric perturbation induced by a TLE in the minutes following its occurrence, from a stratospheric balloon flying at an altitude of 25 km to 40 km. This work aims to quantify the local chemical impact of sprites in the stratosphere and mesosphere. In this paper, we will present the development of a tool which simulates (i) the impact of a sprite on the vibrational chemistry, (ii) the resulting infrared signature and (iii) the propagation of this signature through the atmosphere to an observer. First the Non Local Thermodynamic Equilibrium populations of a background atmosphere were computed using SAMM2 code. The initial thermodynamic and chemical description of atmosphere comes from the Whole Atmosphere community Climate Model (WACCM). Then a perturbation was applied to simulate a sprite. Chemistry due to TLEs was computed using Gordillo-Vazquez kinetic model. Rate coefficients that depend on the electron energy distribution function were calculated from collision cross-section data by solving the electron Boltzmann equation (BE). Time evolutions of the species densities and of vibrational populations in the non-thermal plasma consecutive to sprite discharge were simulated using the computer code ZDPlasKin (S. Pancheshn et al.). Finally, the resulting infrared signatures were propagated from the disturbed area through the atmosphere to an instrument placed in a limb line of sight using a line by line radiative transfer model. We will conclude that sprite could produce a significant infrared signature that last a few tens of seconds after the visible flash.

Combining Gene Signatures Improves Prediction of Breast Cancer Survival

PubMed Central

Zhao, Xi; Naume, Bjørn; Langerød, Anita; Frigessi, Arnoldo; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingjærde, Ole Christian

2011-01-01

Background Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123) and test set (n = 81), respectively. Gene sets from eleven previously published gene signatures are included in the study. Principal Findings To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014). Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001). The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. Conclusion Combining the predictive strength of multiple gene signatures improves prediction of breast cancer survival. The presented methodology is broadly applicable to breast cancer risk assessment using any new identified gene set. PMID:21423775

Radiation Belt Dynamics

DTIC Science & Technology

2015-12-27

is unlimited. 15 DISTRIBUTION LIST DTIC/OCP 8725 John J. Kingman Rd, Suite 0944 Ft Belvoir, VA 22060-6218 1 cy AFRL /RVIL Kirtland AFB, NM 87117... AFRL -RV-PS- AFRL -RV-PS- TR-2016-0007 TR-2016-0007 RADIATION BELT DYNAMICS Jay M. Albert, et al. 27 December 2015 Final Report APPROVED FOR... KIRTLAND AIR FORCE BASE, NM 87117-5776 DTIC COPY NOTICE AND SIGNATURE PAGE Using Government drawings, specifications, or other data included in this

Dissociable neural response signatures for slow amplitude and frequency modulation in human auditory cortex.

PubMed

Henry, Molly J; Obleser, Jonas

2013-01-01

Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals.

Dissociable Neural Response Signatures for Slow Amplitude and Frequency Modulation in Human Auditory Cortex

PubMed Central

Henry, Molly J.; Obleser, Jonas

2013-01-01

Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals. PMID:24205309

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Targeting renal cell carcinoma with a HIF-2 antagonist.

PubMed

Chen, Wenfang; Hill, Haley; Christie, Alana; Kim, Min Soo; Holloman, Eboni; Pavia-Jimenez, Andrea; Homayoun, Farrah; Ma, Yuanqing; Patel, Nirav; Yell, Paul; Hao, Guiyang; Yousuf, Qurratulain; Joyce, Allison; Pedrosa, Ivan; Geiger, Heather; Zhang, He; Chang, Jenny; Gardner, Kevin H; Bruick, Richard K; Reeves, Catherine; Hwang, Tae Hyun; Courtney, Kevin; Frenkel, Eugene; Sun, Xiankai; Zojwalla, Naseem; Wong, Tai; Rizzi, James P; Wallace, Eli M; Josey, John A; Xie, Yang; Xie, Xian-Jin; Kapur, Payal; McKay, Renée M; Brugarolas, James

2016-11-03

Clear cell renal cell carcinoma (ccRCC) is characterized by inactivation of the von Hippel-Lindau tumour suppressor gene (VHL). Because no other gene is mutated as frequently in ccRCC and VHL mutations are truncal, VHL inactivation is regarded as the governing event. VHL loss activates the HIF-2 transcription factor, and constitutive HIF-2 activity restores tumorigenesis in VHL-reconstituted ccRCC cells. HIF-2 has been implicated in angiogenesis and multiple other processes, but angiogenesis is the main target of drugs such as the tyrosine kinase inhibitor sunitinib. HIF-2 has been regarded as undruggable. Here we use a tumourgraft/patient-derived xenograft platform to evaluate PT2399, a selective HIF-2 antagonist that was identified using a structure-based design approach. PT2399 dissociated HIF-2 (an obligatory heterodimer of HIF-2α-HIF-1β) in human ccRCC cells and suppressed tumorigenesis in 56% (10 out of 18) of such lines. PT2399 had greater activity than sunitinib, was active in sunitinib-progressing tumours, and was better tolerated. Unexpectedly, some VHL-mutant ccRCCs were resistant to PT2399. Resistance occurred despite HIF-2 dissociation in tumours and evidence of Hif-2 inhibition in the mouse, as determined by suppression of circulating erythropoietin, a HIF-2 target and possible pharmacodynamic marker. We identified a HIF-2-dependent gene signature in sensitive tumours. Gene expression was largely unaffected by PT2399 in resistant tumours, illustrating the specificity of the drug. Sensitive tumours exhibited a distinguishing gene expression signature and generally higher levels of HIF-2α. Prolonged PT2399 treatment led to resistance. We identified binding site and second site suppressor mutations in HIF-2α and HIF-1β, respectively. Both mutations preserved HIF-2 dimers despite treatment with PT2399. Finally, an extensively pretreated patient whose tumour had given rise to a sensitive tumourgraft showed disease control for more than 11 months when treated with a close analogue of PT2399, PT2385. We validate HIF-2 as a target in ccRCC, show that some ccRCCs are HIF-2 independent, and set the stage for biomarker-driven clinical trials.

Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites.

PubMed

Polite, Blase N; Dignam, James J; Olopade, Olufunmilayo I

2005-07-01

Understanding the differences in the incidence and mortality rate between African Americans and whites with CRC remains a perplexing problem. There is clearly not any one factor that explains the observed differences. Clinicians are just beginning to understand the importance of tumor biology, genetics, and lifestyle risk factors in explaining differences in how CRCs present and how they behave. This holds true regardless of a patient's race, sex, or age. Whether these factors will add disproportionately to the understanding of racial differences in presentation and outcome remains to be seen. Certainly, issues surrounding screening for CRC remain important in understanding the advanced stage of presentation for African Americans. In particular, a better understanding is needed of who is being screened and who is not and why. For example, are higher-risk African Americans being screened and if not what are the reasons for this? Importantly, even if one were able to eliminate the differences in stage at presentation between African Americans and whites, a survival disadvantage, albeit a much smaller one, would likely persist. Clearly, there is a need to understand better why African Americans are not receiving recommended therapy at the same rate as whites. This becomes even more important as the life-prolonging options for treating both localized and metastatic colon cancer continue to multiply. Finally, the apparent greater disparity in outcome for African Americans who have stage II disease should be explored in more detail, because this could have an immediate impact on treatment recommendations. For example, a 23-gene signature was recently found to be predictive of recurrence among patients with Dukes B colon cancer [66]. If this model is validated in further studies, one could look at whether African-American patients are more likely to have this predictive signature. The problem has been clearly defined: a higher incidence of and a higher mortality from CRC for African Americans than whites. The task now becomes to continue to understand the reasons for the disparities and ultimately to come up with workable solutions so that the amazing progress in CRC treatment benefits all groups in this country.

The thermal decomposition of fine-grained micrometeorites, observations from mid-IR spectroscopy

NASA Astrophysics Data System (ADS)

Suttle, Martin David; Genge, Matthew J.; Folco, Luigi; Russell, Sara S.

2017-06-01

We analysed 44 fine-grained and scoriaceous micrometeorites. A bulk mid-IR spectrum (8-13 μm) for each grain was collected and the entire micrometeorite population classified into 5 spectral groups, based on the positions of their absorption bands. Corresponding carbonaceous Raman spectra, textural observations from SEM-BSE and bulk geochemical data via EMPA were collected to aid in the interpretation of mid-IR spectra. The 5 spectral groups identified correspond to progressive thermal decomposition. Unheated hydrated chondritic matrix, composed predominantly of phyllosilicates, exhibit smooth, asymmetric spectra with a peak at ∼10 μm. Thermal decomposition of sheet silicates evolves through dehydration, dehydroxylation, annealing and finally by the onset of partial melting. Both CI-like and CM-like micrometeorites are shown to pass through the same decomposition stages and produce similar mid-IR spectra. Using known temperature thresholds for each decomposition stage it is possible to assign a peak temperature range to a given micrometeorite. Since the temperature thresholds for decomposition reactions are defined by the phyllosilicate species and the cation composition and that these variables are markedly different between CM and CI classes, atmospheric entry should bias the dust flux to favour the survival of CI-like grains, whilst preferentially melting most CM-like dust. However, this hypothesis is inconsistent with empirical observations and instead requires that the source ratio of CI:CM dust is heavily skewed in favour of CM material. In addition, a small population of anomalous grains are identified whose carbonaceous and petrographic characteristics suggest in-space heating and dehydroxylation have occurred. These grains may therefore represent regolith micrometeorites derived from the surface of C-type asteroids. Since the spectroscopic signatures of dehydroxylates are distinctive, i.e. characterised by a reflectance peak at 9.0-9.5 μm, and since the surfaces of C-type asteroids are expected to be heated via impact gardening, we suggest that future spectroscopic investigations should attempt to identify dehydroxylate signatures in the reflectance spectra of young carbonaceous asteroid families.

Active sensors for health monitoring of aging aerospace structures

NASA Astrophysics Data System (ADS)

Giurgiutiu, Victor; Redmond, James M.; Roach, Dennis P.; Rackow, Kirk

2000-06-01

A project to develop non-intrusive active sensors that can be applied on existing aging aerospace structures for monitoring the onset and progress of structural damage (fatigue cracks and corrosion) is presented. The state of the art in active sensors structural health monitoring and damage detection is reviewed. Methods based on (a) elastic wave propagation and (b) electro-mechanical (E/M) impedance technique are cited and briefly discussed. The instrumentation of these specimens with piezoelectric active sensors is illustrated. The main detection strategies (E/M impedance for local area detection and wave propagation for wide area interrogation) are discussed. The signal processing and damage interpretation algorithms are tuned to the specific structural interrogation method used. In the high frequency E/M impedance approach, pattern recognition methods are used to compare impedance signatures taken at various time intervals and to identify damage presence and progression from the change in these signatures. In the wave propagation approach, the acousto- ultrasonic methods identifying additional reflection generated from the damage site and changes in transmission velocity and phase are used. Both approaches benefit from the use of artificial intelligence neural networks algorithms that can extract damage features based on a learning process. Design and fabrication of a set of structural specimens representative of aging aerospace structures is presented. Three built-up specimens, (pristine, with cracks, and with corrosion damage) are used. The specimen instrumentation with active sensors fabricated at the University of South Carolina is illustrated. Preliminary results obtained with the E/M impedance method on pristine and cracked specimens are presented.

Overlapping DNA Methylation Dynamics in Mouse Intestinal Cell Differentiation and Early Stages of Malignant Progression

PubMed Central

Forn, Marta; Díez-Villanueva, Anna; Merlos-Suárez, Anna; Muñoz, Mar; Lois, Sergi; Carriò, Elvira; Jordà, Mireia; Bigas, Anna; Batlle, Eduard; Peinado, Miguel A.

2015-01-01

Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart. PMID:25933092

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

PubMed

Langley, Raymond J; Tipper, Jennifer L; Bruse, Shannon; Baron, Rebecca M; Tsalik, Ephraim L; Huntley, James; Rogers, Angela J; Jaramillo, Richard J; O'Donnell, Denise; Mega, William M; Keaton, Mignon; Kensicki, Elizabeth; Gazourian, Lee; Fredenburgh, Laura E; Massaro, Anthony F; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Chris W; Kingsmore, Stephen F; Sopori, Mohan L; Perrella, Mark A; Choi, Augustine M K; Harrod, Kevin S

2014-08-15

Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis. Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers. The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82). A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.

The search for loci under selection: trends, biases and progress.

PubMed

Ahrens, Collin W; Rymer, Paul D; Stow, Adam; Bragg, Jason; Dillon, Shannon; Umbers, Kate D L; Dudaniec, Rachael Y

2018-03-01

Detecting genetic variants under selection using F ST outlier analysis (OA) and environmental association analyses (EAAs) are popular approaches that provide insight into the genetic basis of local adaptation. Despite the frequent use of OA and EAA approaches and their increasing attractiveness for detecting signatures of selection, their application to field-based empirical data have not been synthesized. Here, we review 66 empirical studies that use Single Nucleotide Polymorphisms (SNPs) in OA and EAA. We report trends and biases across biological systems, sequencing methods, approaches, parameters, environmental variables and their influence on detecting signatures of selection. We found striking variability in both the use and reporting of environmental data and statistical parameters. For example, linkage disequilibrium among SNPs and numbers of unique SNP associations identified with EAA were rarely reported. The proportion of putatively adaptive SNPs detected varied widely among studies, and decreased with the number of SNPs analysed. We found that genomic sampling effort had a greater impact than biological sampling effort on the proportion of identified SNPs under selection. OA identified a higher proportion of outliers when more individuals were sampled, but this was not the case for EAA. To facilitate repeatability, interpretation and synthesis of studies detecting selection, we recommend that future studies consistently report geographical coordinates, environmental data, model parameters, linkage disequilibrium, and measures of genetic structure. Identifying standards for how OA and EAA studies are designed and reported will aid future transparency and comparability of SNP-based selection studies and help to progress landscape and evolutionary genomics. © 2018 John Wiley & Sons Ltd.

10 CFR 600.250 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

13 CFR 143.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

15 CFR 24.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

14 CFR 1273.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi-differentiated Cell Populations in Dysplastic Colonic Crypts.

PubMed

Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio

2018-02-01

Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.

Prognostic and predictive biomarkers post curative intent therapy

PubMed Central

Feldman, Rebecca

2017-01-01

Large-scale screening trials have demonstrated that early diagnosis of lung cancer results in a significant reduction in lung cancer mortality. Despite improvements in detecting more lung cancers at early stages, the 5-year survival rates of lung cancers diagnosed before widespread disease is only 30–50%. High rates of recurrence, despite early diagnosis, suggest the need to improve treatment strategies based on the likelihood of recurrence in patient subsets, as well as explore the role of predictive markers for therapy selection in the adjuvant setting. In the era of personalized medicine, there have been a wide array of molecular alterations and signatures studied for their potential prognostic and predictive utility, however most have failed to translate into clinical tools. This review will discuss progress made in clinical management of lung cancer, and recent progress in the development of patient selection tools for the refinement of early stage lung cancers. PMID:29057234

Stable isotope signatures for characterising the biological stability of landfilled municipal solid waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wimmer, Bernhard, E-mail: bernhard.wimmer@ait.ac.at; Hrad, Marlies; Huber-Humer, Marion

Highlights: ► The isotopic signature of δ{sup 13}C-DIC of leachates is linked to the reactivity of MSW. ► Isotopic signatures of leachates depend on aerobic/anaerobic conditions in landfills. ► In situ aeration of landfills can be monitored by isotope analysis in leachate. ► The isotopic analysis of leachates can be used for assessing the stability of MSW. ► δ{sup 13}C-DIC of leachates helps to define the duration of landfill aftercare. - Abstract: Stable isotopic signatures of landfill leachates are influenced by processes within municipal solid waste (MSW) landfills mainly depending on the aerobic/anaerobic phase of the landfill. We investigated themore » isotopic signatures of δ{sup 13}C, δ{sup 2}H and δ{sup 18}O of different leachates from lab-scale experiments, lysimeter experiments and a landfill under in situ aeration. In the laboratory, columns filled with MSW of different age and reactivity were percolated under aerobic and anaerobic conditions. In landfill simulation reactors, waste of a 25 year old landfill was kept under aerobic and anaerobic conditions. The lysimeter facility was filled with mechanically shredded fresh waste. After starting of the methane production the waste in the lysimeter containments was aerated in situ. Leachate and gas composition were monitored continuously. In addition the seepage water of an old landfill was collected and analysed periodically before and during an in situ aeration. We found significant differences in the δ{sup 13}C-value of the dissolved inorganic carbon (δ{sup 13}C-DIC) of the leachate between aerobic and anaerobic waste material. During aerobic degradation, the signature of δ{sup 13}C-DIC was mainly dependent on the isotopic composition of the organic matter in the waste, resulting in a δ{sup 13}C-DIC of −20‰ to −25‰. The production of methane under anaerobic conditions caused an increase in δ{sup 13}C-DIC up to values of +10‰ and higher depending on the actual reactivity of the MSW. During aeration of a landfill the aerobic degradation of the remaining organic matter caused a decrease to a δ{sup 13}C-DIC of about −20‰. Therefore carbon isotope analysis in leachates and groundwater can be used for tracing the oxidation–reduction status of MSW landfills. Our results indicate that monitoring of stable isotopic signatures of landfill leachates over a longer time period (e.g. during in situ aeration) is a powerful and cost-effective tool for characterising the biodegradability and stability of the organic matter in landfilled municipal solid waste and can be used for monitoring the progress of in situ aeration.« less

Excellence in the Classroom

ERIC Educational Resources Information Center

Governor's Business Council (Texas), 2006

2006-01-01

Texas has made good progress in education since the school reform movement began in earnest 15 years ago. State test scores are up for all groups of students in all grades in all subjects. On the National Assessment of Educational Progress, Texas is close to the top in student performance in math, and has finally begun to make real progress in…