Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.

PubMed

Rojas-Ríos, Patricia; Chartier, Aymeric; Pierson, Stéphanie; Simonelig, Martine

2017-11-02

PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila , Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Synthesis and characterization of graphene quantum dots-silver nanocomposites

NASA Astrophysics Data System (ADS)

Vandana, M.; Ashokkumar, S. P.; Vijeth, H.; Niranjana, M.; Yesappa, L.; Devendrappa, H.

2018-04-01

A facile microwave assisted hydrothermal method is used to synthesise glucose derived water soluble crystalline graphene quantum dots (GQDs) andcitrate reduction method was used to synthesized silver nanoparticles (SNPs). The formation of graphene quantum dots-silver nanocomposites (GSC) was synthesized through a simple refluxing process and characterised using Fourier Transform Infrared (FT-IR) to study the chemical interaction, Surface morphology using FESEM, Optical properties were studied using UV-Visible spectroscopy. The absorption band shows at 249, 306 and 447 nm confirms the formation of GQDs and GSC. The electrochemical performance of GSC tested to determine the oxidation/reduction processes by cyclic voltammetry and linear sweep voltammetry.

CD22-Binding Synthetic Sialosides Regulate B Lymphocyte Proliferation Through CD22 Ligand-Dependent and Independent Pathways, and Enhance Antibody Production in Mice

PubMed Central

Matsubara, Naoko; Imamura, Akihiro; Yonemizu, Tatsuya; Akatsu, Chizuru; Yang, Hongrui; Ueki, Akiharu; Watanabe, Natsuki; Abdu-Allah, Hajjaj; Numoto, Nobutaka; Takematsu, Hiromu; Kitazume, Shinobu; Tedder, Thomas F.; Marth, Jamey D.; Ito, Nobutoshi; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto; Tsubata, Takeshi

2018-01-01

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands). Here, we developed synthetic sialosides GSC718 and GSC839 that bind to CD22 with high affinity (IC50 ~100 nM), and inhibit ligand binding of CD22. When B cells are activated by B cell antigen receptor (BCR) ligation, both GSC718 and GSC839 downregulate proliferation of B cells, and this regulation requires both CD22 and α2,6 sialic acids. This result suggests that these sialosides regulate BCR ligation-induced B cell activation by reversing endogenous ligand-mediated regulation of CD22. By contrast, GSC718 and GSC839 augment B cell proliferation induced by TLR ligands or CD40 ligation, and this augmentation requires CD22 but not α2,6 sialic acids. Thus, these sialosides appear to enhance B cell activation by directly suppressing the inhibitory function of CD22 independently of endogenous ligand-mediated regulation. Moreover, GSC839 augments B cell proliferation that depends on both BCR ligation and CD40 ligation as is the case for in vivo B cell responses to antigens, and enhanced antibody production to the extent comparable to CpG oligonuleotides or a small amount of alum. Although these known adjuvants induce production of the inflammatory cytokines or accumulation of inflammatory cells, CD22-binding sialosides do not. Thus, synthetic sialosides that bind to CD22 with high-affinity modulate B cell activation through endogenous ligand-dependent and independent pathways, and carry an adjuvant activity without inducing inflammation. PMID:29725338

CD22-Binding Synthetic Sialosides Regulate B Lymphocyte Proliferation Through CD22 Ligand-Dependent and Independent Pathways, and Enhance Antibody Production in Mice.

PubMed

Matsubara, Naoko; Imamura, Akihiro; Yonemizu, Tatsuya; Akatsu, Chizuru; Yang, Hongrui; Ueki, Akiharu; Watanabe, Natsuki; Abdu-Allah, Hajjaj; Numoto, Nobutaka; Takematsu, Hiromu; Kitazume, Shinobu; Tedder, Thomas F; Marth, Jamey D; Ito, Nobutoshi; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto; Tsubata, Takeshi

2018-01-01

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands). Here, we developed synthetic sialosides GSC718 and GSC839 that bind to CD22 with high affinity (IC 50 ~100 nM), and inhibit ligand binding of CD22. When B cells are activated by B cell antigen receptor (BCR) ligation, both GSC718 and GSC839 downregulate proliferation of B cells, and this regulation requires both CD22 and α2,6 sialic acids. This result suggests that these sialosides regulate BCR ligation-induced B cell activation by reversing endogenous ligand-mediated regulation of CD22. By contrast, GSC718 and GSC839 augment B cell proliferation induced by TLR ligands or CD40 ligation, and this augmentation requires CD22 but not α2,6 sialic acids. Thus, these sialosides appear to enhance B cell activation by directly suppressing the inhibitory function of CD22 independently of endogenous ligand-mediated regulation. Moreover, GSC839 augments B cell proliferation that depends on both BCR ligation and CD40 ligation as is the case for in vivo B cell responses to antigens, and enhanced antibody production to the extent comparable to CpG oligonuleotides or a small amount of alum. Although these known adjuvants induce production of the inflammatory cytokines or accumulation of inflammatory cells, CD22-binding sialosides do not. Thus, synthetic sialosides that bind to CD22 with high-affinity modulate B cell activation through endogenous ligand-dependent and independent pathways, and carry an adjuvant activity without inducing inflammation.

Individual employee's perceptions of " Group-level Safety Climate" (supervisor referenced) versus " Organization-level Safety Climate" (top management referenced): Associations with safety outcomes for lone workers.

PubMed

Huang, Yueng-Hsiang; Lee, Jin; McFadden, Anna C; Rineer, Jennifer; Robertson, Michelle M

2017-01-01

Research has shown that safety climate is among the strongest predictors of safety behavior and safety outcomes in a variety of settings. Previous studies have established that safety climate is a multi-faceted construct referencing multiple levels of management within a company, most generally: the organization level (employee perceptions of top management's commitment to and prioritization of safety) and group level (employee perceptions of direct supervisor's commitment to and prioritization of safety). Yet, no research to date has examined the potential interaction between employees' organization-level safety climate (OSC) and group-level safety climate (GSC) perceptions. Furthermore, prior research has mainly focused on traditional work environments in which supervisors and workers interact in the same location throughout the day. Little research has been done to examine safety climate with regard to lone workers. The present study aims to address these gaps by examining the relationships between truck drivers' (as an example of lone workers) perceptions of OSC and GSC, both potential linear and non-linear relationships, and how these predict important safety outcomes. Participants were 8095 truck drivers from eight trucking companies in the United States with an average response rate of 44.8%. Results showed that employees' OSC and GSC perceptions are highly correlated (r= 0.78), but notable gaps between the two were observed for some truck drivers. Uniquely, both OSC and GSC scores were found to have curvilinear relationships with safe driving behavior, and both scores were equally predictive of safe driving behavior. Results also showed the two levels of climate significantly interacted with one another to predict safety behavior such that if either the OSC or GSC scores were low, the other's contribution to safety behavior became stronger. These findings suggest that OSC and GSC may function in a compensatory manner and promote safe driving behavior even when either OSC or GSC scores are low. The results of this study provide critical insight into the supplementary interaction between perceptions of OSC and GSC. Recommendations for future research, as well as practical recommendations for organizational intervention, are discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

TLR9 is critical for glioma stem cell maintenance and targeting.

PubMed

Herrmann, Andreas; Cherryholmes, Gregory; Schroeder, Anne; Phallen, Jillian; Alizadeh, Darya; Xin, Hong; Wang, Tianyi; Lee, Heehyoung; Lahtz, Christoph; Swiderski, Piotr; Armstrong, Brian; Kowolik, Claudia; Gallia, Gary L; Lim, Michael; Brown, Christine; Badie, Behnam; Forman, Stephen; Kortylewski, Marcin; Jove, Richard; Yu, Hua

2014-09-15

Understanding supports for cancer stem-like cells in malignant glioma may suggest therapeutic strategies for their elimination. Here, we show that the Toll-like receptor TLR9 is elevated in glioma stem-like cells (GSC) in which it contributes to glioma growth. TLR9 overexpression is regulated by STAT3, which is required for GSC maintenance. Stimulation of TLR9 with a CpG ligand (CpG ODN) promoted GSC growth, whereas silencing TLR9 expression abrogated GSC development. CpG-ODN treatment induced Frizzled4-dependent activation of JAK2, thereby activating STAT3. Targeted delivery of siRNA into GSC was achieved via TLR9 using CpG-siRNA conjugates. Through local or systemic treatment, administration of CpG-Stat3 siRNA to silence STAT3 in vivo reduced GSC along with glioma growth. Our findings identify TLR9 as a functional marker for GSC and a target for the delivery of efficacious therapeutics for glioma treatment. Cancer Res; 74(18); 5218-28. ©2014 AACR. ©2014 American Association for Cancer Research.

Sleep-related memory consolidation in primary insomnia.

PubMed

Nissen, Christoph; Kloepfer, Corinna; Feige, Bernd; Piosczyk, Hannah; Spiegelhalder, Kai; Voderholzer, Ulrich; Riemann, Dieter

2011-03-01

It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n=86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep ('sleep condition' in PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory. © 2010 European Sleep Research Society.

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle.

PubMed

Kantarci, Husniye; Gerberding, Andrea; Riley, Bruce B

2016-11-01

Neurons of the Statoacoustic Ganglion (SAG), which innervate the inner ear, originate as neuroblasts in the floor of the otic vesicle and subsequently delaminate and migrate toward the hindbrain before completing differentiation. In all vertebrates, locally expressed Fgf initiates SAG development by inducing expression of Neurogenin1 (Ngn1) in the floor of the otic vesicle. However, not all Ngn1-positive cells undergo delamination, nor has the mechanism controlling SAG delamination been elucidated. Here we report that Goosecoid (Gsc), best known for regulating cellular dynamics in the Spemann organizer, regulates delamination of neuroblasts in the otic vesicle. In zebrafish, Fgf coregulates expression of Gsc and Ngn1 in partially overlapping domains, with delamination occurring primarily in the zone of overlap. Loss of Gsc severely inhibits delamination, whereas overexpression of Gsc greatly increases delamination. Comisexpression of Ngn1 and Gsc induces ectopic delamination of some cells from the medial wall of the otic vesicle but with a low incidence, suggesting the action of a local inhibitor. The medial marker Pax2a is required to restrict the domain of gsc expression, and misexpression of Pax2a is sufficient to block delamination and fully suppress the effects of Gsc The opposing activities of Gsc and Pax2a correlate with repression or up-regulation, respectively, of E-cadherin (cdh1). These data resolve a genetic mechanism controlling delamination of otic neuroblasts. The data also elucidate a developmental role for Gsc consistent with a general function in promoting epithelial-to-mesenchymal transition (EMT).

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

PubMed Central

Kantarci, Husniye; Gerberding, Andrea; Riley, Bruce B.

2016-01-01

Neurons of the Statoacoustic Ganglion (SAG), which innervate the inner ear, originate as neuroblasts in the floor of the otic vesicle and subsequently delaminate and migrate toward the hindbrain before completing differentiation. In all vertebrates, locally expressed Fgf initiates SAG development by inducing expression of Neurogenin1 (Ngn1) in the floor of the otic vesicle. However, not all Ngn1-positive cells undergo delamination, nor has the mechanism controlling SAG delamination been elucidated. Here we report that Goosecoid (Gsc), best known for regulating cellular dynamics in the Spemann organizer, regulates delamination of neuroblasts in the otic vesicle. In zebrafish, Fgf coregulates expression of Gsc and Ngn1 in partially overlapping domains, with delamination occurring primarily in the zone of overlap. Loss of Gsc severely inhibits delamination, whereas overexpression of Gsc greatly increases delamination. Comisexpression of Ngn1 and Gsc induces ectopic delamination of some cells from the medial wall of the otic vesicle but with a low incidence, suggesting the action of a local inhibitor. The medial marker Pax2a is required to restrict the domain of gsc expression, and misexpression of Pax2a is sufficient to block delamination and fully suppress the effects of Gsc. The opposing activities of Gsc and Pax2a correlate with repression or up-regulation, respectively, of E-cadherin (cdh1). These data resolve a genetic mechanism controlling delamination of otic neuroblasts. The data also elucidate a developmental role for Gsc consistent with a general function in promoting epithelial-to-mesenchymal transition (EMT). PMID:27791112

Modification of Tet1 and histone methylation dynamics in dairy goat male germline stem cells.

PubMed

Zheng, Liming; Zhai, Yuanxin; Li, Na; Wu, Chongyang; Zhu, Haijing; Wei, Zhuying; Bai, Chunling; Li, Guangpeng; Hua, Jinlian

2016-04-01

Tet (ten-eleven translocation) protein 1 is a key enzyme for DNA demethylation, which modulates DNA methylation and gene transcription. DNA methylation and histone methylation are critical elements in self-renewal of male germline stem cells (mGSCs) and spermatogenesis. mGSCs are the only type of adult stem cells able to achieve intergenerational transfer of genetic information, which is accomplished through differentiated sperm cells. However, numerous epigenetic obstacles including incomplete DNA methylation and histone methylation dynamics make establishment of stable livestock mGSC cell lines difficult. The present study was conducted to detect effects of DNA methylation and histone methylation dynamics in dairy goat mGSCs self-renewal and proliferation, through overexpression of Tet1. An immortalized dairy goat mGSC cell line bearing mouse Tet1 (mTet1) gene was screened and characteristics of the cells were assayed by quantitative real-time PCR (qRT-PCR), immunofluorescence assay, western blotting, fluorescence activated cell sorting (FACS) and use of the cell counting kit (CCK8) assay. The screened immortalized dairy goat mGSC cell line bearing mTet1, called mGSC-mTet1 cells was treated with optimal doxycycline (Dox) concentration to maintain Tet1 gene expression. mGSC-mTet1 cells proliferated at a significantly greater rate than wild-type mGSCs, and mGSCs-specific markers such as proliferating cell nuclear antigen (PCNA), cyclinD1 (CCND1), GDNF family receptor alpha 1 (Gfra1) and endogenic Tet1, Tet2 were upregulated. The cells exhibited not only reduction in level of histone methylation but also changes in nuclear location of that methylation marker. While H3K9me3 was uniformly distributed throughout the nucleus of mGSC-mTet1 cells, it was present in only particular locations in mGSCs. H3K27me3 was distributed surrounding the edges of nuclei of mGSC-mTet1 cells, while it was uniformly distributed throughout nuclei of mGSCs. Our results conclusively demonstrate that modification of mGSCs with mTet1 affected mGSC maintenance and seemed to promote establishment of stable goat mGSC cell lines. Taken together, our data suggest that Tet1 had novel and dynamic roles for regulating maintenance of pluripotency and proliferation of mGSCs by forming complexes with PCNA and histone methylation dynamics. This may provide new solutions for mGSCs stability and livestock mGSC cell line establishment. © 2016 John Wiley & Sons Ltd.

First orbital solution and evolutionary state for the newly discovered eclipsing binaries USNO-B1.0 1091-0130715 and GSC-03449-0680

NASA Astrophysics Data System (ADS)

Elkhateeb, M. M.; Nouh, M. I.; Nelson, R. H.

2015-02-01

A first photometric study for the newly discovered systems USNO-B1.0 1091-0130715 and GSC-03449-0680 was carried out by means of recent a windows interface version of the Wilson and Devinney code based on model atmospheres by Kurucz (1993). The accepted models reveal some absolute parameters for both systems, which are used in deriving the spectral type of the system components and their evolutionary status. Distances to each systems and physical properties were estimated. Comparisons of the computed physical parameters with stellar models are discussed. The components of the system USNO-B1.0 1091-0130715 and the primary of the system GSC-03449-0680 are found to be on or near the ZAMS track, while the secondary of GSC-03449-0680 system found to be severely under luminous and too cool compared to its ZAMS mass.

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

Radchenko, Valery; Meyer, Catherine Anne Louise; Engle, Jonathan Ward

Scandium-44 g (half-life 3.97 h) shows promise for positron emission tomography (PET) imaging of longer biological processes than that of the current gold standard, 18F, due to its favorable decay parameters. One source of 44gSc is the long-lived parent nuclide 44Ti (half-life 60.0 a). A 44Ti/ 44gSc generator would have the ability to provide radionuclidically pure 44gSc on a daily basis. The production of 44Ti via the 45Sc(p,2n) reaction requires high proton beam currents and long irradiation times. Recovery and purification of no-carrier added (nca) 44Ti from scandium metal targets involves complex separation chemistry. In this study, separation systems basedmore » on solid phase extraction chromatography were investigated, including branched diglycolamide (BDGA) resin and hydroxamate based ZR resin. Lastly, results indicate that ZR resin in HCl media represents an effective 44Ti/ 44gSc separation system.« less

Vier suedliche chromosphaerisch aktive Sterne in der ASAS-3 Datenbank entdeckt

NASA Astrophysics Data System (ADS)

Bernhard, Klaus; Huemmerich, Stefan

2014-11-01

Four southern chromospherically active stars are presented, which were found in the ASAS-3 database (GSC 08590-01193, GSC 08962-00532, GSC 08677-00344 and GSC 08724-01284). Candidates were selected from Table 4 of Fresneau and Osborn (2009), which identifies candidate active stars that have been found by cross-correlating entries from the Variability Sample Catalogue of the Sydney Observatory Galactic Survey (SOGS) with X-ray sources from the ROSAT All Sky Survey (for more details, see loc. cit.).

Meeting report: GSC M5 roundtable at the 13th International Society for Microbial Ecology meeting in Seattle, WA, USA August 22-27, 2010

PubMed Central

Gilbert, Jack A.; Meyer, Folker; Knight, Rob; Field, Dawn; Kyrpides, Nikos; Yilmaz, Pelin; Wooley, John

2010-01-01

This report summarizes the proceedings of the Metagenomics, Metadata, Metaanalysis, Models and Metainfrastructure (M5) Roundtable at the 13th International Society for Microbial Ecology Meeting in Seattle, WA, USA August 22-27, 2010. The Genomic Standards Consortium (GSC) hosted this meeting as a community engagement exercise to describe the GSC to the microbial ecology community during this important international meeting. The roundtable included five talks given by members of the GSC, and was followed by audience participation in the form of a roundtable discussion. This report summarizes this event. Further information on the GSC and its range of activities can be found at http://www.gensc.org. PMID:21304725

Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediation

PubMed Central

Yun, Jiae; Malvankar, Nikhil S; Ueki, Toshiyuki; Lovley, Derek R

2016-01-01

Studies with pure cultures of dissimilatory metal-reducing microorganisms have demonstrated that outer-surface c-type cytochromes are important electron transfer agents for the reduction of metals, but previous environmental proteomic studies have typically not recovered cytochrome sequences from subsurface environments in which metal reduction is important. Gel-separation, heme-staining and mass spectrometry of proteins in groundwater from in situ uranium bioremediation experiments identified a putative c-type cytochrome, designated Geobacter subsurface c-type cytochrome A (GscA), encoded within the genome of strain M18, a Geobacter isolate previously recovered from the site. Homologs of GscA were identified in the genomes of other Geobacter isolates in the phylogenetic cluster known as subsurface clade 1, which predominates in a diversity of Fe(III)-reducing subsurface environments. Most of the gscA sequences recovered from groundwater genomic DNA clustered in a tight phylogenetic group closely related to strain M18. GscA was most abundant in groundwater samples in which Geobacter sp. predominated. Expression of gscA in a strain of Geobacter sulfurreducens that lacked the gene for the c-type cytochrome OmcS, thought to facilitate electron transfer from conductive pili to Fe(III) oxide, restored the capacity for Fe(III) oxide reduction. Atomic force microscopy provided evidence that GscA was associated with the pili. These results demonstrate that a c-type cytochrome with an apparent function similar to that of OmcS is abundant when Geobacter sp. are abundant in the subsurface, providing insight into the mechanisms for the growth of subsurface Geobacter sp. on Fe(III) oxide and suggesting an approach for functional analysis of other Geobacter proteins found in the subsurface. PMID:26140532

Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediation.

PubMed

Yun, Jiae; Malvankar, Nikhil S; Ueki, Toshiyuki; Lovley, Derek R

2016-02-01

Studies with pure cultures of dissimilatory metal-reducing microorganisms have demonstrated that outer-surface c-type cytochromes are important electron transfer agents for the reduction of metals, but previous environmental proteomic studies have typically not recovered cytochrome sequences from subsurface environments in which metal reduction is important. Gel-separation, heme-staining and mass spectrometry of proteins in groundwater from in situ uranium bioremediation experiments identified a putative c-type cytochrome, designated Geobacter subsurface c-type cytochrome A (GscA), encoded within the genome of strain M18, a Geobacter isolate previously recovered from the site. Homologs of GscA were identified in the genomes of other Geobacter isolates in the phylogenetic cluster known as subsurface clade 1, which predominates in a diversity of Fe(III)-reducing subsurface environments. Most of the gscA sequences recovered from groundwater genomic DNA clustered in a tight phylogenetic group closely related to strain M18. GscA was most abundant in groundwater samples in which Geobacter sp. predominated. Expression of gscA in a strain of Geobacter sulfurreducens that lacked the gene for the c-type cytochrome OmcS, thought to facilitate electron transfer from conductive pili to Fe(III) oxide, restored the capacity for Fe(III) oxide reduction. Atomic force microscopy provided evidence that GscA was associated with the pili. These results demonstrate that a c-type cytochrome with an apparent function similar to that of OmcS is abundant when Geobacter sp. are abundant in the subsurface, providing insight into the mechanisms for the growth of subsurface Geobacter sp. on Fe(III) oxide and suggesting an approach for functional analysis of other Geobacter proteins found in the subsurface.

Differences in the management of amblyopia between European countries

PubMed Central

Tan, J H Y; Thompson, J R; Gottlob, I

2003-01-01

Background: Amblyopia treatment is not standardised and differences between centres and countries have not been systematically investigated. This survey compares the different patterns of orthoptic treatment of amblyopia in the United Kingdom (UK) and three German speaking countries (GSC). Methods: Questionnaires were sent to orthoptists in the UK and the GSC asking for their preferred choices of treatment of amblyopia between the ages of 6 months to 10 years. Results: The following significant differences in management of amblyopia were found: (1) the number of hours of occlusion per week was higher in the GSC, p<0.0001, (2) orthoptists in the GSC treat amblyopia up to an older age. Orthoptists in the GSC and in the UK predicted similar treatment outcomes. Conclusion: Orthoptists in the GSC usually treat patients more intensively and for longer, while the prediction of visual outcome does not differ significantly between countries. These results highlight the lack of standardisation in the treatment of the various types of amblyopia. PMID:12598440

GSC 02505-00411: A new delta Sct star in the field of RZ LMi

NASA Astrophysics Data System (ADS)

Ishioka, R.; Kokumbaeva, R.

2017-04-01

We present the time series analysis of CCD photometry from ``EAST'' Zeiss-1000 telescope at Tien-Shan Astronomical Observatory (Almaty, Kazakhstan) for GSC 02505-00411. GSC 02505-00411 is a new multi-frequency delta Scuti variable with a primary frequency of 43.84 c/d.

Genomic standards consortium projects.

PubMed

Field, Dawn; Sterk, Peter; Kottmann, Renzo; De Smet, J Wim; Amaral-Zettler, Linda; Cochrane, Guy; Cole, James R; Davies, Neil; Dawyndt, Peter; Garrity, George M; Gilbert, Jack A; Glöckner, Frank Oliver; Hirschman, Lynette; Klenk, Hans-Peter; Knight, Rob; Kyrpides, Nikos; Meyer, Folker; Karsch-Mizrachi, Ilene; Morrison, Norman; Robbins, Robert; San Gil, Inigo; Sansone, Susanna; Schriml, Lynn; Tatusova, Tatiana; Ussery, Dave; Yilmaz, Pelin; White, Owen; Wooley, John; Caporaso, Gregory

2014-06-15

The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

MAXI/GSC detection of a possible new X-ray nova MAXI J1621-501 on the galactic plane

NASA Astrophysics Data System (ADS)

Hashimoto, T.; Negoro, H.; Ueno, S.; Tomida, H.; Ishikawa, M.; Sugawara, Y.; Isobe, N.; Shimomukai, R.; Mihara, T.; Sugizaki, M.; Nakahira, S.; Iwakiri, W.; Shidatsu, M.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugita, S.; Yoshii, T.; Tachibana, Y.; Harita, S.; Morita, K.; Yoshida, A.; Sakamoto, T.; Serino, M.; Kawakubo, Y.; Kitaoka, Y.; Tsunemi, H.; Yoneyama, T.; Nakajima, M.; Kawase, T.; Sakamaki, A.; Ueda, Y.; Hori, T.; Tanimoto, A.; Oda, S.; Tsuboi, Y.; Nakamura, Y.; Sasaki, R.; Kawai, H.; Yamauchi, M.; Hanyu, C.; Hidaka, K.; Kawamuro, T.; Yamaoka, K.

2017-10-01

The MAXI/GSC nova alert system triggered on a bright uncatalogued X-ray transient source at 05:45 UT on 2017 October 19. Using GSC camera GSC_5 data of 4 scan transits from 04:12 to 08:50, we obtain the source position at (R.A., Dec) = (245.260 deg, -50.185 deg) = (16 21 02, -50 11 06) (J2000) with a statistical 90% C.L. elliptical error region with long and short radii of 0.23 deg and 0.22 deg, respectively.

Soil water availability and capacity of nitrogen accumulation influence variations of intrinsic water use efficiency in rice.

PubMed

Xue, Wei; Nay-Htoon, Bhone; Lindner, Steve; Dubbert, Maren; Otieno, Dennis; Ko, Jonghan; Werner, Christiane; Tenhunen, John

2016-04-01

Leaf intrinsic water use efficiency (WUEi) coupling maximum assimilation rate (Amax) and transpirable water lost via stomatal conductance (gsc) has been gaining increasing concern in sustainable crop production. Factors that influence leaf Amax and WUEi in rice (Oryza sativa L. cv Unkang) at flooding and rainfed conditions were evaluated. Positive correlations for leaf nitrogen content (Nm) and maximum carboxylation rate (Vcmax), for nitrogen allocation in Rubisco enzymes and mesophyll conductance (gm) were evident independent of cropping cultures. Rainfed rice exhibited enriched canopy leaf average Nm resulting in higher Amax, partially supporting improved leaf WUEi. Maximum WUEi (up to 0.14 μmol mmol(-1)) recorded in rainfed rice under drought conditions resulted from increasing gm/gsc ratio while at cost of significant decline in Amax due to hydraulically constrained gsc. Amax sensitivity related to gsc which was regulated by plant hydraulic conductance. WUEi was tightly correlated to Vcmax/gsc and gm/gsc ratios across the paddy and rainfed not to light environment, morphological and physiological traits, highlighting enhance capacity of Nm accumulation in rainfed rice with gsc at moderately high level similar to paddy rice facilitate optimization in Amax and WUEi while, is challenged by drought-vulnerable plant hydraulic conductance. Copyright © 2016 Elsevier GmbH. All rights reserved.

Seamount Lineaments of the Northern Galápagos and Plume-ridge Interaction

NASA Astrophysics Data System (ADS)

Cushman, W.; Harpp, K. S.; Kurz, M. D.; Geist, D.; Mittelstaedt, E. L.; Fornari, D. J.; Soule, S.; R/v Melville Mv1007 Flamingo Scientific Team

2010-12-01

The Northern Galápagos Province (NGP) is located between the Galápagos Archipelago and the Galápagos Spreading Center (GSC). There are 3 volcanic lineaments in the NGP, trending NW/SE. The lineaments’ origins remain enigmatic, but may provide information about plume-ridge interaction. In 2010, the R/V Melville MV1007 Cruise employed EM122 multibeam bathymetry, MR1 sidescan sonar, and dredging to study the area. The western lineament, the Wolf-Darwin Lineament (WDL), intersects the GSC at ~92°10’W and is the largest of the 3. The WDL is ~190km long and has 6 main volcanic centers, with many smaller satellite vents. The Central Lineament (CL) intersects the GSC at ~91°48’W and is ~60 km long with 4 major seamounts. The largest is roughly 2/3 the volume of the WDL’s smallest seamount. The Eastern Lineament (EL) intersects the GSC at ~91°16’W and is ~100km long. The EL includes 5 major seamounts with intermediate volumes. From N to S, the edifices in the WDL and the EL become more elongate, suggesting greater deviatoric stresses away from the ridge. The elongation is more pronounced in WDL seamounts than on those in the EL. The bathymetric footprints of seamounts on the N end of both lineaments are more symmetrical, as are all those of the CL. Seamounts with circular bases are probably monogenetic, with limited ranges of Mg#, phenocryst content, and incompatible trace element (ITE) concentrations. Most have single vents. The larger elongate seamounts have multiple vents and wider compositional ranges, likely the result of polygenetic eruptive histories. Lavas erupted along the lineaments have ITE ratios ranging between Galápagos Plume and depleted upper mantle sources, suggesting that mixing between the 2 sources occurs in the NGP. No seamount is more enriched than GSC axial lavas from within the study area, and no systematic gradient exists along strike of any of the lineaments, indicating that mixing between the plume and ridge is not simply progressive. The CL is the least plume-like, with the EL generally exhibiting more and the WDL the most plume contributions. The 3He/4He ratios along the lineaments are MORB-like, with a slight increase S along the WDL and EL. The Sm/Yb for WDL lavas increase southward, which may reflect increasing depth of melt generation in response to thickening lithosphere away from the GSC. The increase is more pronounced S of a pseudofault that intersects the WDL. Morgan (1978) proposed that the WDL is a channel along which plume material reaches the GSC; more recent models have been proposed for the lineaments in which plume material is transported to the GSC via ‘fingers’ that act as conduits. Data from the lineaments are inconsistent with both hypotheses, which predict increasing plume influence with distance from the GSC. An alternative hypothesis invokes stresses induced on the NGP by the GSC transform fault at ~90°50’W. These stresses create weak zones in the lithosphere along which plume-contaminated mantle is erupted to form lineaments. This hypothesis predicts no channeling of plume material to the GSC, but rather that the lineaments are the result of dispersed, point source eruptions tapping the heterogeneous mantle.

Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic.

PubMed

Teplyuk, Nadiya M; Uhlmann, Erik J; Gabriely, Galina; Volfovsky, Natalia; Wang, Yang; Teng, Jian; Karmali, Priya; Marcusson, Eric; Peter, Merlene; Mohan, Athul; Kraytsberg, Yevgenya; Cialic, Ron; Chiocca, E Antonio; Godlewski, Jakub; Tannous, Bakhos; Krichevsky, Anna M

2016-03-01

MicroRNA-10b (miR-10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Although several miR-10b targets have been identified previously, the common mechanism conferring the miR-10b-sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5'UTRs of its target genes, including MBNL1-3, SART3, and RSRC1. We have further assessed the inhibition of miR-10b in intracranial human GSC-derived xenograft and murine GL261 allograft models in athymic and immunocompetent mice. Three delivery routes for the miR-10b antisense oligonucleotide inhibitors (ASO), direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections, have been explored. In all cases, the treatment with miR-10b ASO led to targets' derepression, and attenuated growth and progression of established intracranial GBM. No significant systemic toxicity was observed upon ASO administration by local or systemic routes. Our results indicate that miR-10b is a promising candidate for the development of targeted therapies against all GBM subtypes. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

PubMed

Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

PubMed Central

Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

2016-01-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

The CCR4 Deadenylase Acts with Nanos and Pumilio in the Fine-Tuning of Mei-P26 Expression to Promote Germline Stem Cell Self-Renewal

PubMed Central

Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

2013-01-01

Summary Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation. PMID:24286029

The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal.

PubMed

Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

2013-01-01

Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation.

Carbon Raman Spectroscopy of 36 Inter-Planetary Dust Particles

NASA Technical Reports Server (NTRS)

Busemann, H.; Nittler, L. R.; Davidson, J.; Franchi, I. A.; Messenger, S.; Nakamura-Messenger, K.; Palma, R. L.; Pepin, R. O.

2009-01-01

Carbon Raman spectroscopy is a useful tool to determine the degree of order of organic material (OM) in extra-terrestrial matter. As shown for meteoritic OM [e.g., 2], peak parameters of D and G bands are a measure of thermal alteration, causing graphitization (order), and amorphization, e.g. during protoplanetary irradiation, causing disorder. Th e most pristine interplanetary dust particles (IDPs) may come from comets. However, their exact provenance is unknown. IDP collection during Earth?s passage through comet Grigg-Skjellerup?s dust stream ("GSC" collectors) may increase the probability of collecting fresh IDPs from a known, cometary source. We used Raman spectroscopy to compare 21 GSC-IDPs with 15 IDPs collected at different periods, and found that the variation among GSC-IDPs is larger than among non-GSC IDPs, with the most primitive IDPs being mostly GSC-IDPs.

Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors.

PubMed

Xie, Ting

2013-01-01

In the Drosophila ovary, germline stem cells (GSCs) physically interact with their niche composed of terminal filament cells, cap cells, and possibly GSC-contacting escort cells (ECs). A GSC divides to generate a self-renewing stem cell that remains in the niche and a differentiating daughter that moves away from the niche. The GSC niche provides a bone morphogenetic protein (BMP) signal that maintains GSC self-renewal by preventing stem cell differentiation via repression of the differentiation-promoting gene bag of marbles (bam). In addition, it expresses E-cadherin, which mediates cell adhesion for anchoring GSCs in the niche, enabling continuous self-renewal. GSCs themselves also express different classes of intrinsic factors, including signal transducers, transcription factors, chromatin remodeling factors, translation regulators, and miRNAs, which control self-renewal by strengthening interactions with the niche and repressing various differentiation pathways. Differentiated GSC daughters, known as cystoblasts (CBs), also express distinct classes of intrinsic factors to inhibit self-renewal and promote germ cell differentiation. Surprisingly, GSC progeny are also dependent on their surrounding ECs for proper differentiation at least partly by preventing BMP from diffusing to the differentiated germ cell zone and by repressing ectopic BMP expression. Therefore, both GSC self-renewal and CB differentiation are controlled by collaborative actions of extrinsic signals and intrinsic factors. Copyright © 2012 Wiley Periodicals, Inc.

Onufrienko holds a Grab Sample Container (GSC) in the SM during Expedition Four

NASA Image and Video Library

2002-05-23

ISS004-E-12368 (23 May 2002) --- Cosmonaut Yury I. Onufrienko, Expedition Four mission commander representing Rosaviakosmos, holds a Grab Sample Container (GSC) in the Zvezda Service Module on the International Space Station (ISS). The GSC is used to take air samples in various modules as part of environmental quality control.

Aging and insulin signaling differentially control normal and tumorous germline stem cells.

PubMed

Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

2015-02-01

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.

PubMed

Brown, Christine E; Starr, Renate; Aguilar, Brenda; Shami, Andrew F; Martinez, Catalina; D'Apuzzo, Massimo; Barish, Michael E; Forman, Stephen J; Jensen, Michael C

2012-04-15

To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation. A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo. We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice. Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. ©2012 AACR.

m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

PubMed Central

Cui, Qi; Shi, Hailing; Ye, Peng; Li, Li; Qu, Qiuhao; Sun, Guoqiang; Sun, Guihua; Lu, Zhike; Huang, Yue; Yang, Cai-Guang; Riggs, Arthur D.

2017-01-01

Summary RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma. PMID:28297667

Separation of 44Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of 44Ti/ 44Sc generator system

DOE PAGES

Radchenko, Valery; Meyer, Catherine Anne Louise; Engle, Jonathan Ward; ...

2016-11-24

Scandium-44 g (half-life 3.97 h) shows promise for positron emission tomography (PET) imaging of longer biological processes than that of the current gold standard, 18F, due to its favorable decay parameters. One source of 44gSc is the long-lived parent nuclide 44Ti (half-life 60.0 a). A 44Ti/ 44gSc generator would have the ability to provide radionuclidically pure 44gSc on a daily basis. The production of 44Ti via the 45Sc(p,2n) reaction requires high proton beam currents and long irradiation times. Recovery and purification of no-carrier added (nca) 44Ti from scandium metal targets involves complex separation chemistry. In this study, separation systems basedmore » on solid phase extraction chromatography were investigated, including branched diglycolamide (BDGA) resin and hydroxamate based ZR resin. Lastly, results indicate that ZR resin in HCl media represents an effective 44Ti/ 44gSc separation system.« less

Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster

PubMed Central

Matsuoka, Shinya; Armstrong, Alissa R.; Sampson, Leesa L.; Laws, Kaitlin M.; Drummond-Barbosa, Daniela

2017-01-01

Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism–stem cell link as an important area of investigation in other stem cell systems. PMID:28396508

Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster.

PubMed

Matsuoka, Shinya; Armstrong, Alissa R; Sampson, Leesa L; Laws, Kaitlin M; Drummond-Barbosa, Daniela

2017-06-01

Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism-stem cell link as an important area of investigation in other stem cell systems. Copyright © 2017 by the Genetics Society of America.

Green synthesis of palm oil mill effluent-based graphenic adsorbent for the treatment of dye-contaminated wastewater.

PubMed

Teow, Yeit Haan; Nordin, Nadzirah Ilyiani; Mohammad, Abdul Wahab

2018-05-12

Textile wastewater contains methylene blue (MB), a major coloring agent in textile industry. Activated carbon (AC) is the most widely used adsorbent in removing dyes from industrial wastewater. However, high production cost of AC is the major obstacle for its wide application in dye wastewater treatment. In this study, a sustainable approach in synthesizing graphenic adsorbent from palm oil mill effluent (POME), a potential carbonaceous source, has been explored. This new development in adsorption technique is considered as green synthesis as it does not require any binder during the synthesis process, and at the same time, it helps to solve the bottleneck of palm oil industry as POME is the main cause contributed to Malaysia's water pollution problem. The synthesized GSC was characterized through XRD, FESEM, and EDX. The adsorption performance of the synthesized GSC was evaluated by adsorption of MB. The effect of initial concentration of synthetic MB solution (1-20 mg/L) and weight of GSC (5-20 g) were investigated. A remarkable change in color of synthetic MB solution from blue to crystal clear was observed at the end of adsorption study. High efficiency of the synthesized GSC for dye-contaminated wastewater treatment is concluded.

Reversing glioma malignancy: a new look at the role of antidepressant drugs as adjuvant therapy for glioblastoma multiforme.

PubMed

Bielecka-Wajdman, Anna M; Lesiak, Marta; Ludyga, Tomasz; Sieroń, Aleksander; Obuchowicz, Ewa

2017-06-01

The role of glioma stem cells (GSCs) in cancer progression is currently debated; however, it is hypothesised that this subpopulation is partially responsible for therapeutic resistance observed in glioblastoma multiforme (GBM). Recent studies have shown that the current treatments not only fail to eliminate the GSC population but even promote GSCs through reprogramming of glioma non-stem cells to stem cells. Since the standard GBM treatment often requires supplementation with adjuvant drugs such as antidepressants, their role in the regulation of the heterogeneous nature of GSCs needs evaluation. We examined the effects of imipramine, amitriptyline, fluoxetine, mirtazapine, agomelatine, escitalopram, and temozolomide on the phenotypic signature (CD44, Ki67, Nestin, Sox1, and Sox2 expression) of GSCs isolated from a human T98G cell line. These drugs were examined in several models of hypoxia (1% oxygen, 2.5% oxygen, and a hypoxia-reoxygenation model) as compared to the standard laboratory conditions (20% oxygen). We report that antidepressant drugs, particularly imipramine and amitriptyline, modulate plasticity, silence the GSC profile, and partially reverse the malignant phenotype of GBM. Moreover, we observed that, in contrast to temozolomide, these tricyclic antidepressants stimulated viability and mitochondrial activity in normal human astrocytes. The ability of phenotype switching from GSC to non-GSC as stimulated by antidepressants (primarily imipramine and amitriptyline) sheds new light on the heterogeneous nature of GSC, as well as the role of antidepressants in adjuvant GBM therapy.

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa).

PubMed

Barfield, Sarah; Aglyamova, Galina V; Matz, Mikhail V

2016-01-13

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. © 2016 The Author(s).

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa)

PubMed Central

Barfield, Sarah; Aglyamova, Galina V.; Matz, Mikhail V.

2016-01-01

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. PMID:26763699

Guide star catalogue data retrieval software 2

NASA Technical Reports Server (NTRS)

Smirnov, O. M.; Malkov, O. YU.

1992-01-01

The Guide Star Catalog (GSC), being the largest astronomical catalog to date, is widely used by the astronomical community for all sorts of applications, such as statistical studies of certain sky regions, searches for counterparts to observational phenomena, and generation of finder charts. It's format (2 CD-ROM's) requires minimum hardware and is ideally suited for all sorts of conditions, especially observations. Unfortunately, the actual GSC data is not easily accessible. It takes the form of FITS tables, and the coordinates of the objects are given in one coordinate system (equinox 2000). The included reading software is rudimentary at best. Thus, even generation of a simple finder chart is not a trivial undertaking. To solve this problem, at least for PC users, GUIDARES was created. GUIDARES is a user-friendly program that lets you look directly at the data in the GSC, either as a graphical sky map or as a text table. GUIDARES can read a sampling of GSC data from a given sky region, store this sampling in a text file, and display a graphical map of the sampled region in projected celestial coordinates (perfect for finder charts). GUIDARES supports rectangular and circular regions defined by coordinates in the equatorial, ecliptic (any equinox) or galactic systems.

Meeting Report from the Genomic Standards Consortium (GSC) Workshop 8

PubMed Central

Kyrpides, Nikos; Field, Dawn; Sterk, Peter; Kottmann, Renzo; Glöckner, Frank Oliver; Hirschman, Lynette; Garrity, George M.; Cochrane, Guy; Wooley, John

2010-01-01

This report summarizes the proceedings of the 8th meeting of the Genomic Standards Consortium held at the Department of Energy Joint Genome Institute in Walnut Creek, CA, USA on September 9-11, 2009. This three-day workshop marked the maturing of Genomic Standards Consortium from an informal gathering of researchers interested in developing standards in the field of genomic and metagenomics to an established community with a defined governance mechanism, its own open access journal, and a family of established standards for describing genomes, metagenomes and marker studies (i.e. ribosomal RNA gene surveys). There will be increased efforts within the GSC to reach out to the wider scientific community via a range of new projects. Further information about the GSC and its activities can be found at http://gensc.org/. PMID:21304696

Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations

PubMed Central

Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

2018-01-01

Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964. PMID:29423027

Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations.

PubMed

Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

2018-01-09

Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964.

Daytime Symptoms in Primary Insomnia: A Prospective Analysis Using Ecological Momentary Assessment

PubMed Central

Buysse, Daniel J.; Thompson, Wesley; Scott, John; Franzen, Peter L.; Germain, Anne; Hall, Martica L.; Moul, Douglas E.; Nofzinger, Eric A.; Kupfer, David J.

2007-01-01

Objectives To prospectively characterize and compare daytime symptoms in primary insomnia (PI) and good sleeper control (GSC) subjects using ecological momentary assessment; to examine relationships between daytime symptom factors, retrospective psychological and sleep reports, and concurrent sleep diary reports. Methods Subjects included 47 PI and 18 GSC. Retrospective self-reports of daytime and sleep symptoms were collected. Daytime symptoms and sleep diary information were then collected for one week on hand-held computers. The Daytime Insomnia Symptom Scale (DISS) consisted of 19 visual analog scales completed four times per day. Factors for the DISS were derived using functional principal components analysis. Nonparametric tests were used to contrast DISS, retrospective symptom ratings, and sleep diary results in PI and GSC subjects, and to examine relationships among them. Results Four principal components were identified for the DISS: Alert Cognition, Negative Mood, Positive Mood, and Sleepiness/Fatigue. PI scored significantly worse than GSC on all four factors (p < .0003 for each). Among PI subjects DISS scales and retrospective psychological symptoms were related to each other in plausible ways. DISS factors were also related to self-report measures of sleep, whereas retrospective psychological symptom measures were not. Conclusions Daytime symptom factors of alertness, positive and negative mood, and sleepiness/fatigue, collected with ecological momentary assessment, showed impairment in PI versus GSC. DISS factors showed stronger relationships to retrospective sleep symptoms and concurrent sleep diary reports than retrospective psychological symptoms. The diurnal pattern of symptoms may inform studies of the pathophysiology and treatment outcome of insomnia. PMID:17368098

p38 MAPK pathway is essential for self-renewal of mouse male germline stem cells (mGSCs).

PubMed

Niu, Zhiwei; Mu, Hailong; Zhu, Haijing; Wu, Jiang; Hua, Jinlian

2017-02-01

Male germline stem cells (mGSCs), also called spermatogonial stem cells (SSCs), constantly generate spermatozoa in male animals. A number of preliminary studies on mechanisms of mGSC self-renewal have previously been conducted, revealing that several factors are involved in this regulated process. The p38 MAPK pathway is widely conserved in multiple cell types in vivo, and plays an important role in cell proliferation, differentiation, inflammation and apoptosis. However, its role in self-renewal of mGSCs has not hitherto been determined. Here, the mouse mGSCs were cultured and their identity was verified by semi-RT-PCR, alkaline phosphatase (AP) staining and immunofluorescence staining. Then, the p38 MAPK pathway was blocked by p38 MAPK-specific inhibitor SB202190. mGSC self-renewal ability was then analysed by observation of morphology, cell number, cell growth analysis, TUNEL incorporation assay and cell cycle analysis. Results showed that mouse mGSC self-renewal ability was significantly inhibited by SB202190. This study showed for the first time that the p38 MAPK pathway plays a key role in maintaining self-renewal capacity of mouse mGSCs, which offers a new self-renewal pathway for these cells and contributes to overall knowledge of the mechanisms of mGSC self-renewal. © 2016 John Wiley & Sons Ltd.

Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

PubMed

Pollak, Julia; Rai, Karan G; Funk, Cory C; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D; Paddison, Patrick J; Ramirez, Jan-Marino; Rostomily, Robert C

2017-01-01

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy

PubMed Central

Pollak, Julia; Rai, Karan G.; Funk, Cory C.; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D.; Paddison, Patrick J.; Ramirez, Jan-Marino; Rostomily, Robert C.

2017-01-01

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance. PMID:28264064

Habitat-Lite: A GSC case study based on free text terms for environmental metadata

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

Kyrpides, Nikos; Hirschman, Lynette; Clark, Cheryl

2008-04-01

There is an urgent need to capture metadata on the rapidly growing number of genomic, metagenomic and related sequences, such as 16S ribosomal genes. This need is a major focus within the Genomic Standards Consortium (GSC), and Habitat is a key metadata descriptor in the proposed 'Minimum Information about a Genome Sequence' (MIGS) specification. The goal of the work described here is to provide a light-weight, easy-to-use (small) set of terms ('Habitat-Lite') that captures high-level information about habitat while preserving a mapping to the recently launched Environment Ontology (EnvO). Our motivation for building Habitat-Lite is to meet the needs ofmore » multiple users, such as annotators curating these data, database providers hosting the data, and biologists and bioinformaticians alike who need to search and employ such data in comparative analyses. Here, we report a case study based on semi-automated identification of terms from GenBank and GOLD. We estimate that the terms in the initial version of Habitat-Lite would provide useful labels for over 60% of the kinds of information found in the GenBank isolation-source field, and around 85% of the terms in the GOLD habitat field. We present a revised version of Habitat-Lite and invite the community's feedback on its further development in order to provide a minimum list of terms to capture high-level habitat information and to provide classification bins needed for future studies.« less

Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells

PubMed Central

Roth, Therese M.; Chiang, C.-Y. Ason; Inaba, Mayu; Yuan, Hebao; Salzmann, Viktoria; Roth, Caitlin E.; Yamashita, Yukiko M.

2012-01-01

Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self-renewal and differentiation. Although asymmetric stem cell division balances between self-renewal and differentiation, it does not dictate how frequently differentiating cells must be produced. In male GSCs, asymmetric GSC division is achieved by stereotyped positioning of the centrosome with respect to the stem cell niche. Recently we showed that the centrosome orientation checkpoint monitors the correct centrosome orientation to ensure an asymmetric outcome of the GSC division. When GSC centrosomes are not correctly oriented with respect to the niche, GSC cell cycle is arrested/delayed until the correct centrosome orientation is reacquired. Here we show that induction of centrosome misorientation upon culture in poor nutrient conditions mediates slowing of GSC cell proliferation via activation of the centrosome orientation checkpoint. Consistently, inactivation of the centrosome orientation checkpoint leads to lack of cell cycle slowdown even under poor nutrient conditions. We propose that centrosome misorientation serves as a mediator that transduces nutrient information into stem cell proliferation, providing a previously unappreciated mechanism of stem cell regulation in response to nutrient conditions. PMID:22357619

MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

PubMed

De Bacco, Francesca; D'Ambrosio, Antonio; Casanova, Elena; Orzan, Francesca; Neggia, Roberta; Albano, Raffaella; Verginelli, Federica; Cominelli, Manuela; Poliani, Pietro L; Luraghi, Paolo; Reato, Gigliola; Pellegatta, Serena; Finocchiaro, Gaetano; Perera, Timothy; Garibaldi, Elisabetta; Gabriele, Pietro; Comoglio, Paolo M; Boccaccio, Carla

2016-05-01

Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy. We elucidate that MET promotes GSC radioresistance through a novel mechanism, relying on AKT activity and leading to (i) sustained activation of Aurora kinase A, ATM kinase, and the downstream effectors of DNA repair, and (ii) phosphorylation and cytoplasmic retention of p21, which is associated with anti-apoptotic functions. We show that MET pharmacological inhibition causes DNA damage accumulation in irradiated GSCs and their depletion in vitro and in GBMs generated by GSC xenotransplantation. Preclinical evidence is thus provided that MET inhibitors can radiosensitize tumors and convert GSC-positive selection, induced by radiotherapy, into GSC eradication. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

New Variable Stars Discovered by Data Mining Images Taken During Recent Asteroid Photometric Observations. Results from the Year 2015

NASA Astrophysics Data System (ADS)

Papini, R.; Franco, L.; Marchini, A.; Salvaggio, F.

2015-12-01

During the past year the authors observed several asteroids for the purpose of determining the rotational period. Typically, this task requires a time series images acquisition on a single field for all the night, weather permitting, for a few nights although not consecutive. Routinely checking this "goldmine," allowed us to discover 14 variable stars not yet listed in catalogs or databases. While the most of the new variables are eclipsing binaries (GSC 01394-01889, GSC 00853-00371, CSS_J171124.7-004042, GSC05065-00218, UCAC4-386-142199, UCAC4 398-127457, UCAC4 384-148138, UCAC4 398-127590, UCAC4-383-155837, GSC-05752-01113, GSC 05765-01271), a few belong to RR Lyrae class (UCAC4 388-136835, 2MASS J20060657-1230376, UCAC4 386-142583). Since asteroid work is definitely time-consuming, follow-up is quite a difficult task for a small group. Further observations of these new variables are therefore strongly encouraged in order to better characterize these stars, especially RR Lyrae ones whose data combined with those taken during professional surveys seem to suggest the presence of a Blazhko effect.

Generalized sidelobe canceler beamforming applied to medical ultrasound imaging

NASA Astrophysics Data System (ADS)

Li, Jiake; Chen, Xiaodong; Wang, Yi; Shi, Yifeng; Yu, Daoyin

2017-03-01

A generalized sidelobe canceler (GSC) approach is proposed for medical ultrasound imaging. The approach uses a set of adaptive weights instead of traditional non-adaptive weights, thus suppressing the interference and noise signal of echo data. In order to verify the validity of the proposed approach, Field II is applied to obtain the echo data of synthetic aperture (SA) for 13 scattering points and circular cysts. The performance of GSC is compared with SA using boxcar weights and Hamming weights, and is quantified by the full width at half maximum (FWHM) and peak signal-to-noise ratio (PSNR). Imaging of scattering point utilizing SA, SA (hamming), GSC provides FWHMs of 1.13411, 1.68910, 0.36195 mm and PSNRs of 60.65, 57.51, 66.72 dB, respectively. The simulation results of circular cyst also show that GSC can perform better lateral resolution than non-adaptive beamformers. Finally, an experiment is conducted on the basis of actual echo data of an ultrasound system, the imaging result after SA, SA (hamming), GSC provides PWHMs of 2.55778, 3.66776, 1.01346 mm at z = 75.6 mm, and 2.65430, 3.76428, 1.27889 mm at z = 77.3 mm, respectively.

Lessons we learned from high-throughput and top-down systems biology analyses about glioma stem cells.

PubMed

Mock, Andreas; Chiblak, Sara; Herold-Mende, Christel

2014-01-01

A growing body of evidence suggests that glioma stem cells (GSCs) account for tumor initiation, therapy resistance, and the subsequent regrowth of gliomas. Thus, continuous efforts have been undertaken to further characterize this subpopulation of less differentiated tumor cells. Although we are able to enrich GSCs, we still lack a comprehensive understanding of GSC phenotypes and behavior. The advent of high-throughput technologies raised hope that incorporation of these newly developed platforms would help to tackle such questions. Since then a couple of comparative genome-, transcriptome- and proteome-wide studies on GSCs have been conducted giving new insights in GSC biology. However, lessons had to be learned in designing high-throughput experiments and some of the resulting conclusions fell short of expectations because they were performed on only a few GSC lines or at one molecular level instead of an integrative poly-omics approach. Despite these shortcomings, our knowledge of GSC biology has markedly expanded due to a number of survival-associated biomarkers as well as glioma-relevant signaling pathways and therapeutic targets being identified. In this article we review recent findings obtained by comparative high-throughput analyses of GSCs. We further summarize fundamental concepts of systems biology as well as its applications for glioma stem cell research.

"A New Arm of the GSC: the RCN4GSC" and "Curation of MIGS-compliant Data" (GSC 8 Meeting)

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

Field, Dawn; Sterk, Peter

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology & Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology & Hydrologymore » follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.« less

A New Arm of the GSC: The RCN4GSC and Curation of MIGS-compliant Data (GSC8 Meeting)

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

Field, Dawn; Sterk, Peter

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology and Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology and Hydrologymore » follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.« less

Meeting Report: “Metagenomics, Metadata and Meta-analysis” (M3) Special Interest Group at ISMB 2009

PubMed Central

Field, Dawn; Friedberg, Iddo; Sterk, Peter; Kottmann, Renzo; Glöckner, Frank Oliver; Hirschman, Lynette; Garrity, George M.; Cochrane, Guy; Wooley, John; Gilbert, Jack

2009-01-01

This report summarizes the proceedings of the “Metagenomics, Metadata and Meta-analysis” (M3) Special Interest Group (SIG) meeting held at the Intelligent Systems for Molecular Biology 2009 conference. The Genomic Standards Consortium (GSC) hosted this meeting to explore the bottlenecks and emerging solutions for obtaining biological insights through large-scale comparative analysis of metagenomic datasets. The M3 SIG included 16 talks, half of which were selected from submitted abstracts, a poster session and a panel discussion involving members of the GSC Board. This report summarizes this one-day SIG, attempts to identify shared themes and recapitulates community recommendations for the future of this field. The GSC will also host an M3 workshop at the Pacific Symposium on Biocomputing (PSB) in January 2010. Further information about the GSC and its range of activities can be found at http://gensc.org/. PMID:21304668

A New Arm of the GSC: The RCN4GSC and Curation of MIGS-compliant Data (GSC8 Meeting)

ScienceCinema

Field, Dawn; Sterk, Peter

2018-01-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology and Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology and Hydrology follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.

Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

PubMed

Andolfi, Laura; Bourkoula, Eugenia; Migliorini, Elisa; Palma, Anita; Pucer, Anja; Skrap, Miran; Scoles, Giacinto; Beltrami, Antonio Paolo; Cesselli, Daniela; Lazzarino, Marco

2014-01-01

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary

PubMed Central

Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting

2014-01-01

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. PMID:24658126

Defining linkages between the GSC and NSF's LTER program: How the Ecological Metadata Language (EML) relates to GCDML and other outcomes

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

Inigo, Gil San; Servilla, Mark; Brunt, James

2008-06-01

The Genomic Standards Consortium (GSC) invited a representative of the Long-Term Ecological Research (LTER) to its fifth workshop to present the Ecological Metadata Language (EML) metadata standard and its relationship to the Minimum Information about a Genome/Metagenome Sequence (MIGS/MIMS) and its implementation, the Genomic Contextual Data Markup Language (GCDML). The LTER is one of the top National Science Foundation (NSF) programs in biology since 1980, representing diverse ecosystems and creating long-term, interdisciplinary research, synthesis of information, and theory. The adoption of EML as the LTER network standard has been key to build network synthesis architectures based on high-quality standardized metadata.more » EML is the NSF-recognized metadata standard for LTER, and EML is a criteria used to review the LTER program progress. At the workshop, a potential crosswalk between the GCDML and EML was explored. Also, collaboration between the LTER and GSC developers was proposed to join efforts toward a common metadata cataloging designer's tool. The community adoption success of a metadata standard depends, among other factors, on the tools and trainings developed to use the standard. LTER's experience in embracing EML may help GSC to achieve similar success. A possible collaboration between LTER and GSC to provide training opportunities for GCDML and the associated tools is being explored. Finally, LTER is investigating EML enhancements to better accommodate genomics data, possibly integrating the GCDML schema into EML. All these action items have been accepted by the LTER contingent, and further collaboration between the GSC and LTER is expected.« less

Defining linkages between the GSC and NSF's LTER program: how the Ecological Metadata Language (EML) relates to GCDML and other outcomes.

PubMed

Gil, Inigo San; Sheldon, Wade; Schmidt, Tom; Servilla, Mark; Aguilar, Raul; Gries, Corinna; Gray, Tanya; Field, Dawn; Cole, James; Pan, Jerry Yun; Palanisamy, Giri; Henshaw, Donald; O'Brien, Margaret; Kinkel, Linda; McMahon, Katherine; Kottmann, Renzo; Amaral-Zettler, Linda; Hobbie, John; Goldstein, Philip; Guralnick, Robert P; Brunt, James; Michener, William K

2008-06-01

The Genomic Standards Consortium (GSC) invited a representative of the Long-Term Ecological Research (LTER) to its fifth workshop to present the Ecological Metadata Language (EML) metadata standard and its relationship to the Minimum Information about a Genome/Metagenome Sequence (MIGS/MIMS) and its implementation, the Genomic Contextual Data Markup Language (GCDML). The LTER is one of the top National Science Foundation (NSF) programs in biology since 1980, representing diverse ecosystems and creating long-term, interdisciplinary research, synthesis of information, and theory. The adoption of EML as the LTER network standard has been key to build network synthesis architectures based on high-quality standardized metadata. EML is the NSF-recognized metadata standard for LTER, and EML is a criteria used to review the LTER program progress. At the workshop, a potential crosswalk between the GCDML and EML was explored. Also, collaboration between the LTER and GSC developers was proposed to join efforts toward a common metadata cataloging designer's tool. The community adoption success of a metadata standard depends, among other factors, on the tools and trainings developed to use the standard. LTER's experience in embracing EML may help GSC to achieve similar success. A possible collaboration between LTER and GSC to provide training opportunities for GCDML and the associated tools is being explored. Finally, LTER is investigating EML enhancements to better accommodate genomics data, possibly integrating the GCDML schema into EML. All these action items have been accepted by the LTER contingent, and further collaboration between the GSC and LTER is expected.

Scaling up stomatal conductance from leaf to canopy using a dual-leaf model for estimating crop evapotranspiration.

PubMed

Ding, Risheng; Kang, Shaozhong; Du, Taisheng; Hao, Xinmei; Zhang, Yanqun

2014-01-01

The dual-source Shuttleworth-Wallace model has been widely used to estimate and partition crop evapotranspiration (λET). Canopy stomatal conductance (Gsc), an essential parameter of the model, is often calculated by scaling up leaf stomatal conductance, considering the canopy as one single leaf in a so-called "big-leaf" model. However, Gsc can be overestimated or underestimated depending on leaf area index level in the big-leaf model, due to a non-linear stomatal response to light. A dual-leaf model, scaling up Gsc from leaf to canopy, was developed in this study. The non-linear stomata-light relationship was incorporated by dividing the canopy into sunlit and shaded fractions and calculating each fraction separately according to absorbed irradiances. The model includes: (1) the absorbed irradiance, determined by separately integrating the sunlit and shaded leaves with consideration of both beam and diffuse radiation; (2) leaf area for the sunlit and shaded fractions; and (3) a leaf conductance model that accounts for the response of stomata to PAR, vapor pressure deficit and available soil water. In contrast to the significant errors of Gsc in the big-leaf model, the predicted Gsc using the dual-leaf model had a high degree of data-model agreement; the slope of the linear regression between daytime predictions and measurements was 1.01 (R2 = 0.98), with RMSE of 0.6120 mm s-1 for four clear-sky days in different growth stages. The estimates of half-hourly λET using the dual-source dual-leaf model (DSDL) agreed well with measurements and the error was within 5% during two growing seasons of maize with differing hydrometeorological and management strategies. Moreover, the estimates of soil evaporation using the DSDL model closely matched actual measurements. Our results indicate that the DSDL model can produce more accurate estimation of Gsc and λET, compared to the big-leaf model, and thus is an effective alternative approach for estimating and partitioning λET.

Scaling Up Stomatal Conductance from Leaf to Canopy Using a Dual-Leaf Model for Estimating Crop Evapotranspiration

PubMed Central

Ding, Risheng; Kang, Shaozhong; Du, Taisheng; Hao, Xinmei; Zhang, Yanqun

2014-01-01

The dual-source Shuttleworth-Wallace model has been widely used to estimate and partition crop evapotranspiration (λET). Canopy stomatal conductance (Gsc), an essential parameter of the model, is often calculated by scaling up leaf stomatal conductance, considering the canopy as one single leaf in a so-called “big-leaf” model. However, Gsc can be overestimated or underestimated depending on leaf area index level in the big-leaf model, due to a non-linear stomatal response to light. A dual-leaf model, scaling up Gsc from leaf to canopy, was developed in this study. The non-linear stomata-light relationship was incorporated by dividing the canopy into sunlit and shaded fractions and calculating each fraction separately according to absorbed irradiances. The model includes: (1) the absorbed irradiance, determined by separately integrating the sunlit and shaded leaves with consideration of both beam and diffuse radiation; (2) leaf area for the sunlit and shaded fractions; and (3) a leaf conductance model that accounts for the response of stomata to PAR, vapor pressure deficit and available soil water. In contrast to the significant errors of Gsc in the big-leaf model, the predicted Gsc using the dual-leaf model had a high degree of data-model agreement; the slope of the linear regression between daytime predictions and measurements was 1.01 (R2 = 0.98), with RMSE of 0.6120 mm s−1 for four clear-sky days in different growth stages. The estimates of half-hourly λET using the dual-source dual-leaf model (DSDL) agreed well with measurements and the error was within 5% during two growing seasons of maize with differing hydrometeorological and management strategies. Moreover, the estimates of soil evaporation using the DSDL model closely matched actual measurements. Our results indicate that the DSDL model can produce more accurate estimation of Gsc and λET, compared to the big-leaf model, and thus is an effective alternative approach for estimating and partitioning λET. PMID:24752329

Discovery and Distribution of Black Smokers on the Western Galapagos Spreading Center: Implications for Spatial and Temporal Controls on High Temperature Venting at Ridge/Hotspot Intersections

NASA Astrophysics Data System (ADS)

Haymon, R. M.; Anderson, P. G.; Baker, E. T.; Resing, J. A.; White, S. M.; MacDonald, K. C.

2006-12-01

Though nearly one-fifth of the mid-ocean ridge (MOR) lies on or near hotspots, it has been debated whether hotspots increase or decrease MOR hydrothermal flux, or affect vent biota. Despite hotspot enhancement of melt supply, high-temperature vent plumes are enigmatically sparse along two previously-surveyed ridge- hotspot intersections [Reykjanes Ridge (RR), Southeast Indian Ridge (SEIR)]. This has been attributed to crustal thickening by excess volcanism. During the 2005-06 GalAPAGoS expedition, we conducted nested sonar, plume, and camera surveys along a 540 km-long portion of the Galapagos Spreading Center (GSC) where the ridge intersects the Galapagos hotspot at lon. 94.5 -89.5 deg. W. Although MOR hydrothermal springs were first found along the eastern GSC crest in 1977 near lon. 86 deg. W, the GalAPAGoS smokers are the first active high-temperature vents to be found anywhere along the Cocos-Nazca plate boundary. Active and/or recently-inactive smokers were located beneath plumes at 5 sites on the seafloor between lon. 91 deg. W and 94.5 deg. W (see Anderson et al., this session) during near-bottom, real-time fiber-optic Medea camera surveys. Smokers occur along eruptive seafloor fissures atop axial volcanic ridges near the middles of ridge segments, mainly in areas underlain by relatively shallow, continuous axial magma chamber (AMC) seismic reflectors. These findings (1) support magmatic, rather than tectonic, control of GSC smoker distribution; (2) demonstrate that thick crust at MOR-hotspot intersections does not prevent high-temperature hydrothermal vents from forming; and, (3) appear to be inconsistent with models suggesting that enhanced hydrothermal cooling causes abrupt deepening of the AMC and transition from non-rifted to rifted GSC morphology near lon. 92.7 deg. W. The widely-spaced smoker sites located on different GSC segments exhibit remarkably similar characteristics and seafloor settings. Most sites are mature or extinct, and are on lava flows of visually-similar ages (estimated to be tens-to-hundreds of years old). Possibly a volcanic pulse may have activated the hotspot- affected western GSC, and powered contemporaneous hydrothermal vents that now are waning. It may be that hotspots produce episodes of near-synchronous, extensive ridge volcanism and hydrothermal activity, followed by periods of quiescence. This idea is consistent with: the episodic eruption histories of Hawaii and Iceland; variably anomalous hydrothermal plume incidence (low on RR, SEIR, GSC; high on Mid-Atlantic Ridge near Azores hotspot); models of episodic melt extraction from mantle plumes; and evidence for magma propagation along hotspot-influenced ridges. Our hypothesis potentially can be tested by studies of gene flow between animal communities located on either side of the Galapagos hotspot, and by dating of GSC hydrothermal chimneys and the lava flows on which they are constructed.

Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche

PubMed Central

Wang, Su; Gao, Yuan; Song, Xiaoqing; Ma, Xing; Zhu, Xiujuan; Mao, Ying; Yang, Zhihao; Ni, Jianquan; Li, Hua; Malanowski, Kathryn E; Anoja, Perera; Park, Jungeun; Haug, Jeff; Xie, Ting

2015-01-01

Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche. DOI: http://dx.doi.org/10.7554/eLife.08174.001 PMID:26452202

Development of germ-line-specific CRISPR-Cas9 systems to improve the production of heritable gene modifications in Arabidopsis

PubMed Central

Mao, Yanfei; Zhang, Zhengjing; Feng, Zhengyan; Wei, Pengliang; Zhang, Hui; Botella, José Ramón; Zhu, Jian-Kang

2017-01-01

Summary The Streptococcus-derived CRISPR/Cas9 system is being widely used to perform targeted gene modifications in plants. This customized endonuclease system has two components, the single-guide RNA (sgRNA) for target DNA recognition and the CRISPR-associated protein 9 (Cas9) for DNA cleavage. Ubiquitously expressed CRISPR/Cas9 systems (UC) generate targeted gene modifications with high efficiency but only those produced in reproductive cells are transmitted to the next generation. We report the design and characterization of a germ-line-specific Cas9 system (GSC) for Arabidopsis gene modification in male gametocytes, constructed using a SPOROCYTELESS (SPL) genomic expression cassette. Four loci in two endogenous genes were targeted by both systems for comparative analysis. Mutations generated by the GSC system were rare in T1 plants but were abundant (30%) in the T2 generation. The vast majority (70%) of the T2 mutant population generated using the UC system were chimeras while the newly developed GSC system produced only 29% chimeras, with 70% of the T2 mutants being heterozygous. Analysis of two loci in the T2 population showed that the abundance of heritable gene mutations was 37% higher in the GSC system compared to the UC system and the level of polymorphism of the mutations was also dramatically increased with the GSC system. Two additional systems based on germ-line-specific promoters (pDD45-GT and pLAT52-GT) were also tested, and one of them was capable of generating heritable homozygous T1 mutant plants. Our results suggest that future application of the described GSC system will facilitate the screening for targeted gene modifications, especially lethal mutations in the T2 population. PMID:26360626

Three-Step Method for Proliferation and Differentiation of Human Embryonic Stem Cell (hESC)-Derived Male Germ Cells

PubMed Central

Lim, Jung Jin; Shim, Myung Sun; Lee, Jeoung Eun; Lee, Dong Ryul

2014-01-01

The low efficiency of differentiation into male germ cell (GC)-like cells and haploid germ cells from human embryonic stem cells (hESCs) reflects the culture method employed in the two-dimensional (2D)-microenvironment. In this study, we applied a three-step media and calcium alginate-based 3D-culture system for enhancing the differentiation of hESCs into male germ stem cell (GSC)-like cells and haploid germ cells. In the first step, embryoid bodies (EBs) were derived from hESCs cultured in EB medium for 3 days and re-cultured for 4 additional days in EB medium with BMP4 and RA to specify GSC-like cells. In the second step, the resultant cells were cultured in GC-proliferation medium for 7 days. The GSC-like cells were then propagated after selection using GFR-α1 and were further cultured in GC-proliferation medium for 3 weeks. In the final step, a 3D-co-culture system using calcium alginate encapsulation and testicular somatic cells was applied to induce differentiation into haploid germ cells, and a culture containing approximately 3% male haploid germ cells was obtained after 2 weeks of culture. These results demonstrated that this culture system could be used to efficiently induce GSC-like cells in an EB population and to promote the differentiation of ESCs into haploid male germ cells. PMID:24690677

Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output

PubMed Central

Sheng, X. Rebecca; Matunis, Erika

2011-01-01

Adult stem cells modulate their output by varying between symmetric and asymmetric divisions, but have rarely been observed in living intact tissues. Germline stem cells (GSCs) in the Drosophila testis are anchored to somatic hub cells and were thought to exclusively undergo oriented asymmetric divisions, producing one stem cell that remains hub-anchored and one daughter cell displaced out of the stem cell-maintaining micro-environment (niche). We developed extended live imaging of the Drosophila testis niche, allowing us to track individual germline cells. Surprisingly, new wild-type GSCs are generated in the niche during steady-state tissue maintenance by a previously undetected event we term `symmetric renewal', where interconnected GSC-daughter cell pairs swivel such that both cells contact the hub. We also captured GSCs undergoing direct differentiation by detaching from the hub. Following starvation-induced GSC loss, GSC numbers are restored by symmetric renewals. Furthermore, upon more severe (genetically induced) GSC loss, both symmetric renewal and de-differentiation (where interconnected spermatogonia fragment into pairs while moving towards then establishing contact with the hub) occur simultaneously to replenish the GSC pool. Thus, stereotypically oriented stem cell divisions are not always correlated with an asymmetric outcome in cell fate, and changes in stem cell output are governed by altered signals in response to tissue requirements. PMID:21752931

RCN4GSC workshop report: managing data at the interface of biodiversity and (meta)genomics, March 2011

USDA-ARS?s Scientific Manuscript database

The Genomic Standards Consortium (GSC) is an international working body with the mission of working towards richer descriptions of genomic and metagenomic data through the development of standards and tools for supporting the consistent documentation of contextual information about sequences. Becaus...

MAXI/GSC detection of a hard-to-soft state transition of MAXI J1727-203, suggesting a black-hole binary

NASA Astrophysics Data System (ADS)

Negoro, H.; Shidatsu, M.; Mihara, T.; Serino, M.; Nakajima, M.; Sakamaki, A.; Maruyama, W.; Nakahira, S.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugizaki, M.; Tachibana, Y.; Morita, K.; Sakamoto, T.; Sugita, S.; Kawakubo, Y.; Hashimoto, T.; Yoshida, A.; Ueno, S.; Tomida, H.; Ishikawa, M.; Isobe, N.; Sugawara, Y.; Shimomukai, R.; Ueda, Y.; Tanimoto, A.; Morita, T.; Yamada, S.; Tsuboi, Y.; Iwakiri, W.; Sasaki, R.; Kawai, H.; Sato, T.; Tsunemi, H.; Yoneyama, T.; Yamauchi, M.; Hidaka, K.; Iwahori, S.; Kawamuro, T.; Yamaoka, K.

2018-06-01

MAXI/GSC observations of the newly discovered X-ray nova MAXI J1727-203 (Yoneyama et al. ATel. #11683, also see ATel #11689, #11690, #11691, #11692) showed energy spectral softening starting from the middle of June 5 (MJD 58274).

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

PubMed

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

MAXI/GSC detection of a hard-to-soft transition of NS-LMXB GS 1826-238

NASA Astrophysics Data System (ADS)

Nakahira, S.; Mihara, T.; Sugizaki, M.; Serino, M.; Morii, M.; Sugimoto, J.; Takagi, T.; Yoshikawa, A.; Matsuoka, M.; Kawai, N.; Yoshii, T.; Tachibana, Y.; Ueno, S.; Tomida, H.; Kimura, M.; Ishikawa, M.; Nakagawa, Y. E.; Negoro, H.; Nakajima, M.; Fukushima, K.; Onodera, T.; Suzuki, K.; Fujita, M.; Namba, T.; Honda, F.; Yoshida, A.; Sakamoto, T.; Kawakubo, Y.; Ohtsuki, H.; Tsunemi, H.; Uchida, D.; Ueda, Y.; Shidatsu, M.; Kawamuro, T.; Hori, T.; Kawagoe, A.; Tsuboi, Y.; Yamauchi, M.; Morooka, Y.; Yamaoka, K.

2014-06-01

We report on a hard-to-soft spectral transition of an X-ray burster GS 1826-238 detected with MAXI/GSC. This source had been consistently observed in the hard state for more than 25 years since the discovery in 1988 (Tanaka 1989, Barret et al. ...

Pettit uses a Grab Sample Container in the FGB during Expedition Six

NASA Image and Video Library

2003-01-22

ISS006-E-20835 (22 January 2003) --- Astronaut Donald R. Pettit, Expedition 6 NASA ISS science officer, holds a Grab Sample Container (GSC) in the functional cargo block (FGB), or Zarya, on the International Space Station (ISS). GSC is used for collecting air samples as part of ISS environmental monitoring.

Active Targets For Capacitive Proximity Sensors

NASA Technical Reports Server (NTRS)

Jenstrom, Del T.; Mcconnell, Robert L.

1994-01-01

Lightweight, low-power active targets devised for use with improved capacitive proximity sensors described in "Capacitive Proximity Sensor Has Longer Range" (GSC-13377), and "Capacitive Proximity Sensors With Additional Driven Shields" (GSC-13475). Active targets are short-distance electrostatic beacons; they generate known alternating electro-static fields used for alignment and/or to measure distances.

Pettit uses a Grab Sample Container in the U.S. Laboratory during Expedition Six

NASA Image and Video Library

2003-01-22

ISS006-E-20834 (22 January 2003) --- Astronaut Donald R. Pettit, Expedition Six NASA ISS science officer, holds a Grab Sample Container (GSC) in the Destiny laboratory on the International Space Station (ISS). GSC is used for collecting air samples as part of ISS environmental monitoring.

Maxi/gsc

NASA Astrophysics Data System (ADS)

Mihara, T.; Maxi Team

2010-12-01

Gas Slit Camera (GSC) is the instrument in the MAXI mission. The GSC utilizes twelve large area proportional counters (PC), a slit and slats collimator. The energy range is 2-30 keV. The GSC has two FOVs of 160 x 3 degrees. One is toward forward direction of ISS and the other is the zenithal direction. Two arches of FOV scans the sky in every 92 minutes with ISS rotation. The slats collimator makes the narrow arc FOV, and the one-dimensional position-resolution of the PC resolves the X-ray sources within the FOV. Thus the position resolution is determined by the slats collimator and a combination of the slit and the position resolution of the detector. These make the point spread function of 1.5 x 1.5 degrees. The background is 1.2 × 10^-4 c/s/cm2 /keV, which is almost the same level with Ginga/LAC. The 5-sigma sensitivity is 15 mCrab/day, which is improved to with the sqrt (t) law. It will reach the 5 sigma confusion limit of 0.5 mCrab in 900 days, if the particle-background estimation is accurate enough.

Generalized sidelobe canceller beamforming method for ultrasound imaging.

PubMed

Wang, Ping; Li, Na; Luo, Han-Wu; Zhu, Yong-Kun; Cui, Shi-Gang

2017-03-01

A modified generalized sidelobe canceller (IGSC) algorithm is proposed to enhance the resolution and robustness against the noise of the traditional generalized sidelobe canceller (GSC) and coherence factor combined method (GSC-CF). In the GSC algorithm, weighting vector is divided into adaptive and non-adaptive parts, while the non-adaptive part does not block all the desired signal. A modified steer vector of the IGSC algorithm is generated by the projection of the non-adaptive vector on the signal space constructed by the covariance matrix of received data. The blocking matrix is generated based on the orthogonal complementary space of the modified steer vector and the weighting vector is updated subsequently. The performance of IGSC was investigated by simulations and experiments. Through simulations, IGSC outperformed GSC-CF in terms of spatial resolution by 0.1 mm regardless there is noise or not, as well as the contrast ratio respect. The proposed IGSC can be further improved by combining with CF. The experimental results also validated the effectiveness of the proposed algorithm with dataset provided by the University of Michigan.

Protective Properties of Radio-Chemoresistant Glioblastoma Stem Cell Clones Are Associated with Metabolic Adaptation to Reduced Glucose Dependence

PubMed Central

Yamada, Kazunari; Tso, Jonathan L.; Menjivar, Jimmy C.; Tian, Jane Y.; Yong, William H.; Schaue, Dörthe; Mischel, Paul S.; Cloughesy, Timothy F.; Nelson, Stanley F.; Liau, Linda M.; McBride, William; Tso, Cho-Lea

2013-01-01

Glioblastoma stem cells (GSC) are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT) with or without temozolomide (TMZ). Only a few single cells survive treatment and regain their self-repopulating capacity. Cells re-populated from treatment-resistant GSC clones contain more clonogenic cells compared to those grown from treatment-sensitive GSC clones, and repeated treatment cycles rapidly enriched clonogenic survival. When compared to sensitive clones, resistant clones exhibited slower tumor development in animals. Upregulated genes identified in resistant clones via comparative expression microarray analysis characterized cells under metabolic stress, including blocked glucose uptake, impaired insulin/Akt signaling, enhanced lipid catabolism and oxidative stress, and suppressed growth and inflammation. Moreover, many upregulated genes highlighted maintenance and repair activities, including detoxifying lipid peroxidation products, activating lysosomal autophagy/ubiquitin-proteasome pathways, and enhancing telomere maintenance and DNA repair, closely resembling the anti-aging effects of caloric/glucose restriction (CR/GR), a nutritional intervention that is known to increase lifespan and stress resistance in model organisms. Although treatment–introduced genetic mutations were detected in resistant clones, all resistant and sensitive clones were subclassified to either proneural (PN) or mesenchymal (MES) glioblastoma subtype based on their expression profiles. Functional assays demonstrated the association of treatment resistance with energy stress, including reduced glucose uptake, fatty acid oxidation (FAO)-dependent ATP maintenance, elevated reactive oxygen species (ROS) production and autophagic activity, and increased AMPK activity and NAD+ levels accompanied by upregulated mRNA levels of SIRT1/PGC-1α axis and DNA repair genes. These data support the view that treatment resistance may arise from quiescent GSC exhibiting a GR-like phenotype, and suggest that targeting stress response pathways of resistant GSC may provide a novel strategy in combination with standard treatment for glioblastoma. PMID:24260384

The connectivity structure, giant strong component and centrality of metabolic networks.

PubMed

Ma, Hong-Wu; Zeng, An-Ping

2003-07-22

Structural and functional analysis of genome-based large-scale metabolic networks is important for understanding the design principles and regulation of the metabolism at a system level. The metabolic network is conventionally considered to be highly integrated and very complex. A rational reduction of the metabolic network to its core structure and a deeper understanding of its functional modules are important. In this work, we show that the metabolites in a metabolic network are far from fully connected. A connectivity structure consisting of four major subsets of metabolites and reactions, i.e. a fully connected sub-network, a substrate subset, a product subset and an isolated subset is found to exist in metabolic networks of 65 fully sequenced organisms. The largest fully connected part of a metabolic network, called 'the giant strong component (GSC)', represents the most complicated part and the core of the network and has the feature of scale-free networks. The average path length of the whole network is primarily determined by that of the GSC. For most of the organisms, GSC normally contains less than one-third of the nodes of the network. This connectivity structure is very similar to the 'bow-tie' structure of World Wide Web. Our results indicate that the bow-tie structure may be common for large-scale directed networks. More importantly, the uncovered structure feature makes a structural and functional analysis of large-scale metabolic network more amenable. As shown in this work, comparing the closeness centrality of the nodes in the GSC can identify the most central metabolites of a metabolic network. To quantitatively characterize the overall connection structure of the GSC we introduced the term 'overall closeness centralization index (OCCI)'. OCCI correlates well with the average path length of the GSC and is a useful parameter for a system-level comparison of metabolic networks of different organisms. http://genome.gbf.de/bioinformatics/

Development of germ-line-specific CRISPR-Cas9 systems to improve the production of heritable gene modifications in Arabidopsis.

PubMed

Mao, Yanfei; Zhang, Zhengjing; Feng, Zhengyan; Wei, Pengliang; Zhang, Hui; Botella, José Ramón; Zhu, Jian-Kang

2016-02-01

The Streptococcus-derived CRISPR/Cas9 system is being widely used to perform targeted gene modifications in plants. This customized endonuclease system has two components, the single-guide RNA (sgRNA) for target DNA recognition and the CRISPR-associated protein 9 (Cas9) for DNA cleavage. Ubiquitously expressed CRISPR/Cas9 systems (UC) generate targeted gene modifications with high efficiency but only those produced in reproductive cells are transmitted to the next generation. We report the design and characterization of a germ-line-specific Cas9 system (GSC) for Arabidopsis gene modification in male gametocytes, constructed using a SPOROCYTELESS (SPL) genomic expression cassette. Four loci in two endogenous genes were targeted by both systems for comparative analysis. Mutations generated by the GSC system were rare in T1 plants but were abundant (30%) in the T2 generation. The vast majority (70%) of the T2 mutant population generated using the UC system were chimeras while the newly developed GSC system produced only 29% chimeras, with 70% of the T2 mutants being heterozygous. Analysis of two loci in the T2 population showed that the abundance of heritable gene mutations was 37% higher in the GSC system compared to the UC system and the level of polymorphism of the mutations was also dramatically increased with the GSC system. Two additional systems based on germ-line-specific promoters (pDD45-GT and pLAT52-GT) were also tested, and one of them was capable of generating heritable homozygous T1 mutant plants. Our results suggest that future application of the described GSC system will facilitate the screening for targeted gene modifications, especially lethal mutations in the T2 population. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Implementing a Model for Evaluation of Teacher Preparation Programs: Results from Two Georgia Institutions.

ERIC Educational Resources Information Center

Adams, John R.; Elmore, Randy F.

Comparisons were made of entering teacher education students' characteristics and attitudes at Georgia Southern College (GSC) and at the University of Georgia (UGA). Major findings were that more students at GSC were female and more were transfers at UGA. Students at UGA possessed higher achievement scores and were more intelligent, assertive, and…

Mixed polyanion glass cathodes: Glass-state conversion reactions

DOE PAGES

Kercher, Andrew K.; Kolopus, James A.; Carroll, Kyler; ...

2015-11-10

Mixed polyanion (MP) glasses can undergo glass-state conversion (GSC) reactions to provide an alternate class of high-capacity cathode materials. GSC reactions have been demonstrated in phosphate/vanadate glasses with Ag, Co, Cu, Fe, and Ni cations. These MP glasses provided high capacity and good high power performance, but suffer from moderate voltages, large voltage hysteresis, and significant capacity fade with cycling. Details of the GSC reaction have been revealed by x-ray absorption spectroscopy, electron microscopy, and energy dispersive x-ray spectroscopy of ex situ cathodes at key states of charge. Using the Open Quantum Materials Database (OQMD), a computational thermodynamic model hasmore » been developed to predict the near-equilibrium voltages of glass-state conversion reactions in MP glasses.« less

Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

PubMed

Laws, Kaitlin M; Sampson, Leesa L; Drummond-Barbosa, Daniela

2015-03-15

Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate. Copyright © 2015 Elsevier Inc. All rights reserved.

Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.

PubMed

Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Fortner, Karen A; Viapiano, Mariano S; Jaworski, Diane M

2015-08-01

Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth. © 2015 Wiley Periodicals, Inc.

Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest

PubMed Central

Long, Patrick M.; Tighe, Scott W.; Driscoll, Heather E.; Fortner, Karen A.; Viapiano, Mariano S.; Jaworski, Diane M.

2015-01-01

Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-L-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth. PMID:25573156

Effects of alfalfa silage storage structure and roasting corn on ruminal digestion and microbial CP synthesis in lactating dairy cows

USDA-ARS?s Scientific Manuscript database

The objective of this experiment was to determine the effects of unroasted ground shelled corn (GSC) or roasted GSC (RGSC), when fed with alfalfa, ensiled in bag, bunker, or O2-limiting tower silos on ruminal digestion and microbial protein synthesis in lactating dairy cows. The roasted corn was hea...

MAXI/GSC detection of a new outburst from the black hole candidate H 1743-322

NASA Astrophysics Data System (ADS)

Shidatsu, M.; Nakahira, S.; Negoro, H.; Ueno, S.; Tomida, H.; Ishikawa, M.; Sugawara, Y.; Nakagawa, Y. E.; Mihara, T.; Sugizaki, M.; Serino, M.; Iwakiri, W.; Sugimoto, J.; Takagi, T.; Matsuoka, M.; Kawai, N.; Isobe, N.; Sugita, S.; Yoshii, T.; Tachibana, Y.; Ono, Y.; Fujiwara, T.; Harita, S.; Muraki, Y.; Yoshida, A.; Sakamoto, T.; Kawakubo, Y.; Kitaoka, Y.; Tsunemi, H.; Shomura, R.; Nakajima, M.; Tanaka, K.; Masumitsu, T.; Kawase, T.; Ueda, Y.; Kawamuro, T.; Hori, T.; Tanimoto, A.; Oda, S.; Tsuboi, Y.; Nakamura, Y.; Sasaki, R.; Yamauchi, M.; Furuya, K.; Yamaoka, K.

2016-11-01

The MAXI/GSC nova-alert system detected an X-ray brightening of the Galactic black hole candidate H 1743-322 in November 6, UT 03:01. The 2-20 keV flux increased from 12 +- 3 mCrab on November 4 (MJD 57696) to 37 +- 5 mCrab on November 6 (MJD 57698).

Toxicological Assessment of ISS Air Quality: SpaceX-2 First Ingress

NASA Technical Reports Server (NTRS)

Meyers, Valerie

2013-01-01

One mini-grab sample container (M-GSC) was collected by crew members onboard ISS during first ingress into SpaceX-2 on March 3, 2013, three days after late cargo loading and a pre-launch clean air purge. Recoveries of the three surrogate standards from the m-GSC were: 13C-acetone, 97%; fluorobenzene, 95%; and chlorobenzene, 68%.

MIENS Minimum Information about an ENvironmental Sequence and The GSC's Not-for-Profit (GSC8 Meeting)

ScienceCinema

Yilmaz, Pelin; Kolker, Eugene

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Pelin Yilmaz of the Max Planck Institute-Bremen talks about the MIENS specification and Eugene Kolker of Seattle Children's Hospital discusses the GSC's non-for-profit at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts.

PubMed

Wildburger, Norelle C; Wood, Paul L; Gumin, Joy; Lichti, Cheryl F; Emmett, Mark R; Lang, Frederick F; Nilsson, Carol L

2015-06-05

Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studies have demonstrated the feasibility of harnessing the homing capacity of BM-hMSCs for targeted delivery of cancer therapeutics, it is now also evident, based on clinically relevant glioma stem cell (GSC) models of GBMs, that BM-hMSCs demonstrate variable tropism toward these tumors. In this study, we compared the lipid environment of GSC xenografts that attract BM-hMSCs (N = 9) with those that do not attract (N = 9) to identify lipid modalities that are conducive to homing of BM-hMSC to GBMs. We identified lipids directly from tissue by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) of lipid extracts. Several species of signaling lipids, including phosphatidic acid (PA 36:2, PA 40:5, PA 42:5, and PA 42:7) and diacylglycerol (DAG 34:0, DAG 34:1, DAG 36:1, DAG 38:4, DAG 38:6, and DAG 40:6), were lower in attracting xenografts. Molecular lipid images showed that PA (36:2), DAG (40:6), and docosahexaenoic acid (DHA) were decreased within tumor regions of attracting xenografts. Our results provide the first evidence for lipid signaling pathways and lipid-mediated tumor inflammatory responses in the homing of BM-hMSCs to GSC xenografts. Our studies provide new fundamental knowledge on the molecular correlates of the differential homing capacity of BM-hMSCs toward GSC xenografts.

Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

NASA Astrophysics Data System (ADS)

Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

2016-02-01

Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation.

Dexamethasone-mediated oncogenicity in vitro and in an animal model of glioblastoma.

PubMed

Luedi, Markus M; Singh, Sanjay K; Mosley, Jennifer C; Hassan, Islam S A; Hatami, Masumeh; Gumin, Joy; Andereggen, Lukas; Sulman, Erik P; Lang, Frederick F; Stueber, Frank; Fuller, Gregory N; Colen, Rivka R; Zinn, Pascal O

2018-01-12

OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort. METHODS Expression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520). RESULTS The mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature. CONCLUSIONS The authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients' prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

Defining Linkages between the GSC and NSF's LTER Program: How the Ecological Metadata Language (EML) Relates to GCDML and Other Outcomes

Treesearch

Inigo San Gil; Wade Sheldon; Tom Schmidt; Mark Servilla; Raul Aguilar; Corinna Gries; Tanya Gray; Dawn Field; James Cole; Jerry Yun Pan; Giri Palanisamy; Donald Henshaw; Margaret O' Brien; Linda Kinkel; Kathrine McMahon; Renzo Kottmann; Linda Amaral-Zettler; John Hobbie; Philip Goldstein; Robert P. Guralnick; James Brunt; William K. Michener

2008-01-01

The Genomic Standards Consortium (GSC) invited a representative of the Long-Term Ecological Research (LTER) to its fifth workshop to present the Ecological Metadata Language (EML) metadata standard and its relationship to the Minimum Information about a Genome/Metagenome Sequence (MIGS/MIMS) and its implementation, the Genomic Contextual Data Markup Language (GCDML)....

Flash Updates of GSC projects (GSC8 Meeting)

ScienceCinema

Glockner, Frank Oliver; Markowitz, Victor; Kyrpides, Nikos; Meyer, Folker; Amaral-Zettler, Linda; Cole, James

2018-01-25

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. In quick succession Frank Oliver Glockner (MPI-Bremen), Victor Markowitz (LBNL), Nikos Kyripides (JGI), Folker Meyer (ANL), Linda Amaral-Zettler (Marine Biology Lab), and James Cole (Michigan State University) provide updates on a number of topics related to GSC projects at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Flash Updates of GSC projects (GSC8 Meeting)

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

Glockner, Frank Oliver; Markowitz, Victor; Kyrpides, Nikos

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. In quick succession Frank Oliver Glockner (MPI-Bremen), Victor Markowitz (LBNL), Nikos Kyripides (JGI), Folker Meyer (ANL), Linda Amaral-Zettler (Marine Biology Lab), and James Colemore » (Michigan State University) provide updates on a number of topics related to GSC projects at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients.

PubMed

Afshar-Oromieh, Ali; Holland-Letz, Tim; Giesel, Frederik L; Kratochwil, Clemens; Mier, Walter; Haufe, Sabine; Debus, Nils; Eder, Matthias; Eisenhut, Michael; Schäfer, Martin; Neels, Oliver; Hohenfellner, Markus; Kopka, Klaus; Kauczor, Hans-Ulrich; Debus, Jürgen; Haberkorn, Uwe

2017-08-01

Since the clinical introduction of 68 Ga-PSMA-11 PET/CT, this imaging method has rapidly spread and is now regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to analyse the influence of several variables with possible influence on PSMA ligand uptake in a large cohort. We performed a retrospective analysis of 1007 consecutive patients who were scanned with 68 Ga-PSMA-11 PET/CT (1 h after injection) from January 2014 to January 2017 to detect recurrent disease. Patients with untreated primary PCa or patients referred for PSMA radioligand therapy were excluded. The possible effects of different variables including PSA level and PSA doubling time (PSA DT ), PSA velocity (PSA Vel ), Gleason score (GSC, including separate analysis of GSC 7a and 7b), ongoing androgen deprivation therapy (ADT), patient age and amount of injected activity were evaluated. In 79.5% of patients at least one lesion with characteristics suggestive of recurrent PCa was detected. A pathological (positive) PET/CT scan was associated with PSA level and ADT. GSC, amount of injected activity, patient age, PSA DT and PSA Vel were not associated with a positive PET/CT scan in multivariate analysis. 68 Ga-PSMA-11 PET/CT detects tumour lesions in a high percentage of patients with recurrent PCa. Tumour detection is clearly associated with PSA level and ADT. Only a tendency for an association without statistical significance was found between higher GSC and a higher probability of a pathological PET/CT scan. No associations were found between a pathological 68 Ga-PSMA-11 PET/CT scan and patient age, amount of injected activity, PSA DT or PSA Vel.

First hydrothermal active vent discovered on the Galapagos Microplate

NASA Astrophysics Data System (ADS)

Tao, C.; Li, H.; Wu, G.; Su, X.; Zhang, G.; Chinese DY115-21 Leg 3 Scientific Party

2011-12-01

The Galapagos Microplate (GM) lies on the western Gaplapagos Spreading Center (GSC), representing one of the classic Ridge-Ridge-Ridge (R-R-R) plate boundaries of the Nazca, Cocos, and Pacific plates. The presence of the 'black smoke' and hydrothermal vent community were firstly confirmed on the GSC. Lots of hydrothermal fields were discovered on the center and eastern GSC, while the western GSC has not been well investigated. During 17th Oct. to 9th Nov. 2009, the 3rd leg of Chinese DY115-21 cruise with R/V Dayangyihao has been launched along 2°N-5°S near equatorial East Pacific Rise (EPR). Two new hydrothermal fields were confirmed. One is named 'Precious Stone Mountain', which is the first hydrothermal field on the GM. The other is found at 101.47°W, 0.84°S EPR. The 'Precious Stone Mountain' hydrothermal field (at 101.49°W, 1.22°N) is located at an off-axial seamount on the southern GM boundary, with a depth from 1,450 to 1,700m. Hydrothermal fluids emitting from the fissures and hydrothermal fauna were captured by deep-tow video. Few mineral clasts of pyrite and chalcopyrite were separated from one sediment sample, but no sulfide chimney was found yet. Hydrothermal fauna such as alive mussels, crabs, shrimps, tubeworms, giant clams, as well as rock samples were collected by TV-Grab. The study of the seafloor classification with Simrad EM120 multi-beam echosounder has been conducted on the 'Precious Stone Mountain' hydrothermal field. The result indicates that seafloor materials around the hydrothermal field can be characterized into three types, such as the fresh lava, hydrothermal sediment, and altered rock.

Expression analysis of some genes regulated by retinoic acid in controls and triadimefon-exposed embryos: is the amphibian Xenopus laevis a suitable model for gene-based comparative teratology?

PubMed

Di Renzo, Francesca; Rossi, Federica; Bacchetta, Renato; Prati, Mariangela; Giavini, Erminio; Menegola, Elena

2011-06-01

The use of nonmammal models in teratological studies is a matter of debate and seems to be justified if the embryotoxic mechanism involves conserved processes. Published data on mammals and Xenopus laevis suggest that azoles are teratogenic by altering the endogenous concentration of retinoic acid (RA). The expression of some genes (Shh, Ptch-1, Gsc, and Msx2) controlled by retinoic acid is downregulated in rat embryos exposed at the phylotypic stage to the triazole triadimefon (FON). In order to propose X. laevis as a model for gene-based comparative teratology, this work evaluates the expression of Shh, Ptch-1, Gsc, and Msx2 in FON-exposed X. laevis embryos. Embryos, exposed to a high concentration level (500 µM) of FON from stage 13 till 17, were examined at stages 17, 27, and 47. Stage 17 and 27 embryos were processed to perform quantitative RT-PCR. The developmental rate was never affected by FON at any considered stage. FON-exposed stage 47 larvae showed the typical craniofacial malformations. A significant downregulation of Gsc was observed in FON-exposed stage 17 embryos. Shh, Ptch-1, Msx2 showed a high fluctuation of expression both in control and in FON-exposed samples both at stages 17 and 27. The downregulation of Gsc mimics the effects of FON on rat embryos, showing for this gene a common effect of FON in the two vertebrate classes. The high fluctuation observed in the gene expression of the other genes, however, suggests that X. laevis at this stage has limited utility for gene-based comparative teratology. © 2011 Wiley-Liss, Inc.

Mantle plume capture, anchoring, and outflow during Galápagos plume-ridge interaction

NASA Astrophysics Data System (ADS)

Gibson, S. A.; Geist, D. J.; Richards, M. A.

2015-05-01

Compositions of basalts erupted between the main zone of Galápagos plume upwelling and adjacent Galápagos Spreading Center (GSC) provide important constraints on dynamic processes involved in transfer of deep-mantle-sourced material to mid-ocean ridges. We examine recent basalts from central and northeast Galápagos including some that have less radiogenic Sr, Nd, and Pb isotopic compositions than plume-influenced basalts (E-MORB) from the nearby ridge. We show that the location of E-MORB, greatest crustal thickness, and elevated topography on the GSC correlates with a confined zone of low-velocity, high-temperature mantle connecting the plume stem and ridge at depths of ˜100 km. At this site on the ridge, plume-driven upwelling involving deep melting of partially dehydrated, recycled ancient oceanic crust, plus plate-limited shallow melting of anhydrous peridotite, generate E-MORB and larger amounts of melt than elsewhere on the GSC. The first-order control on plume stem to ridge flow is rheological rather than gravitational, and strongly influenced by flow regimes initiated when the plume was on axis (>5 Ma). During subsequent northeast ridge migration material upwelling in the plume stem appears to have remained "anchored" to a contact point on the GSC. This deep, confined NE plume stem-to-ridge flow occurs via a network of melt channels, embedded within the normal spreading and advection of plume material beneath the Nazca plate, and coincides with locations of historic volcanism. Our observations require a more dynamically complex model than proposed by most studies, which rely on radial solid-state outflow of heterogeneous plume material to the ridge.

Pediatric Glioblastoma Therapies Based on Patient-Derived Stem Cell Resources

DTIC Science & Technology

2014-11-01

genomic DNA and then subjected to Illumina high-throughput sequencing . In this analysis, shRNAs lost in the GSC population represent candidate gene...and genomic DNA and then subjected to Illumina high-throughput sequencing . In this analysis, shRNAs lost in the GSC population represent candidate...PRISM 7900 Sequence Detection System ( Genomics Resource, FHCRC). Relative transcript abundance was analyzed using the 2−ΔΔCt method. TRIzol (Invitrogen

Synthesis of Biodiesel in Batch and Packed-Bed Reactors Using Powdered and Granular Sugar Catalyst

NASA Astrophysics Data System (ADS)

Janaun, J.; Lim, P. M.; Balan, W. S.; Yaser, A. Z.; Chong, K. P.

2017-06-01

Increasing world production of palm oil warrants effective utilization of its waste. In particular, conversion of waste cooking oil into biodiesel has obtained global interest because of renewable energy need and reduction of CO2 emission. In this study, oleic acid used as a model compound for waste cooking oil conversion using esterification reaction catalysed by sugar catalyst (SC) in powdered (P-SC) and granular (G-SC) forms. The catalysts were synthesized via incomplete carbonization of D-glucose followed by functionalization with concentrated sulphuric acid. Catalysts characterizations were done for their physical and chemical properties using modern tools. Batch and packed-bed reactor systems were used to evaluate the reactivity of the catalysts. The results showed that G-SC had slightly higher total acidity and more porous than P-SC. The experimental conditions for batch reaction were temperature of 60°C, molar ratio of 1:20 (Oleic Acid:Methanol) and 2 wt. catalyst with respect to oleic acid. The results showed the maximum oleic acid conversion using G-SC and P-SC were 52 and 48, respectively. Whereas, the continuous reaction with varying feed flow rate as a function of retention time was studied by using 3 g of P-SC in 60 °C and 1:20 molar ratio in a packed-bed reactor. The results showed that a longer retention time which was 6.48 min and feed flow rate 1.38 ml/min, achieved higher average conversion of 9.9 and decreased with further increasing flow rate. G-SC showed a better average conversion of 10.8 at lowest feed flow rate of 1.38 ml/min in continuous reaction experiments. In a broader perspective, large scale continuous biodiesel production is feasible using granular over powdered catalyst mainly due to it lower pressure drop.

Detection of the thermal component in GRB 160107A

NASA Astrophysics Data System (ADS)

Kawakubo, Yuta; Sakamoto, Takanori; Nakahira, Satoshi; Yamaoka, Kazutaka; Serino, Motoko; saoka, Yoichi; Cherry, Michael L.; Matsukawa, Shohei; Mori, Masaki; Nakagawa, Yujin; Ozawa, Shunsuke; Penacchioni, Ana V.; Ricciarini, Sergio B.; Tezuka, Akira; Torii, Shoji; Yamada, Yusuke; Yoshida, Atsumasa

2018-01-01

We present the detection of a blackbody component in gamma-ray burst GRB 160107A emission by using the combined spectral data of the CALET Gamma-ray Burst Monitor (CGBM) and the MAXI Gas Slit Camera (GSC). MAXI/GSC detected the emission ˜45 s prior to the main burst episode observed by the CGBM. The MAXI/GSC and the CGBM spectrum of this prior emission period is fitted well by a blackbody with temperature 1.0^{+0.3}_{-0.2} keV plus a power law with a photon index of -1.6 ± 0.3. We discuss the radius of the photospheric emission and the main burst emission based on the observational properties. We stress the importance of coordinated observations via various instruments collecting high-quality data over a broad energy coverage in order to understand the GRB prompt emission mechanism.

The actin-binding protein profilin is required for germline stem cell maintenance and germ cell enclosure by somatic cyst cells

PubMed Central

Shields, Alicia R.; Spence, Allyson C.; Yamashita, Yukiko M.; Davies, Erin L.; Fuller, Margaret T.

2014-01-01

Specialized microenvironments, or niches, provide signaling cues that regulate stem cell behavior. In the Drosophila testis, the JAK-STAT signaling pathway regulates germline stem cell (GSC) attachment to the apical hub and somatic cyst stem cell (CySC) identity. Here, we demonstrate that chickadee, the Drosophila gene that encodes profilin, is required cell autonomously to maintain GSCs, possibly facilitating localization or maintenance of E-cadherin to the GSC-hub cell interface. Germline specific overexpression of Adenomatous Polyposis Coli 2 (APC2) rescued GSC loss in chic hypomorphs, suggesting an additive role of APC2 and F-actin in maintaining the adherens junctions that anchor GSCs to the niche. In addition, loss of chic function in the soma resulted in failure of somatic cyst cells to maintain germ cell enclosure and overproliferation of transit-amplifying spermatogonia. PMID:24346697

Minimum information about a marker gene sequence (MIMARKS) and minimum information about any (x) sequence (MIxS) specifications

PubMed Central

Yilmaz, Pelin; Kottmann, Renzo; Field, Dawn; Knight, Rob; Cole, James R; Amaral-Zettler, Linda; Gilbert, Jack A; Karsch-Mizrachi, Ilene; Johnston, Anjanette; Cochrane, Guy; Vaughan, Robert; Hunter, Christopher; Park, Joonhong; Morrison, Norman; Rocca-Serra, Philippe; Sterk, Peter; Arumugam, Manimozhiyan; Bailey, Mark; Baumgartner, Laura; Birren, Bruce W; Blaser, Martin J; Bonazzi, Vivien; Booth, Tim; Bork, Peer; Bushman, Frederic D; Buttigieg, Pier Luigi; Chain, Patrick S G; Charlson, Emily; Costello, Elizabeth K; Huot-Creasy, Heather; Dawyndt, Peter; DeSantis, Todd; Fierer, Noah; Fuhrman, Jed A; Gallery, Rachel E; Gevers, Dirk; Gibbs, Richard A; Gil, Inigo San; Gonzalez, Antonio; Gordon, Jeffrey I; Guralnick, Robert; Hankeln, Wolfgang; Highlander, Sarah; Hugenholtz, Philip; Jansson, Janet; Kau, Andrew L; Kelley, Scott T; Kennedy, Jerry; Knights, Dan; Koren, Omry; Kuczynski, Justin; Kyrpides, Nikos; Larsen, Robert; Lauber, Christian L; Legg, Teresa; Ley, Ruth E; Lozupone, Catherine A; Ludwig, Wolfgang; Lyons, Donna; Maguire, Eamonn; Methé, Barbara A; Meyer, Folker; Muegge, Brian; Nakielny, Sara; Nelson, Karen E; Nemergut, Diana; Neufeld, Josh D; Newbold, Lindsay K; Oliver, Anna E; Pace, Norman R; Palanisamy, Giriprakash; Peplies, Jörg; Petrosino, Joseph; Proctor, Lita; Pruesse, Elmar; Quast, Christian; Raes, Jeroen; Ratnasingham, Sujeevan; Ravel, Jacques; Relman, David A; Assunta-Sansone, Susanna; Schloss, Patrick D; Schriml, Lynn; Sinha, Rohini; Smith, Michelle I; Sodergren, Erica; Spor, Aymé; Stombaugh, Jesse; Tiedje, James M; Ward, Doyle V; Weinstock, George M; Wendel, Doug; White, Owen; Whiteley, Andrew; Wilke, Andreas; Wortman, Jennifer R; Yatsunenko, Tanya; Glöckner, Frank Oliver

2012-01-01

Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences—the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The ‘environmental packages’ apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere. PMID:21552244

Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis.

PubMed

Cui, Qi; Yang, Su; Ye, Peng; Tian, E; Sun, Guoqiang; Zhou, Jiehua; Sun, Guihua; Liu, Xiaoxuan; Chen, Chao; Murai, Kiyohito; Zhao, Chunnian; Azizian, Krist T; Yang, Lu; Warden, Charles; Wu, Xiwei; D'Apuzzo, Massimo; Brown, Christine; Badie, Behnam; Peng, Ling; Riggs, Arthur D; Rossi, John J; Shi, Yanhong

2016-02-03

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

Characterization of immortalized dairy goat male germline stem cells (mGSCs).

PubMed

Zhu, Haijing; Ma, Jing; Du, Rui; Zheng, Liming; Wu, Jiang; Song, Wencong; Niu, Zhiwei; He, Xin; Du, Enqi; Zhao, Shanting; Hua, Jinlian

2014-09-01

Male germline stem cells (mGSCs), in charge for the fertility in male testis, are the only kind of adult stem cells that transmit genetic information to next generation, with promising prospects in germplasm resources preservation and optimization, and production of transgenic animals. Mouse male germline stem cell lines have been established and are valuable for studying the mechanisms of spermatogenesis. However, there is a lack of stable mGSC cell lines in livestock, which restricts the progress of transgenic research and related biotechnology. Here, we firstly established an immortalized dairy goat mGSC cell line to study the biological properties and the signaling pathways associated with mGSCs self-renewal and differentiation. The ectopic factors SV40 large T antigen and Bmi1 genes were transduced into dairy goat mGSCs, and the results showed that the proliferation of these cells that were named mGSCs-I-SB was improved significantly. They maintained the typical characteristics including the expression of mGSC markers, and the potential to differentiate into all three germ layers, sperm-like cells in vitro. Additionally, mGSCs-I-SB survived and differentiated into three germ layer cell types when they were transplanted into chicken embryos. Importantly, the cells also survived in mouse spermatogenesis deficiency model testis which seemed to be the golden standard to examine mGSCs. Conclusively, our results demonstrate that mGSCs-I-SB present the characteristics of mGSCs and may promote the future study on goat mGSCs. © 2014 Wiley Periodicals, Inc.

STS 131 Return Samples: Assessment of Air Quality Aboard the Shuttle (STS-131) and International Space Station (19A)

NASA Technical Reports Server (NTRS)

James, John T.

2010-01-01

The toxicological assessments of 1 grab sample canister (GSC) from the Shuttle are reported in Table 1. Analytical methods have not changed from earlier reports. The recoveries of the 3 surrogates (C-13-acetone, fluorobenzene, and chlorobenzene) from the Shuttle GSC were 100%, 93%, and 101%, respectively. Based on the historical experience using end-of-mission samples, the Shuttle atmosphere was acceptable for human respiration.

Clinical and Physiological Correlates of Caffeine and Caffeine Metabolites in Primary Insomnia

PubMed Central

Youngberg, Mark R.; Karpov, Irina O.; Begley, Amy; Pollock, Bruce G.; Buysse, Daniel J.

2011-01-01

Objectives: To explore the relationship between plasma concentrations of caffeine and subjective and polysomnographic measures of sleep in both good sleeper controls (GSC) and individuals with primary insomnia (PI), following the consumption of low-moderate quantities of caffeine in the home environment. Methods: 65 PI and 29 GSC, each consuming < 4 four coffee cup equivalents of caffeine daily, were recruited. Subjects completed a diary detailing sleep habits and caffeine consumption, one night of polysomnography, and a blood sample for measurement of plasma caffeine and its metabolites at bedtime. Plasma concentrations of caffeine, its primary metabolite, paraxanthine, and other metabolites were determined for each subject and correlated with self-report and polysomnographic measures. Results: No statistically significant differences were found between GSC and PI with respect to number of caffeinated beverages consumed (p = 0.91), estimated absolute caffeine ingestion (p = 0.48), time of caffeine consumption (p = 0.22), or plasma concentrations of caffeine (p = 0.92) or paraxanthine (p = 0.88). Significant correlations were found between plasma concentrations of caffeine/paraxanthine and endorsed caffeine intake (r = 0.58, p < 0.05) and estimated absolute caffeine ingestion (r = 0.57, p < 0.05). Plasma caffeine/paraxanthine was significantly correlated with percent stage 1 sleep (r = 0.32, p < 0.05). However, plasma concentrations of caffeine/paraxanthine were not significantly correlated with other subjective or polysomnographic measures of sleep disturbance in either GSC or PI. Conclusions: These data suggest that low-moderate amounts of caffeine consumed in the home environment, and mostly during morning hours, have little effect on subjective or polysomnographic measures of sleep in GSC or PI. Citation: Youngberg MR; Karpov IO; Begley A; Pollock BG; Buysse DJ. Clinical and physiological correlates of caffeine and caffeine metabolites in primary insomnia. J Clin Sleep Med 2011;7(2):196-203. PMID:21509336

Swift/BAT and MAXI/GSC monitoring indicate a new outburst of black hole transient H 1743-322

NASA Astrophysics Data System (ADS)

Zhang, Hui; Yu, Wenfei; Lin, Jie; Zhang, Wenda; Yan, Zhen

2015-06-01

Swift/BAT and MAXI/GSC monitoring in the X-rays show that the black hole binary transient H 1743-322 has started a new outburst. The Swift/BAT X-ray intensity increased from 0.007+/-0.003 counts/s/cm^2 (0.029+/-0.012 Crab) on MJD 57177 to 0.024+/-0.002 counts/s/cm^2 (0.105+/-0.007 Crab) on MJD 57181 in 15-50 keV.

Soyuz 7 Return Samples: Assessment of Air Quality Aboard the International Space Station

NASA Technical Reports Server (NTRS)

James, John T.

2004-01-01

The toxicological assessments of one grab sample canister (GSC), 6 dual sorbent tubes (DSTs), and 20 formaldehyde badges returned aboard Soyuz 7 are reported. Analytical methods have not changed from earlier reports. Surrogate standard recoveries from the GSC were 84-89%. The recoveries of the less volatile surrogates from the DSTs were 87 to 112%; however, 13C-acetone was only recovered at 53-59%. Formaldehyde recoveries from 2 lab controls were 87 and 95%; trip controls were not returned to ground.

Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro.

PubMed

Tezcan, Gulcin; Taskapilioglu, Mevlut Ozgur; Tunca, Berrin; Bekar, Ahmet; Demirci, Hilal; Kocaeli, Hasan; Aksoy, Secil Ak; Egeli, Unal; Cecener, Gulsah; Tolunay, Sahsine

2017-06-01

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis

PubMed Central

Cui, Qi; Yang, Su; Ye, Peng; Tian, E.; Sun, Guoqiang; Zhou, Jiehua; Sun, Guihua; Liu, Xiaoxuan; Chen, Chao; Murai, Kiyohito; Zhao, Chunnian; Azizian, Krist T.; Yang, Lu; Warden, Charles; Wu, Xiwei; D'Apuzzo, Massimo; Brown, Christine; Badie, Behnam; Peng, Ling; Riggs, Arthur D.; Rossi, John J.; Shi, Yanhong

2016-01-01

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma. PMID:26838672

Mapping lava morphology of the Galapagos Spreading Center at 92°W: fuzzy logic provides a classification of high-resolution bathymetry and backscatter

NASA Astrophysics Data System (ADS)

McClinton, J. T.; White, S. M.; Sinton, J. M.; Rubin, K. H.; Bowles, J. A.

2010-12-01

Differences in axial lava morphology along the Galapagos Spreading Center (GSC) can indicate variations in magma supply and emplacement dynamics due to the influence of the adjacent Galapagos hot spot. Unfortunately, the ability to discriminate fine-scale lava morphology has historically been limited to observations of the small coverage areas of towed camera surveys and submersible operations. This research presents a neuro-fuzzy approach to automated seafloor classification using spatially coincident, high-resolution bathymetry and backscatter data. The classification method implements a Sugeno-type fuzzy inference system trained by a multi-layered adaptive neural network and is capable of rapidly classifying seafloor morphology based on attributes of surface geometry and texture. The system has been applied to the 92°W segment of the western GSC in order to quantify coverage areas and distributions of pillow, lobate, and sheet lava morphology. An accuracy assessment has been performed on the classification results. The resulting classified maps provide a high-resolution view of GSC axial morphology and indicate the study area terrain is approximately 40% pillow flows, 40% lobate and sheet flows, and 10% fissured or faulted area, with about 10% of the study area unclassifiable. Fine-scale features such as eruptive fissures, tumuli, and individual pillowed lava flow fronts are also visible. Although this system has been applied to lava morphology, its design and implementation are applicable to other undersea mapping applications.

DET/MPS - The GSFC Energy Balance Programs

NASA Technical Reports Server (NTRS)

Jagielski, J. M.

1994-01-01

Direct Energy Transfer (DET) and MultiMission Spacecraft Modular Power System (MPS) computer programs perform mathematical modeling and simulation to aid in design and analysis of DET and MPS spacecraft power system performance in order to determine energy balance of subsystem. DET spacecraft power system feeds output of solar photovoltaic array and nickel cadmium batteries directly to spacecraft bus. MPS system, Standard Power Regulator Unit (SPRU) utilized to operate array at array's peak power point. DET and MPS perform minute-by-minute simulation of performance of power system. Results of simulation focus mainly on output of solar array and characteristics of batteries. Both packages limited in terms of orbital mechanics, they have sufficient capability to calculate data on eclipses and performance of arrays for circular or near-circular orbits. DET and MPS written in FORTRAN-77 with some VAX FORTRAN-type extensions. Both available in three versions: GSC-13374, for DEC VAX-series computers running VMS. GSC-13443, for UNIX-based computers. GSC-13444, for Apple Macintosh computers.

A control strategy for grid-side converter of DFIG under unbalanced condition based on Dig SILENT/Power Factory

NASA Astrophysics Data System (ADS)

Han, Pingping; Zhang, Haitian; Chen, Lingqi; Zhang, Xiaoan

2018-01-01

The models of doubly fed induction generator (DFIG) and its grid-side converter (GSC) are established under unbalanced grid condition based on DIgSILENT/PowerFactory. According to the mathematical model, the vector equations of positive and negative sequence voltage and current are deduced in the positive sequence synchronous rotating reference frame d-q-0 when the characteristics of the simulation software are considered adequately. Moreover, the reference value of current component of GSC in the positive sequence frame d-q-0 under unbalanced condition can be obtained to improve the traditional control of GSC when the national issue of unbalanced current limits is combined. The simulated results indicate that the control strategy can restrain negative sequence current and the two times frequency power wave of GSC’s ac side effectively. The voltage of DC bus can be maintained a constant to ensure the uninterrupted operation of DFIG under unbalanced grid condition eventually.

Superfund Record of Decision (EPA Region 2): Garden State Cleaners, Buena Borough, Atlantic County, NJ. (First remedial action), September 1991. Final report

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

Not Available

1991-09-26

The 3,000-square-foot Garden State Cleaners (GSC) site is an active dry cleaning operation in Minotola, Bueno Borough, Atlantic County, New Jersey. Land use in the area is residential and commercial, and local residents obtain drinking water from the Borough municipal water supply system. From 1966 to the present, dry cleaning activities using PCE were conducted at the GSC site, and until 1985, wastes were discharged through pipes directly into the ground. In 1984, State investigations showed elevated levels of PCE in ground water adjacent to and downgradient from the GSC and SJCC facilities, and elevated levels of PCE and TCEmore » in onsite soil. The selected remedial action for the site includes treating onsite approximately 1,600 cubic yards of contaminated soil using in-situ vapor extraction; treating the contaminated wastewater from the vapor extraction processes onsite using an air stripping column; treating air emissions using carbon adsorption units; pumping and onsite treatment of contaminated ground water using air stripping and carbon adsorption; reinjecting the treated ground water upgradient from the site; regenerating spent activated carbon from both treatment processes offsite; conducting long-term ground water monitoring; and implementing temporary institutional controls. The estimated present worth cost for the remedial action at the GSC site is $5,451,000, which includes an estimated annual O and M cost of $249,500 for 70 years.« less

MAXI/GSC detection of a new outburst from SAX J1810.8-2609

NASA Astrophysics Data System (ADS)

Negoro, H.; Mihara, T.; Nakahira, S.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugizaki, M.; Tachibana, Y.; Morita, K.; Sakamoto, T.; Serino, M.; Sugita, S.; Kawakubo, Y.; Hashimoto, T.; Yoshida, A.; Nakajima, M.; Sakamaki, A.; Maruyama, W.; Ueno, S.; Tomida, H.; Ishikawa, M.; Sugawara, Y.; Isobe, N.; Shimomukai, R.; Ueda, Y.; Tanimoto, A.; Morita, T.; Yamada, S.; Tsuboi, Y.; Iwakiri, W.; Sasaki, R.; Kawai, H.; Sato, T.; Tsunemi, H.; Yoneyama, T.; Yamauchi, M.; Hidaka, K.; Iwahori, S.; Kawamuro, T.; Yamaoka, K.; Shidatsu, M.

2018-05-01

We report a new X-ray outburst from the low-mass X-ray binary SAX J1810.8-2609 (aka V4722 Sgr; Ubertini et al. 1998, IAUC 6838) observed with MAXI/GSC. The enhancement was recognized from 2018 April 23 (MJD 58231), and X-ray count rates in the 2-4 keV and 4-10 keV bands peaked on April 26 at 0.085 +/- 0.008 c/s/cm2 ( 80 mCrab) and 0.096+/-0.008 c/s/cm2 ( 82 mCrab), respectively.

Stellar occultation candidates from the guide star catalog. I - Saturn, 1991-1999

NASA Technical Reports Server (NTRS)

Bosh, A. S.; Mcdonald, S. W.

1992-01-01

A list of 203 potential occultations by Saturn and its ring of stars from the HST Guide Star Catalog (GSC) during the years 1991-1999 is presented. This list features many fainter candidates than do current occultation candidate lists for Saturn; these fainter stars can also provide a high signal-to-noise ratio if observed with a large telescope or in the IR where Saturn and its rings have absorption bands. The occultation circumstances are listed, as well as star information found in the GSC.

Human Factors and Safety Evaluation of the Special Communications System AN/GSC-40 Combined Ground Command Post Terminal

DTIC Science & Technology

1984-12-01

and physical dimensions of pieces of equipment in those cases where adverse comments had been made by operators and maintainers. The questionnaire...the urgent requirement to deploy the AN/MSC-64 FT’s, a decision was made to procure an Interim Command Post (ICP). A contract was awarded 1 Oct 80...12.0 F E-5 33 5.6 304X6 15.5 7 . . . (3) Four times the temperature and humidity were measured with a hand-held psychrometer B4477. The effective

Lectures on Non-Abelian Bosonization

NASA Astrophysics Data System (ADS)

Tsvelik, A. M.

The following sections are included: * Introduction * Kac-Moody algebra * Conformal embedding. Sugawara Hamiltonian * SU(N)×SU(M) model * From the fermionic to WZNW model * The perturbed SUk(2) WZNW model * Correlation functions and Quasi Long Range order * Generalization from SU(2) to SU(N) * A model with Sp(2N) symmetry * Solution for the special case gcdw = gsc * Attraction in the orbital channel. Competing orders. Emergent integrability. ZN parafermions. * Parafermion zero modes * Conclusions and Acknowledgements * Appendix A. TBA equations for the Sp1(2N) model * Appendix B. Bosonization of of Z4 parafermions * References

Pharmacological inhibition of poly(ADP-ribose) polymerase-1 modulates resistance of human glioblastoma stem cells to temozolomide

PubMed Central

2014-01-01

Background Chemoresistance of glioblastoma multiforme (GBM) has been attributed to the presence within the tumor of cancer stem cells (GSCs). The standard therapy for GBM consists of surgery followed by radiotherapy and the chemotherapeutic agent temozolomide (TMZ). However, TMZ efficacy is limited by O6-methylguanine-DNA-methyltransferase (MGMT) and Mismatch Repair (MMR) functions. Strategies to counteract TMZ resistance include its combination with poly(ADP-ribose) polymerase inhibitors (PARPi), which hamper the repair of N-methylpurines. PARPi are also investigated as monotherapy for tumors with deficiency of homologous recombination (HR). We have investigated whether PARPi may restore GSC sensitivity to TMZ or may be effective as monotherapy. Methods Ten human GSC lines were assayed for MMR proteins, MGMT and PARP-1 expression/activity, MGMT promoter methylation and sensitivity to TMZ or PARPi, alone and in combination. Since PTEN defects are frequently detected in GBM and may cause HR dysfunction, PTEN expression was also analyzed. The statistical analysis of the differences in drug sensitivity among the cell lines was performed using the ANOVA and Bonferroni’s post-test or the non-parametric Kruskal-Wallis analysis and Dunn’s post-test for multiple comparisons. Synergism between TMZ and PARPi was analyzed by the median-effect method of Chou and Talalay. Correlation analyses were done using the Spearman’s rank test. Results All GSCs were MMR-proficient and resistance to TMZ was mainly associated with high MGMT activity or low proliferation rate. MGMT promoter hypermethylation of GSCs correlated both with low MGMT activity/expression (Spearman’s test, P = 0.004 and P = 0.01) and with longer overall survival of GBM patients (P = 0.02). Sensitivity of each GSC line to PARPi as single agent did not correlate with PARP-1 or PTEN expression. Notably, PARPi and TMZ combination exerted synergistic antitumor effects in eight out of ten GSC lines and the TMZ dose reduction achieved significantly correlated with the sensitivity of each cell line to PARPi as single agent (P = 0.01). Conclusions The combination of TMZ with PARPi may represent a valuable strategy to reverse GSC chemoresistance. PMID:24593254

Transient tidal eddy motion in the western Gulf of Maine, part 1: Primary structure

NASA Astrophysics Data System (ADS)

Brown, W. S.; Marques, G. M.

2013-07-01

High frequency radar-derived surface current maps of the Great South Channel (GSC) in the western Gulf of Maine in 2005 revealed clockwise (CW) and anticlockwise (ACW) eddy motion associated with the strong regional tidal currents. To better elucidate the kinematics and dynamics of these transient tidal eddy motions, an observational and modeling study was conducted during the weakly stratified conditions of winter 2008-2009. Our moored bottom pressure and ADCP current measurements in 13m depth were augmented by historical current measurements in about 30m in documenting the dominance of highly polarized M2 semidiurnal currents in our nearshore study region. The high-resolution finite element coastal ocean model (QUODDY) - forced by the five principal tidal constituents - produced maps depicting the formation and evolution of the CW and ACW eddy motions that regularly follow maximum ebb and flood flows, respectively. Observation versus model current comparison required that the model bottom current drag coefficient be set to at an unusually high Cd=0.01 - suggesting the importance of form drag in the study region. The observations and model results were consistent in diagnosing CW or ACW eddy motions that (a) form nearshore in the coastal boundary layer (CBL) for about 3h after the respective tidal current maxima and then (b) translate southeastward across the GSC along curved 50m isobath at speeds of about 25m/s. Observation-based and model-based momentum budget estimates were consistent in showing a first order forced semidiurnal standing tidal wave dynamics (like the adjacent Gulf of Maine) which was modulated by adverse pressure gradient/bottom stress forcing to generate the eddy motions. Observation-based estimates of terms in the transport vorticity budget showed that in the shallower Inner Zone subregion (average depth=23m) that the diffusion of nearshore vorticity was dominant in feeding the growth of eddy motion vorticity; while in the somewhat deeper Outer Zone subregion (33m) bottom current lateral shear and water column stretching/squashing was significant in modulating the eddy motion. We conclude that the transient eddy motions in the GSC region are phase eddies that accompany the change of tide across the GSC and are (1) generated by bottom stress gradients in the shallower nearshore - an issue which needs to be better understood for improved future forecasting.

Stellar spectral classification of previously unclassified stars GSC 4461-698 and GSC 4466-870

NASA Astrophysics Data System (ADS)

Grau, Darren Moser

Stellar spectral classification is one of the first efforts undertaken to begin defining the physical characteristics of stars. However, many stars lack even this basic information, which is the foundation for later research to constrain stellar effective temperatures, masses, radial velocities, the number of stars in the system, and age. This research obtained visible-λ stellar spectra via the testing and commissioning of a Santa Barbara Instruments Group (SBIG) Self-Guiding Spectrograph (SGS) at the UND Observatory. Utilizing a 16-inch-aperture telescope on Internet Observatory #3, the SGS obtained spectra of GSC 4461-698 and GSC 4466-870 in the low-resolution mode using an 18-µm wide slit with dispersion of 4.3 Å/pixel, resolution of 8 Å, and a spectral range from 3800-7500 Å. Observational protocols include automatic bias/dark frame subtraction for each stellar spectrum obtained. This was followed by spectral averaging to obtain a combined spectrum for each star observed. Image calibration and spectral averaging was performed using the software programs, Maxim DL, Image J, Microsoft Excel, and Winmk. A wavelength calibration process was used to obtain spectra of an Hg/Ne source that allowed the conversion of spectrograph channels into wavelengths. Stellar emission and absorption lines, such as those for hydrogen (H) and helium (He), were identified, extracted, and rectified. Each average spectrum was compared to the MK stellar spectral standards to determine an initial spectral classification for each star. The hope is that successful completion of this project will allow long-term stellar spectral observations to begin at the UND Observatory.

Transforming GSC-II Magnitudes into JWST/FGS Count Rates

NASA Astrophysics Data System (ADS)

Holfeltz, Sherie T.; Chayer, P.; Nelan, E. P.

2010-01-01

The JWST Fine Guidance Sensor (FGS) will provide the positions of guide stars to the spacecraft attitude control system to facilitate the fine pointing of the Observatory. The FGS is an infrared camera operating in an unfiltered passband from 0.6 to 5.3 microns. The ground system will select guide stars from the Guide Star Catalog II (GSC-II), which is an all-sky catalog with three optical passbands (BJ, RF, IN) derived from photographic plates, and from 2MASS. We present a method for predicting a guide star's FGS photon count rate, which is needed to operate the FGS. The method consists of first deriving equations for transforming the GSC-II optical passbands into J, H, and K for stars that are below the 2MASS faint limiting magnitude, based upon fitting the distribution of brighter stars in color-color diagrams using GSC-II and 2MASS photometry. Next, we convolve the BJ, RF, IN and predicted J, H, and K magnitudes (or 2MASS magnitudes if available) for a given star with the wavelength dependent throughput and sensitivity of the telescope and FGS. To estimate the accuracy of this method for stars that are too faint for 2MASS, we compare the predicted J, H, and K magnitudes for a large sample of stars to data from the United Kingdom Infrared Telescope (UKIRT) Deep Sky Survey (UKIDSS) Large Area Survey (LAS). Using synthetic magnitudes computed from Kurucz models for stars of different spectral types, we show that the method should provide reliable FGS count rates.

Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

PubMed

Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

2005-01-01

The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and inhibit differentiation of glioma stem-like cells.

PubMed

Long, Patrick M; Moffett, John R; Namboodiri, Aryan M A; Viapiano, Mariano S; Lawler, Sean E; Jaworski, Diane M

2013-09-06

Metabolic reprogramming is a pathological feature of cancer and a driver of tumor cell transformation. N-Acetylaspartate (NAA) is one of the most abundant amino acid derivatives in the brain and serves as a source of metabolic acetate for oligodendrocyte myelination and protein/histone acetylation or a precursor for the synthesis of the neurotransmitter N-acetylaspartylglutamate (NAAG). NAA and NAAG as well as aspartoacylase (ASPA), the enzyme responsible for NAA degradation, are significantly reduced in glioma tumors, suggesting a possible role for decreased acetate metabolism in tumorigenesis. This study sought to examine the effects of NAA and NAAG on primary tumor-derived glioma stem-like cells (GSCs) from oligodendroglioma as well as proneural and mesenchymal glioblastoma, relative to oligodendrocyte progenitor cells (Oli-Neu). Although the NAA dicarboxylate transporter NaDC3 is primarily thought to be expressed by astrocytes, all cell lines expressed NaDC3 and, thus, are capable of NAA up-take. Treatment with NAA or NAAG significantly increased GSC growth and suppressed differentiation of Oli-Neu cells and proneural GSCs. Interestingly, ASPA was expressed in both the cytosol and nuclei of GSCs and exhibited greatest nuclear immunoreactivity in differentiation-resistant GSCs. Both NAA and NAAG elicited the expression of a novel immunoreactive ASPA species in select GSC nuclei, suggesting differential ASPA regulation in response to these metabolites. Therefore, this study highlights a potential role for nuclear ASPA expression in GSC malignancy and suggests that the use of NAA or NAAG is not an appropriate therapeutic approach to increase acetate bioavailability in glioma. Thus, an alternative acetate source is required.

Research on green supply chain coordination strategy for uncertain market demand.

PubMed

Cao, Jian; Chen, Yangyang; Lu, Bo; Tong, Chenlu; Zhou, Gengui

2015-03-01

Based on the status that the green market began to develop (e.g. pharmaceutical industry) in Mainland China, the paper mainly discusses how members of the green supply chain (GSC) cooperate effectively in the process of the supply chain operations. For the uncertainties existing in the market demand of the green products, the GSC coordination strategy is put forward based on the Stackelberg game that the manufacturer is the leader and distributors are the followers. The relationship between the proposed coordination strategy and several factors including the distributor's amount, the distributor's risk aversion and the uncertainties of market demand are analyzed. It indicates that, when there are uncertainties existing in the market demand of the green product, the revenue of each enterprise, the overall revenue and the customer's welfare all decrease; while the increase in the number of distributors and low risk aversion of them are beneficial to the entire GSC and the customer. The conclusions have good guidance for the operational decisions of the green supply chain when the green market is in its initial formation.

Enhanced Photocarrier Separation in Hierarchical Graphitic-C3N4-Supported CuInS2 for Noble-Metal-Free Z-Scheme Photocatalytic Water Splitting.

PubMed

Li, Xiaoxue; Xie, Keyu; Song, Long; Zhao, Mengjia; Zhang, Zhipan

2017-07-26

The effective separation of photogenerated electrons and holes in photocatalysts is a prerequisite for efficient photocatalytic water splitting. CuInS 2 (CIS) is a widely used light absorber that works properly in photovoltaics but only shows limited performance in solar-driven hydrogen evolution due to its intrinsically severe charge recombination. Here, we prepare hierarchical graphitic C 3 N 4 -supported CuInS 2 (denoted as GsC) by an in situ growth of CIS directly on exfoliated thin graphitic C 3 N 4 nanosheets (g-C 3 N 4 NS) and demonstrate efficient separation of photoinduced charge carriers in the GsC by forming the Z-scheme system for the first time in CIS-catalyzed water splitting. Under visible light illumination, the GsC features an enhanced hydrogen evolution rate up to 1290 μmol g -1 h -1 , which is 3.3 and 6.1 times higher than that of g-C 3 N 4 NS and bare-CIS, respectively, thus setting a new performance benchmark for CIS-based water-splitting photocatalysts.

MAXI/GSC discovery of a new X-ray transient MAXI J1727-203

NASA Astrophysics Data System (ADS)

Yoneyama, T.; Negoro, H.; Nakajima, M.; Sakamaki, A.; Maruyama, W.; Mihara, T.; Nakahira, S.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugizaki, M.; Tachibana, Y.; Morita, K.; Sakamoto, T.; Serino, M.; Sugita, S.; Kawakubo, Y.; Hashimoto, T.; Yoshida, A.; Ueno, S.; Tomida, H.; Ishikawa, M.; Isobe, N.; Sugawara, Y.; Shimomukai, R.; Ueda, Y.; Tanimoto, A.; Morita, T.; Yamada, S.; Tsuboi, Y.; Iwakiri, W.; Sasaki, R.; Kawai, H.; Sato, T.; Tsunemi, H.; Yamauchi, M.; Hidaka, K.; Iwahori, S.; Kawamuro, T.; Yamaoka, K.; Shidatsu, M.

2018-06-01

The MAXI/GSC nova alert system (Negoro et al. 2016, PASJ, 68, S1) triggered on an uncatalogued X-ray transient source at 09:41 UT on 2018 June 05. Assuming that the source flux was constant over three scan transits from 9:41 to 12:46, we obtain the source position at (R.A., Dec) = (261.971 deg, -20.389 deg) = (17 27 53, -20 23 20) (J2000) with a statistical 90% C.L. elliptical error region with long and short radii of 0.33 deg and 0.28 deg, respectively.

Improved Photometric Characteristics of the Newly Discovered EW-Type System GSC 04370-00206

NASA Astrophysics Data System (ADS)

Breus, V. V.; Andronov, I. L.; Dubovsky, P. A.; Hegedus, T.; Kudzej, I.; Petrik, K.

2010-12-01

We present results of two-color photometric study of the newly discovered EW-type eclipsing binary star GSC 04370-00206 in the field of the intermediate polar MU Cam. CCD V,R observations were obtained in the Astronomical Observatories in Hlohovec, Baja and Kolonica in 2007-2009. Improved photometric elements for the primary minimum were determined: Min.BJD=2454805.75635+0.44264511(27)E. The range of the brightness variations is 13.79-14.13 (V) and 13.07-13.44 (R). The accuracy of the period determination is by a factor of ˜ 7, 000 times better than the one published by the discoverers based on only one night of observations. We report on the night-to-night variability of the shape of the light curve which is interpreted by a presence of spots in the atmosphere of one or both components (O'Connel effect).

Properties of samples containing natural gas hydrate from the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well, determined using Gas Hydrate And Sediment Test Laboratory Instrument (GHASTLI)

USGS Publications Warehouse

Winters, W.J.

1999-01-01

As part of an ongoing laboratory study, preliminary acoustic, strength, and hydraulic conductivity results are presented from a suite of tests conducted on four natural-gas-hydrate-containing samples from the Mackenzie Delta JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well. The gas hydrate samples were preserved in pressure vessels during transport from the Northwest Territories to Woods Hole, Massachusetts, where multistep tests were performed using GHASTLI (Gas Hydrate And Sediment Test Laboratory Instrument), which recreates pressure and temperature conditions that are stable for gas hydrate. Properties and changes in sediment behaviour were measured before, during, and after controlled gas hydrate dissociation. Significant amounts of gas hydrate occupied the sample pores and substantially increased acoustic velocity and shear strength.

Molecular markers in glioma.

PubMed

Ludwig, Kirsten; Kornblum, Harley I

2017-09-01

Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians

PubMed Central

Saberi, Amir; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A.

2016-01-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development. PMID:27163480

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

PubMed

Saberi, Amir; Jamal, Ayana; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A

2016-05-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development.

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma

PubMed Central

Singer, E; Judkins, J; Salomonis, N; Matlaf, L; Soteropoulos, P; McAllister, S; Soroceanu, L

2015-01-01

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN–MES transition. This ‘reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM. PMID:25590811

Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann–Mangold organizer

PubMed Central

Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

2012-01-01

How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann–Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer. PMID:22492356

Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.

PubMed

Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

2012-05-01

How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann-Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer.

N-Acetylaspartate (NAA) and N-Acetylaspartylglutamate (NAAG) Promote Growth and Inhibit Differentiation of Glioma Stem-like Cells*

PubMed Central

Long, Patrick M.; Moffett, John R.; Namboodiri, Aryan M. A.; Viapiano, Mariano S.; Lawler, Sean E.; Jaworski, Diane M.

2013-01-01

Metabolic reprogramming is a pathological feature of cancer and a driver of tumor cell transformation. N-Acetylaspartate (NAA) is one of the most abundant amino acid derivatives in the brain and serves as a source of metabolic acetate for oligodendrocyte myelination and protein/histone acetylation or a precursor for the synthesis of the neurotransmitter N-acetylaspartylglutamate (NAAG). NAA and NAAG as well as aspartoacylase (ASPA), the enzyme responsible for NAA degradation, are significantly reduced in glioma tumors, suggesting a possible role for decreased acetate metabolism in tumorigenesis. This study sought to examine the effects of NAA and NAAG on primary tumor-derived glioma stem-like cells (GSCs) from oligodendroglioma as well as proneural and mesenchymal glioblastoma, relative to oligodendrocyte progenitor cells (Oli-Neu). Although the NAA dicarboxylate transporter NaDC3 is primarily thought to be expressed by astrocytes, all cell lines expressed NaDC3 and, thus, are capable of NAA up-take. Treatment with NAA or NAAG significantly increased GSC growth and suppressed differentiation of Oli-Neu cells and proneural GSCs. Interestingly, ASPA was expressed in both the cytosol and nuclei of GSCs and exhibited greatest nuclear immunoreactivity in differentiation-resistant GSCs. Both NAA and NAAG elicited the expression of a novel immunoreactive ASPA species in select GSC nuclei, suggesting differential ASPA regulation in response to these metabolites. Therefore, this study highlights a potential role for nuclear ASPA expression in GSC malignancy and suggests that the use of NAA or NAAG is not an appropriate therapeutic approach to increase acetate bioavailability in glioma. Thus, an alternative acetate source is required. PMID:23884408

Assessing the short-term clock drift of early broadband stations with burst events of the 26 s persistent and localized microseism

NASA Astrophysics Data System (ADS)

Xie, Jun; Ni, Sidao; Chu, Risheng; Xia, Yingjie

2018-01-01

Accurate seismometer clock plays an important role in seismological studies including earthquake location and tomography. However, some seismic stations may have clock drift larger than 1 s (e.g. GSC in 1992), especially in early days of global seismic networks. The 26 s Persistent Localized (PL) microseism event in the Gulf of Guinea sometime excites strong and coherent signals, and can be used as repeating source for assessing stability of seismometer clocks. Taking station GSC, PAS and PFO in the TERRAscope network as an example, the 26 s PL signal can be easily observed in the ambient noise cross-correlation function between these stations and a remote station OBN with interstation distance about 9700 km. The travel-time variation of this 26 s signal in the ambient noise cross-correlation function is used to infer clock error. A drastic clock error is detected during June 1992 for station GSC, but not found for station PAS and PFO. This short-term clock error is confirmed by both teleseismic and local earthquake records with a magnitude of 25 s. Averaged over the three stations, the accuracy of the ambient noise cross-correlation function method with the 26 s source is about 0.3-0.5 s. Using this PL source, the clock can be validated for historical records of sparsely distributed stations, where the usual ambient noise cross-correlation function of short-period (<20 s) ambient noise might be less effective due to its attenuation over long interstation distances. However, this method suffers from cycling problem, and should be verified by teleseismic/local P waves. Further studies are also needed to investigate whether the 26 s source moves spatially and its effects on clock drift detection.

Robust decentralized power system controller design: Integrated approach

NASA Astrophysics Data System (ADS)

Veselý, Vojtech

2017-09-01

A unique approach to the design of gain scheduled controller (GSC) is presented. The proposed design procedure is based on the Bellman-Lyapunov equation, guaranteed cost and robust stability conditions using the parameter dependent quadratic stability approach. The obtained feasible design procedures for robust GSC design are in the form of BMI with guaranteed convex stability conditions. The obtained design results and their properties are illustrated in the simultaneously design of controllers for simple model (6-order) turbogenerator. The results of the obtained design procedure are a PI automatic voltage regulator (AVR) for synchronous generator, a PI governor controller and a power system stabilizer for excitation system.

Observations of candidate oscillating eclipsing binaries and two newly discovered pulsating variables

NASA Astrophysics Data System (ADS)

Liakos, A.; Niarchos, P.

2009-03-01

CCD observations of 24 eclipsing binary systems with spectral types ranging between A0-F0, candidate for containing pulsating components, were obtained. Appropriate exposure times in one or more photometric filters were used so that short-periodic pulsations could be detected. Their light curves were analyzed using the Period04 software in order to search for pulsational behaviour. Two new variable stars, namely GSC 2673-1583 and GSC 3641-0359, were discov- ered as by-product during the observations of eclipsing variables. The Fourier analysis of the observations of each star, the dominant pulsation frequencies and the derived frequency spectra are also presented.

Spline-Screw Payload-Fastening System

NASA Technical Reports Server (NTRS)

Vranish, John M.

1994-01-01

Payload handed off securely between robot and vehicle or structure. Spline-screw payload-fastening system includes mating female and male connector mechanisms. Clockwise (or counter-clockwise) rotation of splined male driver on robotic end effector causes connection between robot and payload to tighten (or loosen) and simultaneously causes connection between payload and structure to loosen (or tighten). Includes mechanisms like those described in "Tool-Changing Mechanism for Robot" (GSC-13435) and "Self-Aligning Mechanical and Electrical Coupling" (GSC-13430). Designed for use in outer space, also useful on Earth in applications needed for secure handling and secure mounting of equipment modules during storage, transport, and/or operation. Particularly useful in machine or robotic applications.

An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma.

PubMed

Gujar, Amit D; Le, Son; Mao, Diane D; Dadey, David Y A; Turski, Alice; Sasaki, Yo; Aum, Diane; Luo, Jingqin; Dahiya, Sonika; Yuan, Liya; Rich, Keith M; Milbrandt, Jeffrey; Hallahan, Dennis E; Yano, Hiroko; Tran, David D; Kim, Albert H

2016-12-20

Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD + ). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD + synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD + levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD + -dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD + metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.

Collateral damage control in cancer therapy: defining the stem identity in gliomas.

PubMed

Hsieh, David

2011-01-01

The discovery of discrete functional components in cancer systems advocates a paradigm shift in therapeutic design towards the targeted destruction of critical cellular constituents that fuel tumorigenic potential. In astrocytomas, malignant growth can be propagated and sustained by glioma stem cells (GSCs) endowed with highly efficient clonogenic and tumor initiation capacities. Given their disproportionate oncogenic contribution, GSCs are often considered the optimal targets for curative treatment because their eradication may subvert the refractory nature of GBMs. However, the close affinity of GSCs and normal neural stem cells (NSCs) is a cautionary note for off-target effects of GSC-based therapies. In fact, many parallels can be drawn between GSC and NSC functions, which ostensibly rely on a communal collection of stem cell-promoting transcription factors (TFs). Only through rigorous scrutiny of nuances in the stemness program of GSCs and NSCs may we clarify the pathogenic mechanisms of stemness factors and reveal processes exploited by cancer cells to co-opt stem cell traits. Importantly, discerning the specific requirements for GSC and NSC maintenance may be an essential requisite when assessing molecular targets for discriminatory targeting of GSCs with minimal sequelae.

Method for validating cloud mask obtained from satellite measurements using ground-based sky camera.

PubMed

Letu, Husi; Nagao, Takashi M; Nakajima, Takashi Y; Matsumae, Yoshiaki

2014-11-01

Error propagation in Earth's atmospheric, oceanic, and land surface parameters of the satellite products caused by misclassification of the cloud mask is a critical issue for improving the accuracy of satellite products. Thus, characterizing the accuracy of the cloud mask is important for investigating the influence of the cloud mask on satellite products. In this study, we proposed a method for validating multiwavelength satellite data derived cloud masks using ground-based sky camera (GSC) data. First, a cloud cover algorithm for GSC data has been developed using sky index and bright index. Then, Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data derived cloud masks by two cloud-screening algorithms (i.e., MOD35 and CLAUDIA) were validated using the GSC cloud mask. The results indicate that MOD35 is likely to classify ambiguous pixels as "cloudy," whereas CLAUDIA is likely to classify them as "clear." Furthermore, the influence of error propagations caused by misclassification of the MOD35 and CLAUDIA cloud masks on MODIS derived reflectance, brightness temperature, and normalized difference vegetation index (NDVI) in clear and cloudy pixels was investigated using sky camera data. It shows that the influence of the error propagation by the MOD35 cloud mask on the MODIS derived monthly mean reflectance, brightness temperature, and NDVI for clear pixels is significantly smaller than for the CLAUDIA cloud mask; the influence of the error propagation by the CLAUDIA cloud mask on MODIS derived monthly mean cloud products for cloudy pixels is significantly smaller than that by the MOD35 cloud mask.

Chemical composition and some anti-nutrient content of raw and processed bitter vetch (Vicia ervilia) seed for use as feeding stuff in poultry diet.

PubMed

Sadeghi, Gh; Pourreza, J; Samei, A; Rahmani, H

2009-01-01

An experiment was conducted to determine chemical composition of raw and treated bitter vetch seed for use in poultry diets. Processing methods were: soaked in water for 12 h, then autoclaved and dried (SA); coarsely ground, soaked in water for 24 h, autoclaved and dried (GSA); coarsely ground, soaked in water for 47 h with exchange of water every 12 h, cooked and dried (GSC); coarsely ground, soaked in solution of 1% acetic acid for 24 h at 60 degrees C and dried (GAA). Raw bitter vetch seed was contained 94.52, 26.56, 0.4, 58.86, 3.38, 5.32, 12.28 and 14.20 percent DM, CP, EE, NFE, Ash, CF, ADF and NDF, respectively. Its GE, AME, AMEn, TME and TMEn values were 18.10, 13.15, 14.38, 14.10 and 14.69 MJ/kg, respectively. Results indicated that bitter vetch is a good source of Fe (340 ppm) and Cu (46.7 ppm). It s amino acid profile was suitable and methionine was the first limiting amino acid when compared with broiler and layer chicks requirements. Its canavanine and tannin content were 0.78 and 6.7 mg/kgDM, respectively. Processing methods improved CP and in some cases AMEn. All processing methods especially GSC resulted in a significant (P < 0.05) reduction in canavanine and tannin.

Module Cluster: UG - 001.00 (GSC) Urban Geography.

ERIC Educational Resources Information Center

Currier, Wade R.

This is one of several module clusters developed for the Camden Teacher Corps project. This module cluster is designed to introduce students to urban studies through the application of a geographic approach. Although geography shares with other social sciences many concepts and methods, it has contributed a distinctive set of viewpoints and a…

The Drosophila nuclear lamina protein otefin is required for germline stem cell survival.

PubMed

Barton, Lacy J; Pinto, Belinda S; Wallrath, Lori L; Geyer, Pamela K

2013-06-24

LEM domain (LEM-D) proteins are components of an extensive protein network that assembles beneath the inner nuclear envelope. Defects in LEM-D proteins cause tissue-restricted human diseases associated with altered stem cell homeostasis. Otefin (Ote) is a Drosophila LEM-D protein that is intrinsically required for female germline stem cell (GSC) maintenance. Previous studies linked Ote loss with transcriptional activation of the key differentiation gene bag-of-marbles (bam), leading to the model in which Ote tethers the bam gene to the nuclear periphery for gene silencing. Using genetic and phenotypic analyses of multiple ote(-/-) backgrounds, we obtained evidence that is inconsistent with this model. We show that bam repression is maintained in ote(-/-) GSCs and that germ cell loss persists in ote(-/-), bam(-/-) mutants, together demonstrating that GSC loss is independent of bam transcription. We show that the primary defect in ote(-/-) GSCs is a block of differentiation, which ultimately leads to germ cell death. Copyright © 2013 Elsevier Inc. All rights reserved.

Day-night cycles and the sleep-promoting factor, Sleepless, affect stem cell activity in the Drosophila testis.

PubMed

Tulina, Natalia M; Chen, Wen-Feng; Chen, Jung Hsuan; Sowcik, Mallory; Sehgal, Amita

2014-02-25

Adult stem cells maintain tissue integrity and function by renewing cellular content of the organism through regulated mitotic divisions. Previous studies showed that stem cell activity is affected by local, systemic, and environmental cues. Here, we explore a role of environmental day-night cycles in modulating cell cycle progression in populations of adult stem cells. Using a classic stem cell system, the Drosophila spermatogonial stem cell niche, we reveal daily rhythms in division frequencies of germ-line and somatic stem cells that act cooperatively to produce male gametes. We also examine whether behavioral sleep-wake cycles, which are driven by the environmental day-night cycles, regulate stem cell function. We find that flies lacking the sleep-promoting factor Sleepless, which maintains normal sleep in Drosophila, have increased germ-line stem cell (GSC) division rates, and this effect is mediated, in part, through a GABAergic signaling pathway. We suggest that alterations in sleep can influence the daily dynamics of GSC divisions.

Direct Analysis of JV-Curves Applied to an Outdoor-Degrading CdTe Module (Presentation)

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

Jordan, D; Kurtz, S.; Ulbrich, C.

2014-03-01

We present the application of a phenomenological four parameter equation to fit and analyze regularly measured current density-voltage JV curves of a CdTe module during 2.5 years of outdoor operation. The parameters are physically meaningful, i.e. the short circuit current density Jsc, open circuit voltage Voc and differential resistances Rsc, and Roc. For the chosen module, the fill factor FF degradation overweighs the degradation of Jsc and Voc. Interestingly, with outdoor exposure, not only the conductance at short circuit, Gsc, increases but also the Gsc(Jsc)-dependence. This is well explained with an increase in voltage dependent charge carrier collection in CdTe.

A GSC Global Genome Census (GSC8 Meeting)

ScienceCinema

Kyrpides, Nikos

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Nikos Kyrpides of the DOE Joint Genome Institute discusses the notion of a global genome census at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

A New Binary Star System of EW Type in Draco: GSC 03905-01870

NASA Astrophysics Data System (ADS)

Barquin, S.

2018-05-01

Discovery of a new binary star system (GSC 03905-01870 = USNO-B1.0 1431-0327922 = UCAC4 716-059522) in the Draco constellation is presented. It was discovered during a search for previously unreported eclipsing binary stars through the ASAS-SN database. The shape of the light curve and its characteristics (period of 0.428988+-0.000001 d, amplitude of 0.34+-0.02 V Mag, primary minimum epoch HJD 2457994.2756+-0.0002) indicates that the new variable star is an eclipsing binary of W Ursae Majoris type. I registered this variable star in The International Variable Star Index (VSX), its AAVSO UID is 000-BMP-891.

ASAS 095221-4329.8 und ASAS 123034-7703.9 - zwei R-CrB-Stern-Kandidaten aus der ASAS-Datenbank

NASA Astrophysics Data System (ADS)

Huemmerich, Stefan

2011-04-01

During an examination of ASAS Misc-type objects, the stars ASAS 095221-4329.8 GSC 07706-00560, 09:52:21.38 -43:29:40.5) and ASAS 123034-7703.9 (GSC 09416-00380, 12:30:34.22 -77:03:52.7) - both of which show semi-regular variability - were found to exhibit significant obscuration events in their V-band lightcurves. Both stars are likely to be red giants undergoing fading events, possibly of DY Per-type. However, spectroscopy of both stars is needed for a conclusive classification. The corresponding entries in the International Variable Star Index (VSX) have been revised accordingly; variability type was set to "RCB:".

Effect on Passive Range of Motion and Functional Correlates After a Long-Term Lower Limb Self-Stretch Program in Patients With Chronic Spastic Paresis.

PubMed

Pradines, Maud; Baude, Marjolaine; Marciniak, Christina; Francisco, Gerard; Gracies, Jean-Michel; Hutin, Emilie; Bayle, Nicolas

2018-03-02

In current health care systems, long-duration stretching, performed daily, cannot be obtained through prescriptions of physical therapy. In addition, the short-term efficacy of the various stretching techniques is disputed, and their long-term effects remain undocumented. To evaluate changes in extensibility in 6 lower limb muscles and in ambulation speed after a ≥1-year self-stretch program, the Guided Self-rehabilitation Contract (GSC), in individuals with chronic spastic paresis. Retrospective study comparing self-stretched and nonself-stretched muscles. Neurorehabilitation clinic. Patients diagnosed with hemiparesis or paraparesis at least 1 year before the initiation of a GSC and who were then involved in the GSC program for at least 1 year. For each patient, specific muscles were identified for intervention among the following: gluteus maximus, hamstrings, vastus, rectus femoris, soleus, and gastrocnemius. Prescriptions and training for a daily, high-load, prolonged, home self-stretching program were primarily based on the baseline coefficient of shortening, defined as C SH = [(X N -X V1 )/X N ] (X V1 = PROM, passive range of motion; X N = normally expected amplitude). Six assessments were performed per year, measuring the Tardieu X V1 or maximal slow stretch range of motion angle (PROM), C SH , 10-m ambulation speed, and its functional ambulation category (Perry's classification: household, limited, or full). Changes from baseline in self-stretched and nonself-stretched muscles were compared, with meaningful X V1 change defined as ΔX V1 >5° for plantar flexors and >10° for proximal muscles. Correlation between the composite X V1 (mean PROM for the 6 muscles) and ambulation speed also was evaluated. Twenty-seven GSC participants were identified (14 women, mean age 44 years, range 29-59): 18 with hemiparesis and 9 with paraparesis. After 1 year, 47% of self-stretched muscles showed meaningful change in PROM (ΔX V1 ) versus 14% in nonself-stretched muscles (P < .0001, χ 2 ). ΔC SH was -31% (95% confidence interval [95% CI] -41.5 to -15.2) in self-stretched versus -7% (95% CI -11.9 to -2.1) in nonself-stretched muscles (P < .0001, t-test). Ambulation speed increased by 41% (P < .0001) from 0.81 m/s (95% CI 0.67-0.95) to 1.15 m/s (95% CI 1.01-1.29). Eight of the 12 patients (67%) who were in limited or household categories at baseline moved to a higher functional ambulation category. There was a trend for a correlation between composite X V1 and ambulation speed (r = 0.44, P = .09) in hemiparetic patients. Therapists should consider prescribing and monitoring a long-term lower limb self-stretch program using GSC, as this may increase muscle extensibility in adult-onset chronic paresis. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

The Drosophila bag of marbles Gene Interacts Genetically with Wolbachia and Shows Female-Specific Effects of Divergence

PubMed Central

Flores, Heather A.; Bubnell, Jaclyn E.; Aquadro, Charles F.; Barbash, Daniel A.

2015-01-01

Many reproductive proteins from diverse taxa evolve rapidly and adaptively. These proteins are typically involved in late stages of reproduction such as sperm development and fertilization, and are more often functional in males than females. Surprisingly, many germline stem cell (GSC) regulatory genes, which are essential for the earliest stages of reproduction, also evolve adaptively in Drosophila. One example is the bag of marbles (bam) gene, which is required for GSC differentiation and germline cyst development in females and for regulating mitotic divisions and entry to spermatocyte differentiation in males. Here we show that the extensive divergence of bam between Drosophila melanogaster and D. simulans affects bam function in females but has no apparent effect in males. We further find that infection with Wolbachia pipientis, an endosymbiotic bacterium that can affect host reproduction through various mechanisms, partially suppresses female sterility caused by bam mutations in D. melanogaster and interacts differentially with bam orthologs from D. melanogaster and D. simulans. We propose that the adaptive evolution of bam has been driven at least in part by the long-term interactions between Drosophila species and Wolbachia. More generally, we suggest that microbial infections of the germline may explain the unexpected pattern of evolution of several GSC regulatory genes. PMID:26291077

Palaeoenvironmental implication of grain-size compositions of terrace deposits on the western Chinese Loess Plateau

NASA Astrophysics Data System (ADS)

Liu, Xingxing; Sun, Youbin; Vandenberghe, Jef; Li, Ying; An, Zhisheng

2018-06-01

Sedimentary sequences that developed on river terraces have been widely investigated to reconstruct high-resolution palaeoclimatic changes since the last deglaciation. However, frequent changes in sedimentary facies make palaeoenvironmental interpretation of grain-size variations relatively complicated. In this paper, we employed multiple grain-size parameters to discriminate the sedimentary characteristics of aeolian and fluvial facies in the Dadiwan (DDW) section on the western Chinese Loess Plateau. We found that wind and fluvial dynamics have quite different impacts on the grain-size compositions, with distinctive imprints on the distribution pattern. By using a lognormal distribution fitting approach, two major grain-size components sensitive to aeolian and fluvial processes, respectively, were distinguished from the grain-size compositions of the DDW terrace deposits. The fine grain-size component (GSC2) represents mixing of long-distance aeolian and short-distance fluvial inputs, whilst the coarse grain-size component (GSC3) is mainly transported by wind from short-distance sources. Thus GSC3 can be used to infer the wind intensity. Grain-size variations reveal that the wind intensity experienced a stepwise shift from large-amplitude variations during the last deglaciation to small-amplitude oscillations in the Holocene, corresponding well to climate changes from regional to global context.

EEG power during waking and NREM sleep in primary insomnia.

PubMed

Wu, You Meme; Pietrone, Regina; Cashmere, J David; Begley, Amy; Miewald, Jean M; Germain, Anne; Buysse, Daniel J

2013-10-15

Pathophysiological models of insomnia invoke the concept of 24-hour hyperarousal, which could lead to symptoms and physiological findings during waking and sleep. We hypothesized that this arousal could be seen in the waking electroencephalogram (EEG) of individuals with primary insomnia (PI), and that waking EEG power would correlate with non-REM (NREM) EEG. Subjects included 50 PI and 32 good sleeper controls (GSC). Five minutes of eyes closed waking EEG were collected at subjects' usual bedtimes, followed by polysomnography (PSG) at habitual sleep times. An automated algorithm and visual editing were used to remove artifacts from waking and sleep EEGs, followed by power spectral analysis to estimate power from 0.5-32 Hz. We did not find significant differences in waking or NREM EEG spectral power of PI and GSC. Significant correlations between waking and NREM sleep power were observed across all frequency bands in the PI group and in most frequency bands in the GSC group. The absence of significant differences between groups in waking or NREM EEG power suggests that our sample was not characterized by a high degree of cortical arousal. The consistent correlations between waking and NREM EEG power suggest that, in samples with elevated NREM EEG beta activity, waking EEG power may show a similar pattern.

Improved waste water treatment by bio-synthesized Graphene Sand Composite.

PubMed

Poornima Parvathi, V; Umadevi, M; Bhaviya Raj, R

2015-10-01

The photocatalytic and antibacterial properties of graphene biosynthesized from sugar and anchored on sand particles has been focused here. The morphology and composition of the synthesized Graphene Sand Composite (GSC) was investigated by means of X-ray powder diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDAX), Fourier Transform Infra-red Spectroscopy (FTIR) and UV-Visible spectroscopy. SEM images show wrinkly edges. This is characteristic of graphenic morphology. Three types of waste water samples namely, textile waste (TW), sugarcane industrial waste water (SW) and domestic waste water from a local purification center at Kodaikanal (KWW) were collected and treated. Adsorption experiments showed effective removal of impurities at 0.2 g of GSC. Photocatalytic activity was analyzed under visible and ultraviolet irradiation. The rate constant for TW increased to 0.0032/min for visible light irradiation from 0.0029/min under UV irradiation. SW showed similar improved activity with rate constant as 0.0023/min in visible irradiation compared to 0.0016/min under UV irradiation. For KWW enhanced activity was seen only in visible light irradiation with rate constant 0.0025/min. GSC showed an inhibition zone of 20 mm against the bacterium Escherichia coli. Results suggest development of economic and effective waste water management systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Tectonic-Magmatic Evolution of Galápagos Lineaments from Radiometric Dating and Bathymetry Along the Pinta-Marchena Ridge

NASA Astrophysics Data System (ADS)

Sinton, C.; Mittelstaedt, E. L.; Harpp, K. S.; Fornari, D. J.; Geist, D.; Soule, S. A.

2016-12-01

The Northern Galápagos Volcanic Province (NGVP), located north of the Galápagos Archipelago and centered across the 90° 50'W Galápagos transform fault (GTF) of the Galápagos Spreading Center (GSC), consists of a complex set of islands, seamount chains and ridges. The region is particularly important to deciphering the evolution of the Galápagos region as magmatism in this region is thought to be the result of interactions between the Galápagos mantle plume, the overlying lithosphere, and the GSC. To investigate the evolution of these interactions, we present seafloor images, bathymetry, and 40Ar-39Ar age data from a volcanic ridge that includes the islands of Pinta and Marchena. The most striking feature of this region is a flat-topped seamount, Banco Tuzo, with a shallow summit region reaching to 360-400 meters below sea level. Recovered basalt fragments from Banco Tuzo include sub-rounded rocks with morphologies that suggest exposure to a tidal environment. Ages of the lavas determined by 40Ar-39Ar dating vary from 2.0 Ma to 1.1 Ma (with 2σ error of ± 0.5 Ma). The subsidence rate calculated by the radiometric ages is similar to that estimated for young oceanic lithosphere. Our observations indicate that Banco Tuzo is an ancient, now submerged island. Other lavas recovered from the submarine flanks of Pinta and Marchena range in age from 1.4 to 0.6 Ma. These ages generally coincide with the westward propagation of the eastern GSC and the southward elongation of the GTF after a recent ridge jump ( 1 Ma), suggesting that magmatism along this ridge is related to the changing relative location of GSC and the upwelling Galapagos mantle plume.

Age-related differences in BOLD modulation to cognitive control costs in a multitasking paradigm: Global switch, local switch, and compatibility-switch costs.

PubMed

Nashiro, Kaoru; Qin, Shuo; O'Connell, Margaret A; Basak, Chandramallika

2018-05-15

It is well documented that older adults recruit additional brain regions compared to those recruited by younger adults while performing a wide variety of cognitive tasks. However, it is unclear how such age-related over-recruitment interacts with different types of cognitive control, and whether this over-recruitment is compensatory. To test this, we used a multitasking paradigm, which allowed us to examine age-related over-activation associated with three types of cognitive costs (i.e., global switch, local switch, compatibility-switch costs). We found age-related impairments in global switch cost (GSC), evidenced by slower response times for maintaining and coordinating two tasks vs. performing only one task. However, no age-related declines were observed in either local switch cost (LSC), a cognitive cost associated with switching between the two tasks while maintaining two task loads, or compatibility-switch cost (CSC), a cognitive cost associated with incompatible vs. compatible stimulus-response mappings across the two tasks. The fMRI analyses allowed for identification of distinct cognitive cost-sensitive brain regions associated with GSC and LSC. In fronto-parietal GSC and LSC regions, older adults' increased activations were associated with poorer performance (greater costs), whereas a reverse relationship was observed in younger adults. Older adults also recruited additional fronto-parietal brain regions outside the cognitive cost-sensitive areas, which was associated with poorer performance or no behavioral benefits. Our results suggest that older adults exhibit a combination of inefficient activation within cognitive cost-sensitive regions, specifically the GSC and LSC regions, and non-compensatory over-recruitment in age-sensitive regions. Age-related declines in global switching, compared to local switching, was observed earlier in old age at both neural and behavioral levels. Copyright © 2018 Elsevier Inc. All rights reserved.

Metallicity Effects on Stellar Magnetic Activity: Blanco 1 as a Test Case

NASA Technical Reports Server (NTRS)

Harnden, F. R., Jr.; Mushotzky, Richard F. (Technical Monitor)

2003-01-01

We present X-ray Luminosity Distributions (XLDs) of late-type members (dF, dG, dK, dM) of the Blanco 1 cluster, based on ROSAT-HRI data and new astrometric-photometric membership obtained from the GSC-II project. For the first time we present the XLD of dM stars of this cluster. The high metallicity of Blanco 1 allows us to investigate the role of chemical composition on the coronal emission of late-type stars. Comparison between X-ray Luminosity Distributions of Blanco 1 and Pleiades, NGC2516 and alpha Per suggests a possible metallicity effect in dM stars.

Report on DOE support for GSC13 travel award

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

Gilbert, Jack Anthony

2012-04-18

Consortium. The 3-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5-7th, 2012, and was hosted by the Beijing Genomics Institute (BGI). The meeting was entitled ‘From Genomes to Interactions to Communities to Models’ and aimed to be a scientific meeting that highlighted the role of data standards associated with genomic, metagenomic and amplicon sequence data, and the contextual information associated with the sample that data was generated from. To this end the meeting focused on genomic projects for animals, plants, fungi and viruses, metagenomic studies in host-microbe interactions, and community dynamics in microbial communities. Inmore » addition the meeting hosted a Genomic Observatories Network session, a GSC biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundation. The meeting was very well organized by the local hosts at BGI, and all attendees reported that they were very happy with the outcome, service and quality of the science presented. Highlights were keynotes by Rita Colwell, Mitch Sogin and Jim Tiedje. The 5 attendees paid for by the DOE award were Daniel Smith and Jared Wilkening (University of Chicago); Patrick Chain (Los Alamos National Laboratory), Austin Davis-Richardson (University of Florida) and Greg Caporoaso (University of Northern Arizona). Each attendee was able to either present or become involved with the attending scientists, and each reported that they had got something significant out of the meeting. Here are detailed their personal accounts of the GSC13 meeting. We thank DOE for the helping to fund this valuable outreach initiative, and for supporting the attendance of these bright young scientists at this important meeting.« less

[Experimental study of glioma stem cell-mediated immune tolerance in tumor microenvironment].

PubMed

Xie, T; Ma, J W; Liu, B; Dong, J; Huang, Q

2017-11-23

Objective: To investigate the tumor microenvironment of immune tolerance induced by glioma stem cells (GSC). Methods: Human GSC SU3 cells transfected with red fluorescent protein (SU3-RFP) gene were implanted into the brain, subcutis (armpit and foot), liver and abdominal cavity of transgenic green fluorescence protein (GFP) nude mice to establish RFP(+) /GFP(+) dual fluorescence solid tumor model. The re-cultured cells derived from implanted tumor tissues, SU3-RFP cells co-cultured with peritoneal fluid of transgenic GFP nude mice and malignant ascites of tumor-bearing mice were observed by fluorescence microscopy and real-time video image tracing to analyze the microenvironment of immune tolerance mediated by RFP(+) /GFP(+) implanted tumor. Results: Dual fluorescence labeled frozen section showed that all of cells in the tumor microenvironment were GFP(+) , while the pressed tissue-patch showed that the tumor blood vessels exhibited a RFP(+) /GFP(+) double-positioning yellow. In the GFP single fluorescence labeled tumor tissue, all of cells in the microenvironment were green, including tumor edge, necrotic foci and blood vessel. Among them, CD68(+) , F4/80(+) , CD11c(+) , CD11b(+) and CD80(+) cells were observed. In the dual fluorescence labeled co-cultured cells, the phagocytosis and fusion between green host cells and red tumor cells were also observed, and these fusion cells might transfer to the malignant dendritic cells and macrophages. Conclusions: The tumor microenvironment of immune tolerance induced by GSC is not affected by the tissue types of tumor-inoculated sites, and the immune tolerance mediated by inflammatory cells is associated with the inducible malignant transformation, which may be driven by cell fusion.

IDH1 mutation diminishes aggressive phenotype in glioma stem cells.

PubMed

Yao, Qi; Cai, Gang; Yu, Qi; Shen, Jianhong; Gu, Zhikai; Chen, Jian; Shi, Wei; Shi, Jinlong

2018-01-01

The R132H mutation in isocitrate dehydrogenase 1 (IDH1-R132H) is associated with better prognosis in glioma patients. Glioma stem cells (GSCs) in glioma are believed to be responsible for glioma growth and maintenance. However, the relation between the R132H mutation and GSCs is not fully understood. In the present study, GSC markers were detected in patients with IDH1-R132H or wild-type IDH1 (IDH1-wt) by tissue microarray immunohistochemistry (TMA-IHC). The relationship between the expression patterns of GSC markers and the clinicopathological characteristics in glioma were analyzed. To confirm this mutation's role in GSCs, the IDH1-R132H in GSCs isolated from glioblastoma patients with IDH1 mutations was overexpressed by using lentiviral constructs in vitro, and then the proliferation, differentiation, apoptosis, migration and invasion of the transfected GSCs were explored. At the molecular level, we detected Wnt/β-catenin signaling expression to verify its role in regulating the cellular properties of GSCs. The results showed that the positive rate of GSCs in patients with IDH1-R132H was significantly less than that in patients with IDH1-wt. The positive rate of GSCs was correlated with IDH1 mutation, TNM stage and poor overall survive. After transfection in vitro, IDH1-R132H overexpression led to reduced GSCs proliferation, migration and invasion, inducing apoptosis and improving GSC differentiation, accompanied by a significant reduction in activity of β-catenin. Several mediators, effectors and targets of the Wnt/β-catenin signaling were downregulated. The data demonstrate that IDH1 mutation reduces the malignant progression of glioma by causing a less aggressive phenotype of GSCs which are involved in the Wnt/β‑catenin signaling.

Effect of concentrate supplementation during the dry period on colostrum quality and effect of colostrum feeding regimen on passive transfer of immunity, calf health, and performance.

PubMed

Dunn, A; Ashfield, A; Earley, B; Welsh, M; Gordon, A; McGee, M; Morrison, S J

2017-01-01

The objectives were to evaluate the effect of (1) supplementing concentrates to multiparous Holstein cows during the dry period on colostral and milk immunoglobulin G (IgG) concentration; and (2) feeding calves colostrum at either 5 or 10% of their body weight (BW) on passive transfer of immunity, health, and performance. Holstein multiparous cows (n=37) were assigned to 1 of 2 nutritional treatments during an 8-wk dry period: (1) offered ad libitum grass silage only (GS) or (2) offered ad libitum access to the same grass silage plus concentrate [total mixed ration in a 75:25 dry matter (DM) ratio], providing a mean concentrate DM intake of 3.0kg/cow per day (GSC). Both treatment groups were offered identical levels of mineral and vitamin supplementation. Calves from these cows were weighed immediately after birth and fed either 5% (5BW) or 10% (10BW) of their BW in colostrum from their own dams within 2.5h of birth. Calves in the 10BW group received their second feed of colostrum from first-milking colostrum. Concentrate supplementation during the dry period had no effect on colostral IgG concentration, first-milking IgG yield, or fat, protein, and lactose contents. However, cows in GSC produced a greater mean milk yield over the first 8 milkings compared with cows in the GS group. Concentrate supplementation had no effect on calf BW or BW gain, serum IgG, or apparent efficiency of absorption (AEA) at 24h after birth. However, offspring from the GSC group had fewer cases of enteritis during the first 56d of life compared with offspring from the GS group. Calves in the 10BW group had greater mean serum IgG concentration for the first 3d following birth; however, at 24h after birth, we observed no treatment effect on AEA. The rate of enteritis was greater for calves in the 5BW treatment compared with 10BW. The colostrum-feeding regimen had no effect on BW gain or on the incidence of pneumonia among calf treatment groups. In conclusion, concentrate supplementation regimens offered during the dry period had a positive effect on colostrum yield, and offspring from the GSC group had a reduced rate of enteritis. Feeding 10% of BW of colostrum versus 5% of BW resulted in a greater serum IgG concentration for the first 3d postpartum, and 10BW calves had a reduced rate of enteritis. Overall, to achieve successful passive transfer, decrease the rate of enteritis, and increase efficiency in the dairy calf, we recommend that dairy calves be fed 10% of their BW in colostrum as soon as possible after birth. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The minimum information about a genome sequence (MIGS) specification

PubMed Central

Field, Dawn; Garrity, George; Gray, Tanya; Morrison, Norman; Selengut, Jeremy; Sterk, Peter; Tatusova, Tatiana; Thomson, Nicholas; Allen, Michael J; Angiuoli, Samuel V; Ashburner, Michael; Axelrod, Nelson; Baldauf, Sandra; Ballard, Stuart; Boore, Jeffrey; Cochrane, Guy; Cole, James; Dawyndt, Peter; De Vos, Paul; dePamphilis, Claude; Edwards, Robert; Faruque, Nadeem; Feldman, Robert; Gilbert, Jack; Gilna, Paul; Glöckner, Frank Oliver; Goldstein, Philip; Guralnick, Robert; Haft, Dan; Hancock, David; Hermjakob, Henning; Hertz-Fowler, Christiane; Hugenholtz, Phil; Joint, Ian; Kagan, Leonid; Kane, Matthew; Kennedy, Jessie; Kowalchuk, George; Kottmann, Renzo; Kolker, Eugene; Kravitz, Saul; Kyrpides, Nikos; Leebens-Mack, Jim; Lewis, Suzanna E; Li, Kelvin; Lister, Allyson L; Lord, Phillip; Maltsev, Natalia; Markowitz, Victor; Martiny, Jennifer; Methe, Barbara; Mizrachi, Ilene; Moxon, Richard; Nelson, Karen; Parkhill, Julian; Proctor, Lita; White, Owen; Sansone, Susanna-Assunta; Spiers, Andrew; Stevens, Robert; Swift, Paul; Taylor, Chris; Tateno, Yoshio; Tett, Adrian; Turner, Sarah; Ussery, David; Vaughan, Bob; Ward, Naomi; Whetzel, Trish; Gil, Ingio San; Wilson, Gareth; Wipat, Anil

2008-01-01

With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the ‘transparency’ of the information contained in existing genomic databases. PMID:18464787

MAXI/GSC 7-year Source Catalog

NASA Astrophysics Data System (ADS)

Ueda, Y.; Kawamuro, T.; Hori, T.; Shidatsu, M.; Tanimoto, A.; MAXI Team

2017-10-01

Monitor of All-sky X-ray Image (MAXI) on the International Space Station has been continuously observing the X-ray sky since its launch in 2009. The MAXI survey has achieved the best sensitivity in the 4-10 keV band as an all sky X-ray mission, and is complementary to the ROSAT all sky survey (<2 keV) and hard X-ray (>10 keV) surveys performed with Swift and INTEGRAL. Here we present the latest source catalog of MAXI/Gas Slit Camera (GSC) constructed from the first 7-year data, which is an extension of the 37-month catalog of the high Galactic-latitude sky (Hiroi et al. 2013). We summarize statistical properties of the X-ray sources and results of cross identification with other catalogs.

WCSTools 3.0: More Tools for Image Astrometry and Catalog Searching

NASA Astrophysics Data System (ADS)

Mink, Douglas J.

For five years, WCSTools has provided image astrometry for astronomers who need accurate positions for objects they wish to observe. Other functions have been added and improved since the package was first released. Support has been added for new catalogs, such as the GSC-ACT, 2MASS Point Source Catalog, and GSC II, as they have been published. A simple command line interface can search any supported catalog, returning information in several standard formats, whether the catalog is on a local disk or searchable over the World Wide Web. The catalog searching routine can be located on either end (or both ends!) of such a web connection, and the output from one catalog search can be used as the input to another search.

Culturally sensitive substance abuse intervention for Hispanic and African American adolescents: empirical examples from the Alcohol Treatment Targeting Adolescents in Need (ATTAIN) Project.

PubMed

Gil, Andrés G; Wagner, Eric F; Tubman, Jonathan G

2004-11-01

This study presents preliminary analyses examining the effects of an alcohol and other drug use (AOD) intervention with minority juvenile offenders. Furthermore, the study investigates the impact of cultural factors on baseline AOD use among Hispanic and African American youth, as well as on treatment outcome. Participants were 213 juvenile offenders referred for treatment (mean age = 15.7 years), 97 of whom have completed treatment to date. The intervention was carried out in clinics placed within the neighborhoods in which the participants resided. Intervention Alcohol Treatment Targeting Adolescents in Need (ATTAIN) is a controlled clinical trial evaluating the effectiveness of a brief motivational, cognitive behavioral intervention, guided self-change (GSC). Participants are assigned randomly to the individual format of guided self-change (I-GSC), the family involved format of guided self-Change (F-GSC), choice of one of these two, or a waiting list control condition. Only participants involved in active intervention are included in the present report. Data were collected via structured face-to-face interviews. Alcohol and marijuana use measures were collected using the Time-line Follow-back interview (TLFB). There were significant reductions in alcohol and marijuana use for all ethnic groups from baseline to post-intervention. Cultural factors (discrimination, acculturation, ethnic pride and cultural mistrust) were associated with pre-intervention levels of alcohol and marijuana use. Among Hispanics, pre-intervention level of substance use were higher among foreign-born than US-born youth. Analyses conducted with the US-born Hispanic group showed that ethnic orientation and ethnic pride were associated positively with greater reductions in alcohol use. The intervention provided through ATTAIN appears to be effective with a multi-ethnic population of juvenile delinquents. Cultural factors, such as ethnic orientation and ethnic mistrust, appear to constitute amenability to treatment factors, with US-born Hispanic youth lower in acculturation responding better to the intervention.

Histone H3K9 Trimethylase Eggless Controls Germline Stem Cell Maintenance and Differentiation

PubMed Central

Zhou, Jian; McDowell, William; Park, Jungeun; Haug, Jeff; Staehling, Karen; Tang, Hong; Xie, Ting

2011-01-01

Epigenetic regulation plays critical roles in the regulation of cell proliferation, fate determination, and survival. It has been shown to control self-renewal and lineage differentiation of embryonic stem cells. However, epigenetic regulation of adult stem cell function remains poorly defined. Drosophila ovarian germline stem cells (GSCs) are a productive adult stem cell system for revealing regulatory mechanisms controlling self-renewal and differentiation. In this study, we show that Eggless (Egg), a H3K9 methyltransferase in Drosophila, is required in GSCs for controlling self-renewal and in escort cells for regulating germ cell differentiation. egg mutant ovaries primarily exhibit germ cell differentiation defects in young females and gradually lose GSCs with time, indicating that Egg regulates both germ cell maintenance and differentiation. Marked mutant egg GSCs lack expression of trimethylated H3K9 (H3k9me3) and are rapidly lost from the niche, but their mutant progeny can still differentiate into 16-cell cysts, indicating that Egg is required intrinsically to control GSC self-renewal but not differentiation. Interestingly, BMP-mediated transcriptional repression of differentiation factor bam in marked egg mutant GSCs remains normal, indicating that Egg is dispensable for BMP signaling in GSCs. Normally, Bam and Bgcn interact with each other to promote GSC differentiation. Interestingly, marked double mutant egg bgcn GSCs are still lost, but their progeny are able to differentiate into 16-cell cysts though bgcn mutant GSCs normally do not differentiate, indicating that Egg intrinsically controls GSC self-renewal through repressing a Bam/Bgcn-independent pathway. Surprisingly, RNAi-mediated egg knockdown in escort cells leads to their gradual loss and a germ cell differentiation defect. The germ cell differentiation defect is at least in part attributed to an increase in BMP signaling in the germ cell differentiation niche. Therefore, this study has revealed the essential roles of histone H3K9 trimethylation in controlling stem cell maintenance and differentiation through distinct mechanisms. PMID:22216012

Apigenin Inhibits Cancer Stem Cell-Like Phenotypes in Human Glioblastoma Cells via Suppression of c-Met Signaling.

PubMed

Kim, Boram; Jung, Narae; Lee, Sanghun; Sohng, Jae Kyung; Jung, Hye Jin

2016-11-01

Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self-renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell-like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self-renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem-like cells. Notably, apigenin blocked the phosphorylation of c-Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen-activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c-Met signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXM1-Dependent Manner

PubMed Central

Kim, Sung-Hak; Joshi, Kaushal; Ezhilarasan, Ravesanker; Myers, Toshia R.; Siu, Jason; Gu, Chunyu; Nakano-Okuno, Mariko; Taylor, David; Minata, Mutsuko; Sulman, Erik P.; Lee, Jeongwu; Bhat, Krishna P.L.; Salcini, Anna Elisabetta; Nakano, Ichiro

2015-01-01

Summary Glioblastoma (GBM)-derived tumorigenic stem-like cells (GSCs) may play a key role in therapy resistance. Previously, we reported that the mitotic kinase MELK binds and phosphorylates the oncogenic transcription factor FOXM1 in GSCs. Here, we demonstrate that the catalytic subunit of Polycomb repressive complex 2, EZH2, is targeted by the MELK-FOXM1 complex, which in turn promotes resistance to radiation in GSCs. Clinically, EZH2 and MELK are coexpressed in GBM and significantly induced in postirradiation recurrent tumors whose expression is inversely correlated with patient prognosis. Through a gain-and loss-of-function study, we show that MELK or FOXM1 contributes to GSC radioresistance by regulation of EZH2. We further demonstrate that the MELK-EZH2 axis is evolutionarily conserved in Caenorhabditis elegans. Collectively, these data suggest that the MELK-FOXM1-EZH2 signaling axis is essential for GSC radioresistance and therefore raise the possibility that MELK-FOXM1-driven EZH2 signaling can serve as a therapeutic target in irradiation-resistant GBM tumors. PMID:25601206

First photometric study of the W UMa system GSC 1042-2191

NASA Astrophysics Data System (ADS)

Bulut, A.; Bulut, İ.; Demircan, O.

2016-04-01

We present new photometric observations covering eight minima times for the eclipsing binary GSC 1042-2191. The light curves in BVRI colors were analyzed by using WD-code for the system parameters. Eight minima times were obtained from the new observations. The system is found a low mass ratio (q = 0.148), A-type over-contact binary with a fill out parameter of f = 65.01 ± 12.18%. The preliminary absolute dimensions (M1= 1.26 ± 0.06 M⊙, M2 = 0.18 ± 0.06 M⊙, R1 = 1.54 ± 0.20 R⊙, R2 = 0.69 ± 0.01 R⊙, L1 =3.30 ± 0.30 L⊙ and L2 = 0.59 ± 0.20 L⊙) indicate the very much oversized and over-luminous secondary component, by assuming the present luminosity of the secondary is its main sequence luminosity, we predict the original mass is about 0.8 M⊙, this means the present secondary could be transferred and/or lost 77% of its original mass and only its core is left.

The generalized scattering coefficient method for plane wave scattering in layered structures

NASA Astrophysics Data System (ADS)

Liu, Yu; Li, Chao; Wang, Huai-Yu; Zhou, Yun-Song

2017-02-01

The generalized scattering coefficient (GSC) method is pedagogically derived and employed to study the scattering of plane waves in homogeneous and inhomogeneous layered structures. The numerical stabilities and accuracies of this method and other commonly used numerical methods are discussed and compared. For homogeneous layered structures, concise scattering formulas with clear physical interpretations and strong numerical stability are obtained by introducing the GSCs. For inhomogeneous layered structures, three numerical methods are employed: the staircase approximation method, the power series expansion method, and the differential equation based on the GSCs. We investigate the accuracies and convergence behaviors of these methods by comparing their predictions to the exact results. The conclusions are as follows. The staircase approximation method has a slow convergence in spite of its simple and intuitive implementation, and a fine stratification within the inhomogeneous layer is required for obtaining accurate results. The expansion method results are sensitive to the expansion order, and the treatment becomes very complicated for relatively complex configurations, which restricts its applicability. By contrast, the GSC-based differential equation possesses a simple implementation while providing fast and accurate results.

Research Note PSR B1929+10 and GSC 01060-01374 are not binary companions

NASA Astrophysics Data System (ADS)

Kouwenhoven, M. L. A.; van den Berg, M. C.

2001-03-01

We have observed the star GSC 01060-01374 to investigate whether it is in a binary with PSR B1929+10. Its spectral type is K4-6 and its luminosity class is III or II, therefore its distance is 2.4 kpc or higher. Since the dispersion measure distance of PSR B1929+10 is 0.17 kpc, we rule out the possibility that these two stars are associated in a binary. This poses further constraints on the lower limit of kick velocities in supernova explosions. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias.

A Large Lunar Surface Testbed from Low Cost Material

NASA Technical Reports Server (NTRS)

Rickman, Douglas

2014-01-01

For users needing to simulate the lunar surface, several distinct avenues have been used. Numerous volcanic areas, including Hawaii, have been used. While providing very large areas and scenic interest, field parties to such an area is expensive and limits testing time. An alternative is to build test facilities locally. This has been done many ways, contrast GRC-1, GSC-1, BP-1 and the KSC Morpheus facility [1-4]. GRC-1 is a mixture of sand and clay; GSC-1 and BP-1 are waste materials created in the process of crushing basaltic rock. The Morpheus field used salvaged concrete and crushed quartz rock [5]. Here I report about a 30 m X 30 m test area at MSFC which was both low cost and relatively high fidelity [6].

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

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

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequencemore » (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

DOE PAGES

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas; ...

2017-08-08

Here, we present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a MetagenomeAssembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Genemore » Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

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

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

Here, we present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a MetagenomeAssembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Genemore » Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

MAXI/GSC detection of a rapid X-ray brightening from Mrk 421

NASA Astrophysics Data System (ADS)

Tachibana, Y.; Ueda, Y.; Negoro, H.; Ueno, S.; Tomida, H.; Ishikawa, M.; Sugawara, Y.; Isobe, N.; Shimomukai, R.; Mihara, T.; Sugizaki, M.; Nakahira, S.; Iwakiri, W.; Shidatsu, M.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugita, S.; Yoshii, T.; Harita, S.; Muraki, Y.; Morita, K.; Yoshida, A.; Sakamoto, T.; Serino, M.; Kawakubo, Y.; Kitaoka, Y.; Hashimoto, T.; Tsunemi, H.; Yoneyama, T.; Nakajima, M.; Kawase, T.; Sakamaki, A.; Hori, T.; Tanimoto, A.; Oda, S.; Morita, T.; Yamada, S.; Tsuboi, Y.; Nakamura, Y.; Sasaki, R.; Kawai, H.; Sato, T.; Yamauchi, M.; Hanyu, C.; Hidaka, K.; Kawamuro, T.; Yamaoka, K.

2018-01-01

MAXI/GSC is detecting a bright X-ray flare from the BL Lac object Mrk 421. The MAXI daily fluxes for the last 5 days are following: MJD & emsp; 2-4 keV (mCrab) & emsp; 4-10 keV (mCrab) 58131 & emsp; 53 +- 5 & emsp; 52 +- 6 58132 & emsp; 34 +- 5 & emsp; 29 +- 5 58133 & emsp; 56 +- 5 & emsp; 53 +- 6 58134 & emsp; 91 +- 7 & emsp; 98 +- 7 58135 & emsp; 106 +- 8 & emsp; 124 +- 9 The current flux is comparable with the peak daily flux in the brightest X-ray flare from this object ever since the beginning of the MAXI observation (156 +- 11 mCrab in 1.5-10 keV on 2010 February 16, ATEL #2444; Isobe et al. 2010 PASJ 52, L55), and the X-ray brightening is still ongoing.

Analysis of GSC 2475-1587 and GSC 841-277: Two Eclipsing Binary Stars Found During Asteroid Lightcurve Observations

NASA Astrophysics Data System (ADS)

Stephens, R. D.; Warner, B. D.

2006-05-01

When observing asteroids we select from two to five comparison stars for differential photometry, taking the average value of the comparisons for the single value to be subtracted from the value for the asteroid. As a check, the raw data of each comparison star are plotted as is the difference between any single comparison and the average of the remaining stars in the set. On more than one occasion, we have found that at least one of the comparisons was variable. In two instances, we took time away from our asteroid lightcurve work to determine the period of the two binaries and attempted to model the system using David Bradstreet's Binary Maker 3. Unfortunately, neither binary showed a total eclipse. Therefore, our results are not conclusive and present only one of many possibilities.

GSC4813-0981 = V921 Mon, a new low-amplitude δ Scuti star with variable amplitude

NASA Astrophysics Data System (ADS)

Galeev, A.; Bikmaev, I.; Shimansky, V.; Deminova, N.

2014-11-01

GSC 4813-0981 = V921 Mon is a low-amplitude δ Scuti-type variable with an amplitude of 0.018^m-0.027^m in different bands and a period of 48.5 minutes. The fundamental parameters of the atmosphere and physical characteristics, determined from medium-resolution spectra, are: T_{eff}=8700 K, log g=3.95 dex, [M/H]=0, M=1.7 M_{⊙}, R=2.3 R_{⊙}. We performed a long-term analysis of the variations using a ten-year data set of CCD observations (2003-2013) acquired in BVR with the 1.5-m Russian-Turkish telescope (RTT150, TUBITAK National Observatory). A preliminary result is that the amplitude of the variability changes; it was decreasing during 2003-2008, but is now increasing.

VizieR Online Data Catalog: The Initial Gaia Source List (IGSL) (Smart, 2013)

NASA Astrophysics Data System (ADS)

Smart, R. L.; Nicastro, L.

2013-11-01

The IGSL is a compilation catalog produced for the Gaia mission. We have combined data from the following catalogs or datasets to produce a homogenous list of positons, proper motions, photometry in a blue and red band and estimates of the magnitudes in the Gaia G and G_RVS bands. Included Catalogs: Tycho2, LQRF, UCAC4, SDSS-DR9, PPMXL, GSC23, GEPC, OGLE, Sky2000, 2MASS. Note that in compiling the various entries we did not consider the individual flags. Overall, we think this catalog is reliable but there will be errors, mismatches and duplicates. The user should use this catalog with that in mind, it is fine for statistical studies that has some way to remove obviously incorrect entries but it should only be used with care for individual objects. The source catalogs used to produce the IGSL are: * The Gaia Ecliptic Pole Catalog, version 3.0 (GEPC) Altmann & Bastian 2009, "Ecliptic Poles Catalogue Version 1.1" ESA Document GAIA-C3-TN-ARI-MA-002 URL http://www.rssd.esa.int/llink/livelink/open/2885828 * GSC2.3: GSC2 version 2.3, Lasker et al. 2008AJ....136..735L (I/305) * an excerpt of the 4th version of the Gaia Initial QSO Catalog (GIQC) as compiled by the GWP-S-335-13000, formed by Alexandre H. Andrei, Christophe Barache, Dario N. da Silva Neto, Francois Taris, Geraldine Bourda, Jean-Francois Le Campion, Jean Souchay, J.J. Pereira Osorio, Julio I. Bueno de Camargo, Marcelo Assafin, Roberto Vieira Martins, Sebastien Bouquillon, Sebastien Lambert, Sonia Anton, Patrick Charlot * OGLE: Optical Gravitational Lensing Experiment version III (Szymaski et al., 2011, Cat. J/AcA/61/83) * PPMXL: Positions and Proper Motions "Extra Large" Catalog, Roeser et al. (2010, Cat. I/317) * SDSS: Sloan Digital Sky Survey data release 9, Cat. V/139 * UCAC4: Zacharias et al., 2012, Cat. I/322 * Tycho-2, Hoeg et al., 2000, Cat. I/259 (1 data file).

Challenges in Optical Emission Spectroscopy

NASA Astrophysics Data System (ADS)

Siepa, Sarah; Berger, Birk; Schulze, Julian; Schuengel, Edmund; von Keudell, Achim

2016-09-01

Collisional-radiative models (CRMs) are widely used to investigate plasma properties such as electron density, electron temperature and the form of the electron energy distribution function. In this work an extensive CRM for argon is presented, which models 30 excited states and various kinds of processes including electron impact excitation/de-excitation, radiation and radiation trapping. The CRM is evaluated in several test cases, i.e. inductively and capacitively coupled plasmas at various pressures, powers/voltages and gas admixtures. Deviations are found between modelled and measured spectra. The escape factor as a means of describing radiation trapping is discussed as well as the cross section data for electron impact processes. This work was supported by the Ruhr University Research School PLUS, funded by Germany's Excellence Initiative [DFG GSC 98/3].

ALIX and ESCRT-III Coordinately Control Cytokinetic Abscission during Germline Stem Cell Division In Vivo

PubMed Central

Eikenes, Åsmund H.; Malerød, Lene; Christensen, Anette Lie; Steen, Chloé B.; Mathieu, Juliette; Nezis, Ioannis P.; Liestøl, Knut; Huynh, Jean-René; Stenmark, Harald; Haglund, Kaisa

2015-01-01

Abscission is the final step of cytokinesis that involves the cleavage of the intercellular bridge connecting the two daughter cells. Recent studies have given novel insight into the spatiotemporal regulation and molecular mechanisms controlling abscission in cultured yeast and human cells. The mechanisms of abscission in living metazoan tissues are however not well understood. Here we show that ALIX and the ESCRT-III component Shrub are required for completion of abscission during Drosophila female germline stem cell (fGSC) division. Loss of ALIX or Shrub function in fGSCs leads to delayed abscission and the consequent formation of stem cysts in which chains of daughter cells remain interconnected to the fGSC via midbody rings and fusome. We demonstrate that ALIX and Shrub interact and that they co-localize at midbody rings and midbodies during cytokinetic abscission in fGSCs. Mechanistically, we show that the direct interaction between ALIX and Shrub is required to ensure cytokinesis completion with normal kinetics in fGSCs. We conclude that ALIX and ESCRT-III coordinately control abscission in Drosophila fGSCs and that their complex formation is required for accurate abscission timing in GSCs in vivo. PMID:25635693

Cardiovascular reactivity in a simulated job interview: the role of gender role self-concept.

PubMed

Sieverding, Monika; Weidner, Gerdi; von Volkmann, Bettina

2005-01-01

This study investigated the relation of gender role self-concept (G-SC) to cardiovascular and emotional reactions to an ecologically relevant stressor in a sample of graduating male and female university students. Thirty-seven men and 37 women completed the Personal Attribute Questionnaire and worked on four tasks designed to reflect common features of a job interview. Blood pressure and heart rate were measured at baseline, during, and after each task; subjective stress was measured at baseline and after each task. Subjective and objective stress scores were averaged across tasks and analyzed by sex and G-SC (i.e., instrumentality, expressiveness). Results indicated that women as a group demonstrated greater emotional reactivity, but did not differ in their physiological reactions when compared to men. Regardless of sex, participants' instrumentality scores contributed significantly to the variation in subjective stress response: those scoring high on instrumentality reported less stress, but evidenced greater blood pressure reactivity than those scoring low on instrumentality. These results suggest that gender roles, particularly an instrumental self-concept, may play an important role in both subjective and objective reactions to an ecologically relevant stressor.

Effect of the Galapagos Hotspot on Seamount Formation along the Galapagos Spreading Center

NASA Astrophysics Data System (ADS)

Behn, M. D.; Sinton, J. M.; Detrick, R. S.

2002-12-01

Studies along the Mid-Atlantic Ridge (MAR) and East Pacific Rise (EPR) have shown seamount formation to be a strong function of spreading rate. At the MAR, seamounts are a dominant morphologic feature of the inner valley floor, while at the EPR seamounts are rarely observed within the neovolcanic zone. The Galapagos Spreading Center (GSC) provides an excellent location to test the influence of a hotspot on the process of seamount generation at a relatively constant spreading rate. In this study we use multi-beam bathymetry data acquired during the G-PRIME cruise in April-May, 2000 to examine the distribution of axial seamounts along the GSC with distance from the hotspot. We use a numerical algorithm to identify isolated volcanic edifices, by searching bathymetry for closed, concentric contours protruding above the surrounding seafloor. Seamount populations are fit with a maximum likelihood model to estimate the total number of seamounts per unit area, ν o, and the characteristic seamount height, β-1. The number of seamounts in the axial zone decreases significantly as the Galapagos hotspot is approached, suggesting a change from dominantly point-source to fissure-fed volcanism as magma supply increases. West of the 95.5°W propagator, the total number of seamounts per unit area (ν o = 279+/-16 per 103 km2) is similar to values observed at the MAR. In comparison, east of 92.7°W, where magma supply is higher, seamount density (50+/-9 per 103 km2) is similar to observations at the fast-spreading EPR. Our results show that the transition from point-source to fissure-fed eruptions occurs gradually, in contrast to the "threshold" effect observed in axial magma chamber depth and axial morphology in which small changes in magma supply result in large changes in these variables. In summary, the western GSC displays the same range in seamount density observed along the global mid-ocean ridge system suggesting that both spreading rate and magma supply are important factors controlling the style of constructional volcanism (point source vs fissure fed eruptions) at oceanic spreading centers.

A standard MIGS/MIMS compliant XML Schema: toward the development of the Genomic Contextual Data Markup Language (GCDML).

PubMed

Kottmann, Renzo; Gray, Tanya; Murphy, Sean; Kagan, Leonid; Kravitz, Saul; Lombardot, Thierry; Field, Dawn; Glöckner, Frank Oliver

2008-06-01

The Genomic Contextual Data Markup Language (GCDML) is a core project of the Genomic Standards Consortium (GSC) that implements the "Minimum Information about a Genome Sequence" (MIGS) specification and its extension, the "Minimum Information about a Metagenome Sequence" (MIMS). GCDML is an XML Schema for generating MIGS/MIMS compliant reports for data entry, exchange, and storage. When mature, this sample-centric, strongly-typed schema will provide a diverse set of descriptors for describing the exact origin and processing of a biological sample, from sampling to sequencing, and subsequent analysis. Here we describe the need for such a project, outline design principles required to support the project, and make an open call for participation in defining the future content of GCDML. GCDML is freely available, and can be downloaded, along with documentation, from the GSC Web site (http://gensc.org).

Analysis of observations of the dwarf nova pegasi 2010

NASA Astrophysics Data System (ADS)

Shimansky, V. V.; Mitrofanova, A. A.; Borisov, N. V.; Gabdeev, M. M.

2013-06-01

Analysis of photometric and spectroscopic observations of GSC 02197-00886 at the outburst maximum (on May 8, 2010) and at the stage of relaxation towards the quiescent (on August 4, 2010) was performed. Radiation of an optically thick accretion disc with a hot boundary layer dominates the spectra, which are consistent with the spectra of a WZ Sge-type dwarf novae. In the relaxation phase, an optically thin accretion disc with radiation in the HI and HeI emission lines is observed against the background of the absorption spectrum of a white dwarf. The parameters of GSC 02197-00886, which were determined by combining the radial velocities of the components with the assumption that the secondary component is close to mainsequence stars, differ significantly from the parameters that characterize other WZ Sge-type systems. We hypothesize that the secondary component was excited in the course of the outburst and experienced long-lasting relaxation towards the main-sequence state.

Germline Stem Cells

PubMed Central

Spradling, Allan; Fuller, Margaret T.; Braun, Robert E.; Yoshida, Shosei

2011-01-01

Sperm and egg production requires a robust stem cell system that balances self-renewal with differentiation. Self-renewal at the expense of differentiation can cause tumorigenesis, whereas differentiation at the expense of self-renewal can cause germ cell depletion and infertility. In most organisms, and sometimes in both sexes, germline stem cells (GSCs) often reside in a defined anatomical niche. Factors within the niche regulate a balance between GSC self-renewal and differentiation. Asymmetric division of the germline stem cell to form daughter cells with alternative fates is common. The exception to both these tendencies is the mammalian testis where there does not appear to be an obvious anatomical niche and where GSC homeostasis is likely accomplished by a stochastic balance of self-renewal and differentiation and not by regulated asymmetric cell division. Despite these apparent differences, GSCs in all organisms share many common mechanisms, although not necessarily molecules, to guarantee survival of the germline. PMID:21791699

Promyelocytic leukaemia zinc finger maintains self-renewal of male germline stem cells (mGSCs) and its expression pattern in dairy goat testis.

PubMed

Song, W; Zhu, H; Li, M; Li, N; Wu, J; Mu, H; Yao, X; Han, W; Liu, W; Hua, J

2013-08-01

Previous studies have shown that promyelocytic leukaemia zinc finger (PLZF) is a spermatogonia-specific transcription factor in the testis, required to regulate self-renewal and maintenance of the spermatogonia stem cell. Up to now, expression and function of PLZF in the goat testis has not been known. The objectives of this study were to investigate PLZF expression pattern in the dairy goat and its effect on male goat germline stem cell (mGSC) self-renewal and differentiation. Testis development and expression patterns of PLZF in the dairy goat were analysed by haematoxylin and eosin staining, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, effects of PLZF overexpression on mGSC self-renewal and differentiation were evaluated by quantitative RT-PCR (QRT-PCR), immunofluorescence and BrdU incorporation assay. Promyelocytic leukaemia zinc finger was essential for dairy goat testis development and expression of several proliferation and pluripotency-associated proteins including OCT4, C-MYC were upregulated by PLZF overexpression. The study demonstrated that PLZF played a key role in maintaining self-renewal of mGSCs and its overexpression enhanced expression of proliferation-associated genes. Promyelocytic leukaemia zinc finger could function in the dairy goat as well as in other species in maintaining self-renewal of germline stem cells and this study provides a model to study the mechanism on self-renewal and differentiation of mGSCs in livestock. © 2013 John Wiley & Sons Ltd.

Geophysical constraints on the compensation mechanism of the Galápagos swell

NASA Astrophysics Data System (ADS)

Canales, J.; Ito, G.; Detrick, R. S.; Sinton, J. M.

2001-12-01

We use geophysical observations such as bathymetry, gravity, and seismic crustal thickness to understand the origin of the Galápagos swell. Wide-angle refraction and multichannel reflection seismic data show that the crust along the Galápagos Spreading Center (GSC) between 97.5° W and 91° W thickens by 2.3 km as the Galápagos plume is approached from the west [Ito et al., this meeting]. Axial depth along the GSC shoals by 1800 m, 60% of which is due to dynamic topography and changes in axial morphology. The remaining 700 m correspond to the amplitude of the Galápagos bathymetric swell, 75% of which is explained by crustal thickening. The eastward shoaling of the swell and increase in crustal thickness along the GSC is accompained by a progressive decrease in mantle Bouguer gravity anomaly (MBA). Assuming a constant crustal thickness model, the MBA reaches a minimum value of -70 mGal near 91.25° W. After correcting for changes in crustal thickness, however, the gravity anomaly shows a minimum of -25 mGal near 92.2° W, the area where the GSC is intersected by the Wolf-Darwin volcanic lineament. We attribute the remaining 25% of swell bathymetry and 35% of gravity anomaly to an eastward reduction of mantle density above an effective compensation depth, constrained to be 50-200 km. Simple melting calculations assuming passive mantle upwelling predict that the observed crustal thickenning is consistent with a small eastward increase in mantle temperature of 15-25 ° C. This thermal anomaly produces an eastward decrease in mantle density due to thermal expansion and the subsequent along-axis variation in melt depletion. For preferred mantle compensation depths of 50-150 km the thermal effects can explain 40 to 70% of the mantle density anomaly required by the geophysical observations. Therefore, our results require the existence of compositionally-buoyant mantle beneath the GCS near the Galápagos plume. We will discuss plausible origins for the mantle anomaly such as depleted mantle by the upwelling plume, melt retention, or a mantle source enriched in incompatible elements and volatiles [Cushman et al., this meeting], and their implications for melting beneath the Galápagos plume-ridge system.

Signs of Recent Volcanism and Hydrothermal Activity Along the Eastern Segment of the Galapagos Spreading Center

NASA Astrophysics Data System (ADS)

Raineault, N.; Smart, C.; Mayer, L. A.; Ballard, R. D.; Fisher, C. R.; Marsh, L.; Shank, T. M.

2016-12-01

Since the initial discovery of the Galápagos Spreading Center (GSC) vents in 1977, large-scale disturbances resulting from eruptive and tectonic activity have both destroyed and created vent habitats along the GSC. In 2015, the E/V Nautilus returned to the GSC with remotely operated vehicles (ROVs) to explore 17 kilometers of the rift valley from the Rosebud site in the west, to a previously unexplored temperature anomaly east of the Tempus Fugit vent site. In the years to over a decade since scientists last visited the Rosebud, Rose Garden, and Tempus Fugit sites, there were many changes. Most notably, the Rosebud site, where scientists found a nascent vent community and left site markers in 2002, was apparently covered with glassy basaltic sheet flows. In addition to visual exploration, oceanographic sensor measurements and direct sampling, we used the ROV Hercules imaging suite, comprised of stereo cameras and a structured light laser sensor to map an area of diffuse flow in the Tempus Fugit field (100 m x 150 m). The centimeter-level photographic and bathymetric maps created with this system, along with ROV HD video, samples, and environmental sensors, documented hydrothermal activity and changes in biological community structure (e.g., Riftia tubeworms observed in nascent stages of community development in 2011 were now, in 2015, in greater abundance (with tubes almost 4 m in length). The detection of active venting and associated faunal assemblages will provide insight into the temporal and spatial variability of venting activity at the Tempus Fugit site. On a visual survey of the Rift east of the Tempus Fugit site, extinct sulfide chimney structures were discovered and sampled. There were several chimneys and sulfide deposits in a span of over 8 km that ranged in height from over a half meter to 1.5 m tall. Diffuse flow hosting white and blue bacterial mats was observed near the chimneys complexes. The base of a large chimney structure, venting white fluids, as well as adjacent chemically-stained sediments supported vent-endemic fauna including the Pompeii worm (Alvinella pompejana) and other polychaete worms, along with pycnogonids, rat-tail fish, and galatheid crabs. This discovery provided the first evidence that the eastern segment of the GSC may have contained high-temperature, black smoker vents.

Jurassic Diabase from Leesburg, VA: A Proposed Lunar Simulant

NASA Technical Reports Server (NTRS)

Taylor, Patrick T.; Lowman, P. D.; Nagihara, Seiichi; Milam, M. B.; Nakamura, Yosio

2008-01-01

A study of future lunar seismology and heat flow is being carried out as part of the NASA Lunar Sortie Science Program. This study will include new lunar drilling techniques, using a regolith simulant, for emplacement of instruments. Previous lunar simulants, such as JSC-1 and MLS-1, were not available when the study began, so a local simulant source was required. Diabase from a quarry at Leeseburg, Virginia, was obtained from the Luck Stone Corporation. We report here initial results of a petrographic examination of this rock, GSC-1 henceforth.

Jurassic Diabase from Leesburg, VA: A Proposed Lunar Simulant

NASA Technical Reports Server (NTRS)

Taylor, P. T.; Lowman, P. D.; Nagihara, Seiichi; Milam, M. B.; Nakamura, Yosio

2008-01-01

A study of future lunar seismology and heat flow is being carried out as part of the NASA Lunar Sortie Science Program [1].This study will include new lunar drilling techniques, using a regolith simulant, for emplacement of instruments. Previous lunar simulants, such as JSC-I and MLS-l, were not available when the study began, so a local simulant source was required. Diabase from a quarry at Leesburg, Virginia, was obtained from the Luck Stone Corporation. We report here initial results of a petrographic examination of this rock, GSC-1 henceforth.

New digital magnetic anomaly database for North America

USGS Publications Warehouse

Finn, C.A.; Pilkington, M.; Cuevas, A.; Hernandez, I.; Urrutia, J.

2001-01-01

The Geological Survey of Canada (GSC), U.S. Geological Survey (USGS), and Consejo de Recursos Minerales of Mexico (CRM) are compiling an upgraded digital magnetic anomaly database and map for North America. This trinational project is expected to be completed by late 2002.

EphA2 Promotes Infiltrative Invasion of Glioma Stem Cells in vivo through Crosstalk with Akt and Regulates Stem Properties

PubMed Central

Miao, Hui; Gale, Nickolas W.; Guo, Hong; Qian, Juan; Petty, Aaron; Kaspar, James; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George; Hambardzumyan, Dolores; Lathia, Justin D.; Rich, Jeremy N.; Lee, Jeongwu; Wang, Bingcheng

2014-01-01

Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma (GBM), but the underlying mechanisms remain incompletely understood. Using human glioblastoma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo. EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt-EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild type littermates. Mechanistically EphA2 knockdown suppressed stem properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem properties in a kinase-independent manner and increased Sox2 expression. In addition to suppressing invasion, disrupting Akt-EphA2 crosstalk attenuated stem marker expression and neurosphere formation while having minimal effects on tumorigenesis, suggesting that the Akt-EphA2 signaling axis contributes to the stem properties. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and contributes to the maintenance of stem properties. PMID:24488013

EphA2 promotes infiltrative invasion of glioma stem cells in vivo through cross-talk with Akt and regulates stem cell properties.

PubMed

Miao, H; Gale, N W; Guo, H; Qian, J; Petty, A; Kaspar, J; Murphy, A J; Valenzuela, D M; Yancopoulos, G; Hambardzumyan, D; Lathia, J D; Rich, J N; Lee, J; Wang, B

2015-01-29

Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma multiforme (GBM), but the underlying mechanisms remain incompletely understood. Using human glioma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo. EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt-EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild-type (WT) littermates. Mechanistically EphA2 knockdown suppressed stem cell properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem cell properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem cell properties in a kinase-independent manner and increased Sox2 expression. Disruption of Akt-EphA2 cross-talk attenuated stem cell marker expression and neurosphere formation while having minimal effects on tumorigenesis. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and regulates glioma stem cell properties.

Low-mass X-ray binary MAXI J1421-613 observed by MAXI GSC and Swift XRT

NASA Astrophysics Data System (ADS)

Serino, Motoko; Shidatsu, Megumi; Ueda, Yoshihiro; Matsuoka, Masaru; Negoro, Hitoshi; Yamaoka, Kazutaka; Kennea, Jamie A.; Fukushima, Kosuke; Nagayama, Takahiro

2015-04-01

Monitor of All sky X-ray Image (MAXI) discovered a new outburst of an X-ray transient source named MAXI J1421-613. Because of the detection of three X-ray bursts from the source, it was identified as a neutron star low-mass X-ray binary. The results of data analyses of the MAXI GSC (Gas Slit Camera) and the Swift XRT (X-Ray Telescope) follow-up observations suggest that the spectral hardness remained unchanged during the first two weeks of the outburst. All the XRT spectra in the 0.5-10 keV band can be well explained by thermal Comptonization of multi-color disk blackbody emission. The photon index of the Comptonized component is ≈ 2, which is typical of low-mass X-ray binaries in the low/hard state. Since X-ray bursts have a maximum peak luminosity, it is possible to estimate the (maximum) distance from its observed peak flux. The peak flux of the second X-ray burst, which was observed by the GSC, is about 5 photons cm-2 s-1. By assuming a blackbody spectrum of 2.5 keV, the maximum distance to the source is estimated as 7 kpc. The position of this source is contained by the large error regions of two bright X-ray sources detected with Orbiting Solar Observatory-7 (OSO-7) in the 1970s. Besides this, no past activities at the XRT position are reported in the literature. If MAXI J1421-613 is the same source as (one of) these, the outburst observed with MAXI may have occurred after a quiescence of 30-40 years.

Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models

PubMed Central

Piao, Yuji; Park, Soon Young; Henry, Verlene; Smith, Bryan D.; Tiao, Ningyi; Flynn, Daniel L.

2016-01-01

Background Glioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy. Methods We investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone. Results In vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone. Conclusions Together, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma. PMID:26965451

A switch in the mode of Wnt signaling orchestrates the formation of germline stem cell differentiation niche in Drosophila

PubMed Central

Upadhyay, Maitreyi; Kuna, Michael; Tudor, Sara; Martino Cortez, Yesenia

2018-01-01

Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development. We find that the downstream non-canonical components, RhoA, Rac1 and cdc42, are expressed at high levels and are active in escort cell precursors of the female larval gonad compared to the adult somatic niche. Consistent with this expression pattern, we find that the non-canonical pathway components function in the larval stages but not in adults to regulate GSC differentiation. In the larval gonad, dWnt4, RhoA, Rac1 and cdc42 are required to promote intermingling of escort cell precursors, a function that then promotes proper escort cell function in the adults. We find that dWnt4 acts by modulating the activity of RhoA, Rac1 and cdc42, but not their protein levels. Together, our results indicate that at different points of development, dWnt4 switches from using the non-canonical pathway components to using a β-catenin-dependent canonical pathway in the escort cells to facilitate the proper differentiation of GSCs. PMID:29370168

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

PubMed Central

Domenis, Rossana; Cesselli, Daniela; Toffoletto, Barbara; Bourkoula, Evgenia; Caponnetto, Federica; Manini, Ivana; Beltrami, Antonio Paolo; Ius, Tamara; Skrap, Miran; Di Loreto, Carla

2017-01-01

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression. PMID:28107450

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells.

PubMed

Domenis, Rossana; Cesselli, Daniela; Toffoletto, Barbara; Bourkoula, Evgenia; Caponnetto, Federica; Manini, Ivana; Beltrami, Antonio Paolo; Ius, Tamara; Skrap, Miran; Di Loreto, Carla; Gri, Giorgia

2017-01-01

A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression.

Divergent evolution of temozolomide resistance in glioblastoma stem cells is reflected in extracellular vesicles and coupled with radiosensitization.

PubMed

Garnier, Delphine; Meehan, Brian; Kislinger, Thomas; Daniel, Paul; Sinha, Ankit; Abdulkarim, Bassam; Nakano, Ichiro; Rak, Janusz

2018-01-22

Glioblastoma (GBM) is almost invariably fatal due to failure of standard therapy. The relapse of GBM following surgery, radiation, and systemic temozolomide (TMZ) is attributed to the ability of glioma stem cells (GSCs) to survive, evolve, and repopulate the tumor mass, events on which therapy exerts a poorly understood influence. Here we explore the molecular and cellular evolution of TMZ resistance as it emerges in vivo (xenograft models) in a series of human GSCs with either proneural (PN) or mesenchymal (MES) molecular characteristics. We observed that the initial response of GSC-initiated intracranial xenografts to TMZ is eventually replaced by refractory growth pattern. Individual tumors derived from the same isogenic GSC line expressed divergent and complex profiles of TMZ resistance markers, with a minor representation of O6-methylguanine DNA methyltransferase (MGMT) upregulation. In several independent TMZ-resistant tumors originating from MES GSCs we observed a consistent diminution of mesenchymal features, which persisted in cell culture and correlated with increased expression of Nestin, decline in transglutaminase 2 and sensitivity to radiation. The corresponding mRNA expression profiles reflective of TMZ resistance and stem cell phenotype were recapitulated in the transcriptome of exosome-like extracellular vesicles (EVs) released by GSCs into the culture medium. Intrinsic changes in the tumor-initiating cell compartment may include loss of subtype characteristics and reciprocal alterations in sensitivity to chemo- and radiation therapy. These observations suggest that exploiting therapy-induced changes in the GSC phenotype and alternating cycles of therapy may be explored to improve GBM outcomes. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Analysis of cataclysmic variable GSC02197-00886 evolution

NASA Astrophysics Data System (ADS)

Mitrofanova, A. A.; Borisov, N. V.; Shimansky, V. V.

2014-01-01

We present the spectral analysis of the physical state and evolution of the WZSge-type cataclysmic variable GSC02197-00886. The spectra of the system, covering the total orbital period at the time of the outburst on May 8, 2010, at the late relaxation stage, and in the quiescent state, were obtained at the SAO RAS 6-m BTA telescope in 2010-2012. From the absorption and emission HI, He I, and Fe II lines, we have determined the radial velocities for all the nights of observations and constructed the maps of Doppler tomography for the quiescent state. It was found that during the outburst the spectra of the object were formed in an optically thick accretion disk with an effective temperature of T eff ≈ 45 000 K and in a hotter boundary layer. During the relaxation of the system, the accretion disk gradually became optically thinner in the continuum and in the emission lines. In the quiescent state (July 2012), the continuous spectrum was dominated by the radiation of the cooling white dwarf with T eff = 18 000 K. The emission lines are formed on the surface of the cool star by the X-ray irradiation of the 1RXSJ213807.1+261958 source. We propose a method for determining the parameters of the white dwarf, based on the numerical modeling of the system spectra in the quiescent state and their comparison with the observed spectra. It is shown that the effective temperature of white dwarf has decreased by Δ T eff = 6000 K during the relaxation from August 2010 to July 2012. We have obtained a set of parameters for GSC02197-00886 and shown their good agreement with the average parameters of the W Z Sge-type systems, presented in the literature.

Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.

PubMed

Faria E Souza, Belmira S; Carvalho, Helison O; Taglialegna, Talisson; Barros, Albenise Santana A; da Cunha, Edilson Leal; Ferreira, Irlon Maciel; Keita, Hady; Navarrete, Andres; Carvalho, José Carlos Tavares

2017-09-01

Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.

UDE-based control of variable-speed wind turbine systems

NASA Astrophysics Data System (ADS)

Ren, Beibei; Wang, Yeqin; Zhong, Qing-Chang

2017-01-01

In this paper, the control of a PMSG (permanent magnet synchronous generator)-based variable-speed wind turbine system with a back-to-back converter is considered. The uncertainty and disturbance estimator (UDE)-based control approach is applied to the regulation of the DC-link voltage and the control of the RSC (rotor-side converter) and the GSC (grid-side converter). For the rotor-side controller, the UDE-based vector control is developed for the RSC with PMSG control to facilitate the application of the MPPT (maximum power point tracking) algorithm for the maximum wind energy capture. For the grid-side controller, the UDE-based vector control is developed to control the GSC with the power reference generated by a UDE-based DC-link voltage controller. Compared with the conventional vector control, the UDE-based vector control can achieve reliable current decoupling control with fast response. Moreover, the UDE-based DC-link voltage regulation can achieve stable DC-link voltage under model uncertainties and external disturbances, e.g. wind speed variations. The effectiveness of the proposed UDE-based control approach is demonstrated through extensive simulation studies in the presence of coupled dynamics, model uncertainties and external disturbances under varying wind speeds. The UDE-based control is able to generate more energy, e.g. by 5% for the wind profile tested.

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

Radchenko, Valery; Engle, Jonathan Ward; Medvedev, Dmitri G.

Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/ 44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti inmore » week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 10 2–10 3. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In conclusion, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥10 6.« less

GSC configuration management plan

NASA Technical Reports Server (NTRS)

Withers, B. Edward

1990-01-01

The tools and methods used for the configuration management of the artifacts (including software and documentation) associated with the Guidance and Control Software (GCS) project are described. The GCS project is part of a software error studies research program. Three implementations of GCS are being produced in order to study the fundamental characteristics of the software failure process. The Code Management System (CMS) is used to track and retrieve versions of the documentation and software. Application of the CMS for this project is described and the numbering scheme is delineated for the versions of the project artifacts.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

PubMed Central

Carén, Helena; Stricker, Stefan H.; Bulstrode, Harry; Gagrica, Sladjana; Johnstone, Ewan; Bartlett, Thomas E.; Feber, Andrew; Wilson, Gareth; Teschendorff, Andrew E.; Bertone, Paul; Beck, Stephan; Pollard, Steven M.

2015-01-01

Summary Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM. PMID:26607953

Nanotubes mediate niche-stem cell signaling in the Drosophila testis

PubMed Central

Inaba, Mayu; Buszczak, Michael; Yamashita, Yukiko M.

2015-01-01

Stem cell niches provide resident stem cells with signals that specify their identity. Niche signals act over a short-range such that only stem cells but not their differentiating progeny receive the self-renewing signals1. However, the cellular mechanisms that limit niche signaling to stem cells remain poorly understood. Here we show that the Drosophila male germline stem cells (GSCs) form previously unrecognized structures, microtubule-based (MT)-nanotubes, which extend into the hub, a major niche component. MT-nanotubes are observed specifically within GSC populations, and require IFT (intraflagellar transport) proteins for their formation. The BMP receptor Tkv localizes to MT-nanotubes. Perturbation of MT-nanotubes compromises activation of Dpp signaling within GSCs, leading to GSC loss. Moreover, Dpp ligand and Tkv receptor interaction is necessary and sufficient for MT-nanotube formation. We propose that MT-nanotubes provide a novel mechanism for selective receptor-ligand interaction, contributing to the short-range nature of niche-stem cell signaling. PMID:26131929

ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.

PubMed

Bassoy, Esen Yonca; Kasahara, Atsuko; Chiusolo, Valentina; Jacquemin, Guillaume; Boydell, Emma; Zamorano, Sebastian; Riccadonna, Cristina; Pellegatta, Serena; Hulo, Nicolas; Dutoit, Valérie; Derouazi, Madiha; Dietrich, Pierre Yves; Walker, Paul R; Martinvalet, Denis

2017-06-01

Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. © 2017 The Authors.

Monitoring Wind Turbine Loading Using Power Converter Signals

NASA Astrophysics Data System (ADS)

Rieg, C. A.; Smith, C. J.; Crabtree, C. J.

2016-09-01

The ability to detect faults and predict loads on a wind turbine drivetrain's mechanical components cost-effectively is critical to making the cost of wind energy competitive. In order to investigate whether this is possible using the readily available power converter current signals, an existing permanent magnet synchronous generator based wind energy conversion system computer model was modified to include a grid-side converter (GSC) for an improved converter model and a gearbox. The GSC maintains a constant DC link voltage via vector control. The gearbox was modelled as a 3-mass model to allow faults to be included. Gusts and gearbox faults were introduced to investigate the ability of the machine side converter (MSC) current (I q) to detect and quantify loads on the mechanical components. In this model, gearbox faults were not detectable in the I q signal due to shaft stiffness and damping interaction. However, a model that predicts the load change on mechanical wind turbine components using I q was developed and verified using synthetic and real wind data.

Problem-Solving Under Time Constraints: Alternatives for the Commander’s Estimate

DTIC Science & Technology

1990-03-26

CHOOL OF ADVANCED MILITAR (If applicable) STUDIES, USAC&GSC IATZL-SWV 6. ADDRESS (City, State, and ZIP Code ) 7b. ADDRESS (City, State, and ZIP Code ...NOTATION 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP DECISIONJ*MAKING...OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code ) 122c. OFFICE SYMBOL MAJ TIMOTHY D. LYNCH 9 684-3437 1 AT71-.qWV DO Form 1473, JUN 86

The First Precision CCD Observations of the Near Contact Binary, UY Muscae

NASA Astrophysics Data System (ADS)

McKenzie, R.; Stoddard, M. L.; Samec, R. G.; Faulkner, D. R.

2003-05-01

As a part of our study of solar type stars with gas streams we observed UY Muscae [Star "y" (Oosterhoff, BAIN #148, 1928) GSC 8987 392, α (2000) = 12h 30m 47s , δ (2000) = -66° 01' 52.8"]. The observations were taken at CTIO in Chili with the 0.9-m reflector on 18, 19, 20, 23 May 2001, by RGS and DRF. The CFIM T2K CCD camera with standard UBVRcIc filters in quad mode were used. More than 200 observations were taken in each pass band. The stars (GSC 8987 1279 α (2000) = 12h30m43.7s, δ (2000) = -65°59 '45") and (GSC 8987 1884, α (2000) = 12h30m45.7s, δ (2000) = -66°01 '5") were used as comparison and check stars, respectively. Two mean epochs of minimum light were determined from primary and secondary eclipses, HJD = 2452047.6239(0.0017) and 2452049.5918(0.0005) . Standard errors are given in parentheses. We calculated the following ephemeris from our data: HJD Tmin I = 2452047.6240(0.0003) + 0.562273(0.000151)d*E . A UBVRI synthetic light curve solution was calculated using the Wilson Code. It indicates the primary (more massive) component is under-filling its Roche lobe [fill-out = 94.4(0.001) critical lobe. This is similar to an Algol system. The final parameters include a mass ratio, m2/m1 = 0.551(0.001) , and a temperature difference T1-T2 = 1280(3)K. Two spots were modeled: a stream spot with a temperature factor of 1.060(0.002) very near the L1 point of the primary component and a solar type dark spot of radius 25.2(0.3)° with a T factor of 0.970( 0.001). Large night to night variations in the light curve lead us to believe that the components are saturated with magnetic activity. It is possible that the system was previously in contact and is undergoing TRO oscillations. Our model indicates that the components are currently separating. Further results of this study will be presented. We wish to thank CTIO for their allocation of observing time, and a small research grant from the American Astronomical Society which supported this run.

Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients

PubMed Central

Yang, Shuai; Tso, Jonathan L.; Menjivar, Jimmy C.; Wei, Bowen; Lucey, Gregory M.; Mareninov, Sergey; Chen, Zugen; Liau, Linda M.; Lai, Albert; Nelson, Stanley F.; Cloughesy, Timothy F.; Tso, Cho-Lea

2015-01-01

Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11: Hazard Ratio (HR) = 11.5, p<0.001; RPS20: HR = 4.5, p = 0.03; RPS11+RPS20: HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11: HR = 1.19, p = 0.06; RPS20: HR = 1.25, p = 0.02; RPS11+RPS20: HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers. PMID:26506620

Morphology and segmentation of the western Galápagos Spreading Center, 90.5°-98°W: Plume-ridge interaction at an intermediate spreading ridge

NASA Astrophysics Data System (ADS)

Sinton, John; Detrick, Robert; Canales, J. Pablo; Ito, Garrett; Behn, Mark

2003-12-01

Complete multibeam bathymetric coverage of the western Galápagos Spreading Center (GSC) between 90.5°W and 98°W reveals the fine-scale morphology, segmentation and influence of the Galápagos hot spot on this intermediate spreading ridge. The western GSC comprises three morphologically defined provinces: A Western Province, located farthest from the Galápagos hot spot west of 95°30'W, is characterized by an axial deep, rift valley morphology with individual, overlapping, E-W striking segments separated by non-transform offsets; A Middle Province, between the propagating rift tips at 93°15'W and 95°30'W, with transitional axial morphology strikes ˜276°; An Eastern Province, closest to the Galápagos hot spot between the ˜90°50'W Galápagos Transform and 93°15'W, with an axial high morphology generally less than 1800 m deep, strikes ˜280°. At a finer scale, the axial region consists of 32 individual segments defined on the basis of smaller, mainly <2 km, offsets. These offsets mainly step left in the Western and Middle Provinces, and right in the Eastern Province. Glass compositions indicate that the GSC is segmented magmatically into 8 broad regions, with Mg # generally decreasing to the west within each region. Striking differences in bathymetric and lava fractionation patterns between the propagating rifts with tips at 93°15'W and 95°30'W reflect lower overall magma supply and larger offset distance at the latter. The structure of the Eastern Province is complicated by the intersection of a series of volcanic lineaments that appear to radiate away from a point located on the northern edge of the Galápagos platform, close to the southern limit of the Galápagos Fracture Zone. Where these lineaments intersect the GSC, the ridge axis is displaced to the south through a series of overlapping spreading centers (OSCs); abandoned OSC limbs lie even farther south. We propose that southward displacement of the axis is promoted during intermittent times of increased plume activity, when lithospheric zones of weakness become volcanically active. Following cessation of the increased plume activity, the axis straightens by decapitating southernmost OSC limbs during short-lived propagation events. This process contributes to the number of right stepping offsets in the Eastern Province.

Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types.

PubMed

Cornish, Alex J; Filippis, Ioannis; David, Alessia; Sternberg, Michael J E

2015-09-01

Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. In this study, we integrate protein-protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. The GSC method successfully identifies known disease-cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine.

Intelligence Architecture, Echelons Corps and Below (ECB): Some Near Term Alternatives

DTIC Science & Technology

1991-04-05

intelligence missions. - Failure to have an annual "MI Table VIII" type evaluation system keeps MI units in the business of supporting other Table...Division) CAC: Combined Arms Center (Ft Leavenworth) CEWI: Combat Electronic Warfare Inteligence C&GSC: Command and General Staff College CI

CDinFusion – Submission-Ready, On-Line Integration of Sequence and Contextual Data

PubMed Central

Hankeln, Wolfgang; Wendel, Norma Johanna; Gerken, Jan; Waldmann, Jost; Buttigieg, Pier Luigi; Kostadinov, Ivaylo; Kottmann, Renzo; Yilmaz, Pelin; Glöckner, Frank Oliver

2011-01-01

State of the art (DNA) sequencing methods applied in “Omics” studies grant insight into the ‘blueprints’ of organisms from all domains of life. Sequencing is carried out around the globe and the data is submitted to the public repositories of the International Nucleotide Sequence Database Collaboration. However, the context in which these studies are conducted often gets lost, because experimental data, as well as information about the environment are rarely submitted along with the sequence data. If these contextual or metadata are missing, key opportunities of comparison and analysis across studies and habitats are hampered or even impossible. To address this problem, the Genomic Standards Consortium (GSC) promotes checklists and standards to better describe our sequence data collection and to promote the capturing, exchange and integration of sequence data with contextual data. In a recent community effort the GSC has developed a series of recommendations for contextual data that should be submitted along with sequence data. To support the scientific community to significantly enhance the quality and quantity of contextual data in the public sequence data repositories, specialized software tools are needed. In this work we present CDinFusion, a web-based tool to integrate contextual and sequence data in (Multi)FASTA format prior to submission. The tool is open source and available under the Lesser GNU Public License 3. A public installation is hosted and maintained at the Max Planck Institute for Marine Microbiology at http://www.megx.net/cdinfusion. The tool may also be installed locally using the open source code available at http://code.google.com/p/cdinfusion. PMID:21935468

Overexpression of leptin receptor in human glioblastoma: Correlation with vasculogenic mimicry and poor prognosis

PubMed Central

Yue, Zhijian; Zhang, Yuhui; Wang, Laixing; Liu, Jianmin

2017-01-01

Vasculogenic mimicry (VM) was an important tumor blood supply to complement the endothelial cell-dependent angiogenesis, while leptin and receptor (ObR) involved in angiogenesis in glioblastoma has been reported on previous study, but the relationship between ObR expression and VM formation in human glioblastoma tissues, as well as their prognostic significance still remains unclear. In our study, we found that VM recognized by CD31-/PAS+ immunohistochemical staining in glioblastoma tissues showed a positive correlation with leptin expression (r = 0.58, P < 0.01), as well as ObR expression in glioblastoma tissues (r = 0.61, P < 0.01). Association of glial to mesenchymal transition (GMT)-related molecular with ObR expression and VM formation in glioblastoma tissues indicated that ObR-positive glioblastoma cells with GMT phenotype might be more likely to constitute VM, and co-expression of ObR and CD133 or Nestin to constitute the channel impliated that ObR-positive glioblastoma cells displayed glioblastoma stem cells (GSC) properties. Moreover, Kaplan–Meier statistical analysis showed that patients with more VM or ObR expression displayed poorer prognosis for overall survival times than patients with less expression (VMhigh vs. VMlow: P = 0.033; ObRhigh vs. ObRlow: P = 0.009). And ObR+ glioblastoma cells with GSC characteristic were mostly involved in VM formation, whereas a little part of cells were also related to microvascular density (MVD), which suggested that ObR was an important target for anticancer therapy, so further related studies were needed to improve glioblastoma treatment. PMID:28938545

Monitoring in real time the effect of TLX overexpression on proliferation and migration of C6 cells.

PubMed

Li, G L; Fang, S H; Xu, B

2017-01-01

Orphan nuclear receptor TLX has been shown to play an essential role in regulating the self-renewal and proliferation of neural stem cells (NSCs). However, TLX overexpression in NSCs induces long-term NSC expansion and further leads to glioma initiation in mouse when combined with p53 mutations. Whether overexpression of TLX plays a role in glioma stem cell (GSC) proliferation and migration still remains largely unknown. In this study, we infected C6 cells, a special glioma cell line which is mainly composed of cancer stem cells(CSCs), with lentiviruses expressing GFP(LV-GFP) or GFP-T2A-TLX(LV-TLX) and then monitored cell proliferation and migration using the real-time analyzer system (RTCA, xCELLigence, Roche). We found that the cell index (CI) observed for the TLX overexpressing C6 cells showed a lower value than that of the LV-GFP transduced cells. And the MTT results correlated highly with the RTCA proliferation assessments. Furthermore, the expression of p21 was decreased while other downstream genes PTEN and p53 were not significantly changed in TLX overexpressing C6 cells . These findings strongly indicate that TLX overexpression has the ability to decrease the proliferating and migratory properties of C6 cells by targeting p21. Further, our results suggest that TLX overexpression may also have a similar inhibitory effect on GSC proliferation and migration.

Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/ 44Sc generator development

DOE PAGES

Radchenko, Valery; Engle, Jonathan Ward; Medvedev, Dmitri G.; ...

2017-04-07

Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/ 44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti inmore » week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 10 2–10 3. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In conclusion, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥10 6.« less

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

[Interpretation on Chinese surgeons' consensus opinion for the definition of gastric stump cancer (version 2018)].

PubMed

Gao, Zhidong; Jiang, Kewei; Ye, Yingjiang; Wang, Shan

2018-05-25

Gastric stump cancer(GSC) is defined as newly developed remnant stomach cancer following gastrectomy. This definition initially referred to carcinoma detected in the remnant stomach more than 5 years after the primary surgery for a benign disease. Subsequently, this timeframe was extended to 10 years after the primary surgery for a malignant disease. Recently, the concept of "carcinoma in the remnant stomach(CRS)" proposed by the Japanese Gastric Cancer Association was introduced in China. The new definition encompasses all carcinomas arising in the remnant stomach following gastrectomy, irrespective of the histology of the primary lesion, extent of resection, or reconstruction method. It includes all carcinoma types that have developed in the remnant stomach, such as newly developed cancer, recurrent cancer, remaining cancer, and multiple cancers. Considering the current diagnosis and treatment status of gastric cancer in China, if CRS is to be used as a direct equivalent to GSC in clinical practice, confusion may arise concerning disease identification and diagnosis. Following several discussion rounds, a meta-analysis of the literatures at home and abroad, and a multicenter national retrospective study with a large sample population, the "Chinese surgeons' consensus opinion for the definition of gastric stump cancer (version 2018)" was completed. By reviewing the detailed evidence-based medicine supporting the consensus document, this paper aims to assist clinical diagnosis and enhance future academic exchange.

Live-Cell Imaging of the Adult Drosophila Ovary Using Confocal Microscopy.

PubMed

Shalaby, Nevine A; Buszczak, Michael

2017-01-01

The Drosophila ovary represents a key in vivo model used to study germline stem cell (GSC) maintenance and stem cell daughter differentiation because these cells and their somatic cell neighbors can be identified at single-cell resolution within their native environment. Here we describe a fluorescent-based technique for the acquisition of 4D datasets of the Drosophila ovariole for periods that can exceed 12 consecutive hours. Live-cell imaging facilitates the investigation of molecular and cellular dynamics that were not previously possible using still images.

Module Cluster: TTP-003.00 (GSC) Modifying Academic Behavior.

ERIC Educational Resources Information Center

Brent, George

The purpose of this module cluster is to enable students to demonstrate that they can plan for changes in the academic behavior of their elementary school pupils and then change the behavior. The cluster is intended for use after the completion of normal college entrance competencies, liberal arts requirements, practicum experience, methods…

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

USDA-ARS?s Scientific Manuscript database

We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the minimum information about any (x) sequence (MIxS). The standards are the minimum information about a single amplified genome (MISAG) and the ...

Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

NASA Astrophysics Data System (ADS)

Heffernan, John M.; Sirianni, Rachael W.

2018-02-01

Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

Amount of gas hydrate estimated from compressional- and shear-wave velocities at the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well

USGS Publications Warehouse

Lee, M.W.

1999-01-01

The amount of in situ gas hydrate concentrated in the sediment pore space at the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well was estimated by using compressional-wave (P-wave) and shear-wave (S-wave) downhole log measurements. A weighted equation developed for relating the amount of gas hydrate concentrated in the pore space of unconsolidated sediments to the increase of seismic velocities was applied to the acoustic logs with porosities derived from the formation density log. A weight of 1.56 (W=1.56) and the exponent of 1 (n=1) provided consistent estimates of gas hydrate concentration from the S-wave and the P-wave logs. Gas hydrate concentration is as much as 80% in the pore spaces, and the average gas hydrate concentration within the gas-hydrate-bearing section from 897 m to 1110 m (excluding zones where there is no gas hydrate) was calculated at 39.0% when using P-wave data and 37.8% when using S-wave data.

Gas composition and isotopic geochemistry of cuttings, core, and gas hydrate from the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well

USGS Publications Warehouse

Lorenson, T.D.

1999-01-01

Molecular and isotopic composition of gases from the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well demonstrate that the in situ gases can be divided into three zones composed of mixtures of microbial and thermogenic gases. Sediments penetrated by the well are thermally immature; thus the sediments are probably not a source of thermogenic gas. Thermogenic gas likely migrated from depths below 5000 m. Higher concentrations of gas within and beneath the gas hydrate zone suggest that gas hydrate is a partial barrier to gas migration. Gas hydrate accumulations occur wholly within zone 3, below the base of permafrost. The gas in gas hydrate resembles, in part, the thermogenic gas in surrounding sediments and gas desorbed from lignite. Gas hydrate composition implies that the primary gas hydrate form is Structure I. However, Structure II stabilizing gases are more concentrated and isotopically partitioned in gas hydrate relative to the sediment hosting the gas hydrate, implying that Structure II gas hydrate may be present in small quantities.

Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme

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

Huang, Shi-Xiong; Zhao, Zhong-Yan; Weng, Guo-Hu

Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expressionmore » of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3’-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients. - Highlights: • MiR-181a suppressed GSC formation and GBM tumorigenesis by targeting Notch2. • Notch2 and miR-181a expression were correlated with OS for GBM patients. • Notch2 and miR-181a have potential prognostic value in GBM patients.« less

Rejecting Astrophysical False Positives from the TrES Transiting Planet Survey: The Example of GSC 03885-00829

NASA Astrophysics Data System (ADS)

O'Donovan, Francis T.; Charbonneau, David; Torres, Guillermo; Mandushev, Georgi; Dunham, Edward W.; Latham, David W.; Alonso, Roi; Brown, Timothy M.; Esquerdo, Gilbert A.; Everett, Mark E.; Creevey, Orlagh L.

2006-06-01

Ground-based wide-field surveys for nearby transiting gas giants are yielding far fewer true planets than astrophysical false positives, some of which are difficult to reject. Recent experience has highlighted the need for careful analysis to eliminate astronomical systems in which light from a faint eclipsing binary is blended with that from a bright star. During the course of the Transatlantic Exoplanet Survey, we identified a system presenting a transit-like periodic signal. We obtained the proper motion and infrared color of this target (GSC 03885-00829) from publicly available catalogs, which suggested this star is an F dwarf, supporting our transit hypothesis. This spectral classification was confirmed using spectroscopic observations from which we determined the stellar radial velocity. The star did not exhibit any signs of a stellar mass companion. However, subsequent multicolor photometry displayed a color-dependent transit depth, indicating that a blend was the likely source of the eclipse. We successfully modeled our initial photometric observations of GSC 03885-00829 as the light from a K dwarf binary system superimposed on the light from a late F dwarf star. High-dispersion spectroscopy confirmed the presence of light from a cool stellar photosphere in the spectrum of this system. With this candidate, we demonstrate both the difficulty in identifying certain types of false positives in a list of candidate transiting planets and our procedure for rejecting these imposters, which may be useful to other groups performing wide-field transit surveys. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates.

PubMed

Vidak, Marko; Jovcevska, Ivana; Samec, Neja; Zottel, Alja; Liovic, Mirjana; Rozman, Damjana; Dzeroski, Saso; Juvan, Peter; Komel, Radovan

2018-05-04

Glioblastoma (GB) is the most aggressive brain malignancy. Although some potential glioblastoma biomarkers have already been identified, there is a lack of cell membrane-bound biomarkers capable of distinguishing brain tissue from glioblastoma and/or glioblastoma stem cells (GSC), which are responsible for the rapid post-operative tumor reoccurrence. In order to find new GB/GSC marker candidates that would be cell surface proteins (CSP), we have performed meta-analysis of genome-scale mRNA expression data from three data repositories (GEO, ArrayExpress and GLIOMASdb). The search yielded ten appropriate datasets, and three (GSE4290/GDS1962, GSE23806/GDS3885, and GLIOMASdb) were used for selection of new GB/GSC marker candidates, while the other seven (GSE4412/GDS1975, GSE4412/GDS1976, E-GEOD-52009, E-GEOD-68848, E-GEOD-16011, E-GEOD-4536, and E-GEOD-74571) were used for bioinformatic validation. The selection identified four new CSP-encoding candidate genes— CD276 , FREM2 , SPRY1 , and SLC47A1 —and the bioinformatic validation confirmed these findings. A review of the literature revealed that CD276 is not a novel candidate, while SLC47A1 had lower validation test scores than the other new candidates and was therefore not considered for experimental validation. This validation revealed that the expression of FREM2—but not SPRY1—is higher in glioblastoma cell lines when compared to non-malignant astrocytes. In addition, FREM2 gene and protein expression levels are higher in GB stem-like cell lines than in conventional glioblastoma cell lines. FREM2 is thus proposed as a novel GB biomarker and a putative biomarker of glioblastoma stem cells. Both FREM2 and SPRY1 are expressed on the surface of the GB cells, while SPRY1 alone was found overexpressed in the cytosol of non-malignant astrocytes.

Towards a standards-compliant genomic and metagenomic publication record

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

Fenner, Marsha W; Garrity, George M.; Field, Dawn

2008-04-01

Increasingly we are aware as a community of the growing need to manage the avalanche of genomic and metagenomic data, in addition to related data types like ribosomal RNA and barcode sequences, in a way that tightly integrates contextual data with traditional literature in a machine-readable way. It is for this reason that the Genomic Standards Consortium (GSC) formed in 2005. Here we suggest that we move beyond the development of standards and tackle standards-compliance and improved data capture at the level of the scientific publication. We are supported in this goal by the fact that the scientific community ismore » in the midst of a publishing revolution. This revolution is marked by a growing shift away from a traditional dichotomy between 'journal articles' and 'database entries' and an increasing adoption of hybrid models of collecting and disseminating scientific information. With respect to genomes and metagenomes and related data types, we feel the scientific community would be best served by the immediate launch of a central repository of short, highly structured 'Genome Notes' that must be standards-compliant. This could be done in the context of an existing journal, but we also suggest the more radical solution of launching a new journal. Such a journal could be designed to cater to a wide range of standards-related content types that are not currently centralized in the published literature. It could also support the demand for centralizing aspects of the 'gray literature' (documents developed by institutions or communities) such as the call by the GSCl for a central repository of Standard Operating Procedures describing the genomic annotation pipelines of the major sequencing centers. We argue that such an 'eJournal', published under the Open Access paradigm by the GSC, could be an attractive publishing forum for a broader range of standardization initiatives within, and beyond, the GSC and thereby fill an unoccupied yet increasingly important niche within the current research landscape.« less

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.

HAT-P-32b AND HAT-P-33b: TWO HIGHLY INFLATED HOT JUPITERS TRANSITING HIGH-JITTER STARS

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

Hartman, J. D.; Bakos, G. A.; Torres, G.

2011-11-20

We report the discovery of two exoplanets transiting high-jitter stars. HAT-P-32b orbits the bright V = 11.289 late-F-early-G dwarf star GSC 3281-00800, with a period P = 2.150008 {+-} 0.000001 d. The stellar and planetary masses and radii depend on the eccentricity of the system, which is poorly constrained due to the high-velocity jitter ({approx}80 m s{sup -1}). Assuming a circular orbit, the star has a mass of 1.16 {+-} 0.04 M{sub Sun} and radius of 1.22 {+-} 0.02 R{sub Sun }, while the planet has a mass of 0.860 {+-} 0.164 M{sub J} and a radius of 1.789 {+-}more » 0.025 R{sub J}. The second planet, HAT-P-33b, orbits the bright V = 11.188 late-F dwarf star GSC 2461-00988, with a period P = 3.474474 {+-} 0.000001 d. As for HAT-P-32, the stellar and planetary masses and radii of HAT-P-33 depend on the eccentricity, which is poorly constrained due to the high jitter ({approx}50 m s{sup -1}). In this case, spectral line bisector spans (BSs) are significantly anti-correlated with the radial velocity residuals, and we are able to use this correlation to reduce the residual rms to {approx}35 m s{sup -1}. We find that the star has a mass of 1.38 {+-} 0.04 M{sub Sun} and a radius of 1.64 {+-} 0.03 R{sub Sun} while the planet has a mass of 0.762 {+-} 0.101 M{sub J} and a radius of 1.686 {+-} 0.045 R{sub J} for an assumed circular orbit. Due to the large BS variations exhibited by both stars we rely on detailed modeling of the photometric light curves to rule out blend scenarios. Both planets are among the largest radii transiting planets discovered to date.« less

Gastrulation and pre-gastrulation morphogenesis, inductions, and gene expression: similarities and dissimilarities between urodelean and anuran embryos.

PubMed

Kaneda, Teruo; Motoki, Jun-ya Doi

2012-09-01

Studies of meso-endoderm and neural induction and subsequent body plan formation have been analyzed using mainly amphibians as the experimental model. Xenopus is currently the predominant model, because it best enables molecular analysis of these induction processes. However, much of the embryological information on these inductions (e.g., those of the Spemann-Mangold organizer), and on the morphogenetic movements of inductively interacting tissues, derives from research on non-model amphibians, especially urodeles. Although the final body pattern is strongly conserved in vertebrates, and although many of the same developmental genes are expressed, it has become evident that there are individually diverse modes of morphogenesis and timing of developmental events. Whether or not this diversity represents essential differences in the early induction processes remains unclear. The aim of this review is to compare the gastrulation process, induction processes, and gene expressions between a urodele, mainly Cynops pyrrhogaster, and an anura, Xenopus laevis, thereby to clarify conserved and diversified aspects. Cynops gastrulation differs significantly from that of Xenopus in that specification of the regions of the Xenopus dorsal marginal zone (DMZ) are specified before the onset of gastrulation, as marked by blastopore formation, whereas the equivalent state of specification does not occur in Cynops until the middle of gastrulation. Detailed comparison of the germ layer structure and morphogenetic movements during the pre-gastrula and gastrula stages shows that the entire gastrulation process should be divided into two phases of notochord induction and neural induction. Cynops undergoes these processes sequentially after the onset of gastrulation, whereas Xenopus undergoes notochord induction during a series of pre-gastrulation movements, and its traditionally defined period of gastrulation only includes the neural induction phase. Comparing the structure, fate, function and state of commitment of each domain of the DMZ of Xenopus and Cynops has revealed that the true form of the Spemann-Mangold organizer is suprablastoporal gsc-expressing endoderm that has notochord-inducing activity. Gsc-expressing deep endoderm and/or superficial endoderm in Xenopus is involved in inducing notochord during pre-gastrulation morphogenesis, rather than both gsc- and bra-expressing tissues being induced at the same time. Copyright © 2012 Elsevier Inc. All rights reserved.

Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma

PubMed Central

Singh, Melissa M.; Johnson, Blake; Venkatarayan, Avinashnarayan; Flores, Elsa R.; Zhang, Jianping; Su, Xiaoping; Barton, Michelle; Lang, Frederick; Chandra, Joya

2015-01-01

Background Glioblastoma (GBM) is the most common and aggressive form of brain cancer. Our previous studies demonstrated that combined inhibition of HDAC and KDM1A increases apoptotic cell death in vitro. However, whether this combination also increases death of the glioma stem cell (GSC) population or has an effect in vivo is yet to be determined. Therefore, we evaluated the translational potential of combined HDAC and KDM1A inhibition on patient-derived GSCs and xenograft GBM mouse models. We also investigated the changes in transcriptional programing induced by the combination in an effort to understand the induced molecular mechanisms of GBM cell death. Methods Patient-derived GSCs were treated with the combination of vorinostat, a pan-HDAC inhibitor, and tranylcypromine, a KDM1A inhibitor, and viability was measured. To characterize transcriptional profiles associated with cell death, we used RNA-Seq and validated gene changes by RT-qPCR and protein expression via Western blot. Apoptosis was measured using DNA fragmentation assays. Orthotopic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis and to validate gene changes in vivo. Results The combination of vorinostat and tranylcypromine reduced GSC viability and displayed efficacy in the U87 xenograft model. Additionally, the combination led to changes in apoptosis-related genes, particularly TP53 and TP73 in vitro and in vivo. Conclusions These data support targeting HDACs and KDM1A in combination as a strategy for GBM and identifies TP53 and TP73 as being altered in response to treatment. PMID:25795306

Module Cluster: TTP-001.00 (GSC) Reinforcement Principles for Classroom Use.

ERIC Educational Resources Information Center

Brent, George

The purpose of this module cluster is to enable students to define the basic operant terms, to state the basic operant principles, to read operant measurement charts, and to use operant principles in elementary classrooms with both social and academic behaviors. It is intended for use by teacher education students with the cooperation of an…

Module Cluster: RTE-001.00 (GSC) Advanced Teaching of Reading.

ERIC Educational Resources Information Center

Brown, Estelle

Several module clusters were developed at Glassboro State College as the result of involvement in the Camden Teacher Corps project. The clusters are the primary mode of instruction in this competency-based teacher education program. Many of these modules are based on a list of teacher competencies developed by members of the Elementary Education…

The"minimum information about an environmental sequence" (MIENS) specification

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

Yilmaz, P.; Kottmann, R.; Field, D.

We present the Genomic Standards Consortium's (GSC) 'Minimum Information about an ENvironmental Sequence' (MIENS) standard for describing marker genes. Adoption of MIENS will enhance our ability to analyze natural genetic diversity across the Tree of Life as it is currently being documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.

Some first experiments on the photometric calibration of Schmidt plates against the Tycho catalogue

NASA Technical Reports Server (NTRS)

Morrison, J. E.; Lasker, B.; McLean, B.; Bucciarelli, B.; Spagna, A.; Zacchei, A.

1997-01-01

Preliminary work carried out with the aim of reducing the Guide Star Catalog (GSC2) measurements of the Palomar 2 plates with the Tycho catalog for a 625 sq deg test field centered on the North Galactic Pole, is reported on and the results are presented. The emphasis was on the photometric calibrations.

Assessing the short-term clock drift of early broadband stations with burst events of the 26 s persistent and localized microseism

NASA Astrophysics Data System (ADS)

Xie, J.; Ni, S.; Chu, R.; Xia, Y.

2017-12-01

Accurate seismometer clock plays an important role in seismological studies including earthquake location and tomography. However, some seismic stations may have clock drift larger than 1 second, especially in early days of global seismic network. The 26 s Persistent Localized (PL) microseism event in the Gulf of Guinea sometime excites strong and coherent signals, and can be used as repeating source for assessing stability of seismometer clocks. Taking station GSC/TS in southern California, USA as an example, the 26 s PL signal can be easily observed in the ambient Noise Cross-correlation Function (NCF) between GSC/TS and a remote station. The variation of travel-time of this 26 s signal in the NCF is used to infer clock error. A drastic clock error is detected during June, 1992. This short-term clock error is confirmed by both teleseismic and local earthquake records with a magnitude of ±25 s. Using 26 s PL source, the clock can be validated for historical records of sparsely distributed stations, where usual NCF of short period microseism (<20 s) might be less effective due to its attenuation over long interstation distances. However, this method suffers from cycling problem, and should be verified by teleseismic/local P waves. The location change of the 26 s PL source may influence the measured clock drift, using regional stations with stable clock, we estimate the possible location change of the source.

Investigating gas hydrate as a factor in accretionary margin frontal ridge slope failures and cold seep biogeochemistry

USGS Publications Warehouse

Enkin, R.; Esteban, L.; Haacke, R.; Hamilton, T.S.; Hogg, M.; Lapham, L.; Middleton, G.; Neelands, P.; Pohlman, John W.; Riedel, M; Rose, K.; Schlesinger, A.; Standen, G.; Stephenson, A.; Taylor, S.; Waite, W.; Wang, X.

2008-01-01

During August 2008, a research expedition (2008-007-PGC) was carried out offshore Vancouver Island on the northern Cascadia Margin (Figure 1) to study the role of gas hydrate in slope stability and cold seep biogeochemistry. The cruise was organized by the Geological Survey of Canada (GSC) as part of the Earth Science Sector, Natural Gas Hydrate Program, Natural Resources Canada (NRCan). This international collaboration included McGill University, University of Victoria, the U.S. Geological Survey, Florida State University, and the U.S. Department of Energy.

Biofeedback With Implanted Blood-Pressure Device

NASA Technical Reports Server (NTRS)

Rischell, Robert E.

1988-01-01

Additional uses found for equipment described in "Implanted Blood-Pressure-Measuring Device" (GSC-13042). Implanted with device electronic circuitry that measures, interprets, and transmits data via inductive link through patient's skin to external receiver. Receiver includes audible alarm generator activated when patient's blood pressure exceeds predetermined threshold. Also included in receiver a blood-pressure display, recorder, or both, for use by patient or physician.

Optical Observations of BQ Cam (V 0332+53) During Outburst

NASA Astrophysics Data System (ADS)

Ozbey Arabaci, Mehtap; Beklen, Elif; Donmez, Burcin; Shameoni Niaei, Mohammad

2016-10-01

Recent MAXI/GSC observations reported an X-ray brightening of the Be/X-ray system V 0332+53 (ATel #9596). Following this report, we performed optical spectroscopic and photometric observations of BQ Cam, identified as the optical counterpart of the system, with the 1.5 m Russian-Turkish telescope of TUBITAK National Observatory (Antalya, Turkey) on 2016 October 6 (MJD 57667).

MAXI/GSC detection of an undergoing soft-to-hard state transition of MAXI J1535-571

NASA Astrophysics Data System (ADS)

Negoro, H.; Sugawara, Y.; Nakajima, M.; Sakamaki, A.; Maruyama, W.; Mihara, T.; Nakahira, S.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Kawai, N.; Sugizaki, M.; Tachibana, Y.; Morita, K.; Sakamoto, T.; Serino, M.; Sugita, S.; Kawakubo, Y.; Hashimoto, T.; Yoshida, A.; Ueno, S.; Tomida, H.; Ishikawa, M.; Isobe, N.; Shimomukai, R.; Ueda, Y.; Tanimoto, A.; Morita, T.; Yamada, S.; Tsuboi, Y.; Iwakiri, W.; Sasaki, R.; Kawai, H.; Sato, T.; Tsunemi, H.; Yoneyama, T.; Yamauchi, M.; Hidaka, K.; Iwahori, S.; Kawamuro, T.; Yamaoka, K.; Shidatsu, M.

2018-06-01

We report an undergoing soft-to-hard state transition of the black hole candidate MAXI J1535-571 in outburst (ATel #10699). After the unexpectedly rapid decrease in the X-ray flux remaining in the soft state from 2018 April 16 (ATel #11568), the source underwent a hard state transition around April 30 (ATel #11611).

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

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

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

The number of genomes from uncultivated microbes will soon surpass the number of isolate genomes in public databases (Hugenholtz, Skarshewski, & Parks, 2016). Technological advancements in high-throughput sequencing and assembly, including single-cell genomics and the computational extraction of genomes from metagenomes (GFMs), are largely responsible. Here we propose community standards for reporting the Minimum Information about a Single-Cell Genome (MIxS-SCG) and Minimum Information about Genomes extracted From Metagenomes (MIxS-GFM) specific for Bacteria and Archaea. The standards have been developed in the context of the International Genomics Standards Consortium (GSC) community (Field et al., 2014) and can be viewed as amore » supplement to other GSC checklists including the Minimum Information about a Genome Sequence (MIGS), Minimum information about a Metagenomic Sequence(s) (MIMS) (Field et al., 2008) and Minimum Information about a Marker Gene Sequence (MIMARKS) (P. Yilmaz et al., 2011). Community-wide acceptance of MIxS-SCG and MIxS-GFM for Bacteria and Archaea will enable broad comparative analyses of genomes from the majority of taxa that remain uncultivated, improving our understanding of microbial function, ecology, and evolution.« less

Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity

PubMed Central

Kim, Youngmi; Kim, Eunhee; Wu, Qiulian; Guryanova, Olga; Hitomi, Masahiro; Lathia, Justin D.; Serwanski, David; Sloan, Andrew E.; Weil, Robert J.; Lee, Jeongwu; Nishiyama, Akiko; Bao, Shideng; Hjelmeland, Anita B.; Rich, Jeremy N.

2012-01-01

Growth factor-mediated proliferation and self-renewal maintain tissue-specific stem cells and are frequently dysregulated in cancers. Platelet-derived growth factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors, as proven in genetically engineered models. While PDGFRα alterations inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral GBM heterogeneity. We found that PDGFRα is expressed only in a subset of GBMs, while PDGFRβ is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or pharmacological targeting of PDGFRβ (but not PDGFRα) attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFRβ inhibition decreased activation of the cancer stem cell signaling node STAT3, while constitutively active STAT3 rescued the loss of GSC self-renewal caused by PDGFRβ targeting. In silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor. Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies. PMID:22661233

A role for post-transcriptional control of endoplasmic reticulum dynamics and function in C. elegans germline stem cell maintenance.

PubMed

Maheshwari, Richa; Pushpa, Kumari; Subramaniam, Kuppuswamy

2016-09-01

Membrane-bound receptors, which are crucial for mediating several key developmental signals, are synthesized on endoplasmic reticulum (ER). The functional integrity of ER must therefore be important for the regulation of at least some developmental programs. However, the developmental control of ER function is not well understood. Here, we identify the C. elegans protein FARL-11, an ortholog of the mammalian STRIPAK complex component STRIP1/2 (FAM40A/B), as an ER protein. In the C. elegans embryo, we find that FARL-11 is essential for the cell cycle-dependent morphological changes of ER and for embryonic viability. In the germline, FARL-11 is required for normal ER morphology and for membrane localization of the GLP-1/Notch receptor involved in germline stem cell (GSC) maintenance. Furthermore, we provide evidence that PUF-8, a key translational regulator in the germline, promotes the translation of farl-11 mRNA. These findings reveal that ER form and function in the C. elegans germline are post-transcriptionally regulated and essential for the niche-GSC signaling mediated by GLP-1. © 2016. Published by The Company of Biologists Ltd.

From stem cell to embryo without centrioles.

PubMed

Stevens, Naomi R; Raposo, Alexandre A S F; Basto, Renata; St Johnston, Daniel; Raff, Jordan W

2007-09-04

Centrosome asymmetry plays a key role in ensuring the asymmetric division of Drosophila neural stem cells (neuroblasts [NBs]) and male germline stem cells (GSCs) [1-3]. In both cases, one centrosome is anchored close to a specific cortical region during interphase, thus defining the orientation of the spindle during the ensuing mitosis. To test whether asymmetric centrosome behavior is a general feature of stem cells, we have studied female GSCs, which divide asymmetrically, producing another GSC and a cystoblast. The cystoblast then divides and matures into an oocyte, a process in which centrosomes exhibit a series of complex behaviors proposed to play a crucial role in oogenesis [4-6]. We show that the interphase centrosome does not define spindle orientation in female GSCs and that DSas-4 mutant GSCs [7], lacking centrioles and centrosomes, invariably divide asymmetrically to produce cystoblasts that proceed normally through oogenesis-remarkably, oocyte specification, microtubule organization, and mRNA localization are all unperturbed. Mature oocytes can be fertilized, but embryos that cannot support centriole replication arrest very early in development. Thus, centrosomes are dispensable for oogenesis but essential for early embryogenesis. These results reveal that asymmetric centrosome behavior is not an essential feature of stem cell divisions.

Gene expression profiling of rat spermatogonia and Sertoli cells reveals signaling pathways from stem cells to niche and testicular cancer cells to surrounding stroma

PubMed Central

2011-01-01

Background Stem cells and their niches are studied in many systems, but mammalian germ stem cells (GSC) and their niches are still poorly understood. In rat testis, spermatogonia and undifferentiated Sertoli cells proliferate before puberty, but at puberty most spermatogonia enter spermatogenesis, and Sertoli cells differentiate to support this program. Thus, pre-pubertal spermatogonia might possess GSC potential and pre-pubertal Sertoli cells niche functions. We hypothesized that the different stem cell pools at pre-puberty and maturity provide a model for the identification of stem cell and niche-specific genes. We compared the transcript profiles of spermatogonia and Sertoli cells from pre-pubertal and pubertal rats and examined how these related to genes expressed in testicular cancers, which might originate from inappropriate communication between GSCs and Sertoli cells. Results The pre-pubertal spermatogonia-specific gene set comprised known stem cell and spermatogonial stem cell (SSC) markers. Similarly, the pre-pubertal Sertoli cell-specific gene set comprised known niche gene transcripts. A large fraction of these specifically enriched transcripts encoded trans-membrane, extra-cellular, and secreted proteins highlighting stem cell to niche communication. Comparing selective gene sets established in this study with published gene expression data of testicular cancers and their stroma, we identified sets expressed genes shared between testicular tumors and pre-pubertal spermatogonia, and tumor stroma and pre-pubertal Sertoli cells with statistic significance. Conclusions Our data suggest that SSC and their niche specifically express complementary factors for cell communication and that the same factors might be implicated in the communication between tumor cells and their micro-enviroment in testicular cancer. PMID:21232125

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Myristic Acid-Modified DA7R Peptide for Whole-Process Glioma-Targeted Drug Delivery.

PubMed

Ying, Man; Wang, Songli; Zhang, Mingfei; Wang, Ruifeng; Zhu, Hangchang; Ruan, Huitong; Ran, Danni; Chai, Zhilan; Wang, Xiaoyi; Lu, Weiyue

2018-06-13

The clinical treatment of aggressive glioma has been a great challenge, mainly because of the complexity of the glioma microenvironment and the existence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hampers the effective accumulation of most therapeutic agents in the glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis, and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma-targeted drug delivery strategy was proposed. The D A7R peptide has effective BBTB-penetrating and notable glioma-, angiogenesis-, and VM-targeting abilities. Herein, we designed a myristic acid modified D A7R ligand (MC- D A7R), which combines tumor-homing D A7R with BBB-penetrable MC. MC- D A7R was then immobilized to PEGylated liposomes (MC- D A7R-LS) to form a whole-process glioma-targeting system. MC- D A7R-LS exhibited exceptional internalization in glioma, tumor neovascular, and brain capillary endothelial cells. Enhanced BBTB- and BBB-traversing efficiencies were also observed on MC- D A7R-LS. Ex vivo imaging on brain tumors also demonstrated the feasibility of MC- D A7R-LS in intracranial glioma-homing, whereas the immunofluorescence studies demonstrated its GSC and angiogenesis homing. Furthermore, doxorubicin-loaded MC- D A7R-LS accomplished a remarkable therapeutic outcome, as a result of a synergistic improvement on the glioma microenvironment. Our study highlights the potential of the MC-modified D A7R peptide as a great candidate for the whole-process glioma-targeted drug delivery.

Clinical assessment of gastric emptying and sensory function utilizing gamma scintigraphy: Establishment of reference intervals for the liquid and solid components of the Nottingham test meal in healthy subjects.

PubMed

Parker, H L; Tucker, E; Blackshaw, E; Hoad, C L; Marciani, L; Perkins, A; Menne, D; Fox, M

2017-11-01

Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study presents the reference intervals of the modular "Nottingham test meal" (NTM) for assessment of gastric function by gamma scintigraphy (GSc) in a representative population of healthy volunteers (HVs) stratified for age and sex. The NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and an optional solid component (12 solid agar-beads (0 kcal). Filling and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gamma scintigraphy parameters that describe early and late phase Gastric emptying (GE) were calculated from validated models. Gastric emptying (GE) of the liquid component was measured in 73 HVs (male 34; aged 45±20). The NTM produced normal postprandial fullness (VAS ≥30 in 41/74 subjects). Dyspeptic symptoms were rare (VAS ≥30 in 2/74 subjects). Gastric emptying half-time with the Liquid- and Solid-component -NTM was median 44 (95% reference interval 28-78) minutes and 162 (144-193) minutes, respectively. Gastric accommodation was assessed by the ratio of the liquid-NTM retained in the proximal:total stomach and by Early phase emptying assessed by gastric volume after completing the meal (GCV0). No consistent effect of anthropometric measures on GE parameters was present. Reference intervals are presented for GSc measurements of gastric motor and sensory function assessed by the NTM. Studies involving patients are required to determine whether the reference interval range offers optimal diagnostic sensitivity and specificity. © 2017 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Module Cluster: TLA-004.00 (GSC) Teaching Language Arts in the Elementary School.

ERIC Educational Resources Information Center

Mignogna, William D.

The purpose of this module cluster is to enable students to a) identify the areas that the language arts focus on in the elementary school; b) analyze and synthesize expressive and receptive skills as they relate to the language arts program; c) demonstrate a knowledge of and skill in the use of a variety of techniques and materials for teaching…

Space X1 First Entry Sample

NASA Technical Reports Server (NTRS)

James, John T.

2012-01-01

One mini-grab sample container (m-GSC) was returned aboard Space X1 because of the importance of quickly knowing first-entry conditions in this new commercial module. This sample was analyzed alongside samples of the portable clean room (PCR) used in the Space X complex at KSC. The recoveries of C-13-acetone, fluorobenzene, and chlorobenzene from the GSCs averaged 130, 129, and 132 %, respectively.

Integrated Nuclear Considerations: C&GSC Pre-Command Course Instructional Material.

DTIC Science & Technology

1980-11-21

support of TFI-12’s withdrawal to PL BOB, then to countermobiltiy and survival operations in support of BPs on PL BOB with priority to sector of TF1 -12 and...BPs 11 and 12, in order. b. Be prepared to support CATK of TF1 -12 vicinity BREITENBACH. 13. S4: a. Supervise accomplishment of task in 2, above. b

DET/MPS - THE GSFC ENERGY BALANCE PROGRAM, DIRECT ENERGY TRANSFER/MULTIMISSION SPACECRAFT MODULAR POWER SYSTEM (DEC VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

Jagielski, J. M.

1994-01-01

The DET/MPS programs model and simulate the Direct Energy Transfer and Multimission Spacecraft Modular Power System in order to aid both in design and in analysis of orbital energy balance. Typically, the DET power system has the solar array directly to the spacecraft bus, and the central building block of MPS is the Standard Power Regulator Unit. DET/MPS allows a minute-by-minute simulation of the power system's performance as it responds to various orbital parameters, focusing its output on solar array output and battery characteristics. While this package is limited in terms of orbital mechanics, it is sufficient to calculate eclipse and solar array data for circular or non-circular orbits. DET/MPS can be adjusted to run one or sequential orbits up to about one week, simulated time. These programs have been used on a variety of Goddard Space Flight Center spacecraft projects. DET/MPS is written in FORTRAN 77 with some VAX-type extensions. Any FORTRAN 77 compiler that includes VAX extensions should be able to compile and run the program with little or no modifications. The compiler must at least support free-form (or tab-delineated) source format and 'do do-while end-do' control structures. DET/MPS is available for three platforms: GSC-13374, for DEC VAX series computers running VMS, is available in DEC VAX Backup format on a 9-track 1600 BPI tape (standard distribution) or TK50 tape cartridge; GSC-13443, for UNIX-based computers, is available on a .25 inch streaming magnetic tape cartridge in UNIX tar format; and GSC-13444, for Macintosh computers running AU/X with either the NKR FORTRAN or AbSoft MacFORTRAN II compilers, is available on a 3.5 inch 800K Macintosh format diskette. Source code and test data are supplied. The UNIX version of DET requires 90K of main memory for execution. DET/MPS was developed in 1990. A/UX and Macintosh are registered trademarks of Apple Computer, Inc. VMS, DEC VAX and TK50 are trademarks of Digital Equipment Corporation. UNIX is a registered trademark of AT&T Bell Laboratories.

DET/MPS - THE GSFC ENERGY BALANCE PROGRAM, DIRECT ENERGY TRANSFER/MULTIMISSION SPACECRAFT MODULAR POWER SYSTEM (UNIX VERSION)

NASA Technical Reports Server (NTRS)

Jagielski, J. M.

1994-01-01

The DET/MPS programs model and simulate the Direct Energy Transfer and Multimission Spacecraft Modular Power System in order to aid both in design and in analysis of orbital energy balance. Typically, the DET power system has the solar array directly to the spacecraft bus, and the central building block of MPS is the Standard Power Regulator Unit. DET/MPS allows a minute-by-minute simulation of the power system's performance as it responds to various orbital parameters, focusing its output on solar array output and battery characteristics. While this package is limited in terms of orbital mechanics, it is sufficient to calculate eclipse and solar array data for circular or non-circular orbits. DET/MPS can be adjusted to run one or sequential orbits up to about one week, simulated time. These programs have been used on a variety of Goddard Space Flight Center spacecraft projects. DET/MPS is written in FORTRAN 77 with some VAX-type extensions. Any FORTRAN 77 compiler that includes VAX extensions should be able to compile and run the program with little or no modifications. The compiler must at least support free-form (or tab-delineated) source format and 'do do-while end-do' control structures. DET/MPS is available for three platforms: GSC-13374, for DEC VAX series computers running VMS, is available in DEC VAX Backup format on a 9-track 1600 BPI tape (standard distribution) or TK50 tape cartridge; GSC-13443, for UNIX-based computers, is available on a .25 inch streaming magnetic tape cartridge in UNIX tar format; and GSC-13444, for Macintosh computers running AU/X with either the NKR FORTRAN or AbSoft MacFORTRAN II compilers, is available on a 3.5 inch 800K Macintosh format diskette. Source code and test data are supplied. The UNIX version of DET requires 90K of main memory for execution. DET/MPS was developed in 1990. A/UX and Macintosh are registered trademarks of Apple Computer, Inc. VMS, DEC VAX and TK50 are trademarks of Digital Equipment Corporation. UNIX is a registered trademark of AT&T Bell Laboratories.

Light Curves and Analyses of the Eclipsing Overcontact Binaries V546 And & V566 And & the Discovery of a New Variable Star

NASA Astrophysics Data System (ADS)

Bradstreet, David H.; Sanders, S. J.; Volpert, C. G.

2013-01-01

New precision V & Rc light curves of the eclipsing binaries V546 And and V566 And have been obtained using the 41-cm telescopes at the Eastern University Observatory equipped with SBIG ST-10XME CCD’s. V546 And (GSC 2828:18, P = 0.3831 days, m = 11.2) has only one published discovery light curve with significant scatter in the data. The system was observed on seven nights from 30 Aug - 20 Sep 2012, accumulating approximately 900 observations in both V and Rc. The light curves show distinctly that the system is totally eclipsing and preliminary analysis indicates that the binary is W-type (the larger, more massive star is the cooler component), has a mass ratio of 0.34, small temperature difference between the stars of 300 K, and a fillout of 0.30. There is also strong evidence of the presence of starspots influencing the slopes of both eclipses. V566 And (GSC 2321:257, P = 0.3897 days, m = 10.9) is a totally eclipsing overcontact system likewise showing obvious O’Connell effects likely due to starspots. V566 And was observed on seven nights from 30 Aug - 25 Sep 2012, accumulating more than 900 observations in both V and Rc. Preliminary light curve models indicate a W-type system with a small temperature difference between the stars of 200 K and a mass ratio of only 0.20. The original comparison star for V566 And, GSC 2321:911 (m = 12.0), turned out to be a previously unknown variable star with a period of approximately 0.466 days and a light amplitude in Rc of 0.15 mag. This new variable has no information concerning it in the online archives and initial analysis seems to indicate that this may be an ellipsoidal variable. The complete light curve analyses will be presented for both systems and the new variable’s light curves will also be discussed.

DET/MPS - THE GSFC ENERGY BALANCE PROGRAM, DIRECT ENERGY TRANSFER/MULTIMISSION SPACECRAFT MODULAR POWER SYSTEM (MACINTOSH A/UX VERSION)

NASA Technical Reports Server (NTRS)

Jagielski, J. M.

1994-01-01

The DET/MPS programs model and simulate the Direct Energy Transfer and Multimission Spacecraft Modular Power System in order to aid both in design and in analysis of orbital energy balance. Typically, the DET power system has the solar array directly to the spacecraft bus, and the central building block of MPS is the Standard Power Regulator Unit. DET/MPS allows a minute-by-minute simulation of the power system's performance as it responds to various orbital parameters, focusing its output on solar array output and battery characteristics. While this package is limited in terms of orbital mechanics, it is sufficient to calculate eclipse and solar array data for circular or non-circular orbits. DET/MPS can be adjusted to run one or sequential orbits up to about one week, simulated time. These programs have been used on a variety of Goddard Space Flight Center spacecraft projects. DET/MPS is written in FORTRAN 77 with some VAX-type extensions. Any FORTRAN 77 compiler that includes VAX extensions should be able to compile and run the program with little or no modifications. The compiler must at least support free-form (or tab-delineated) source format and 'do do-while end-do' control structures. DET/MPS is available for three platforms: GSC-13374, for DEC VAX series computers running VMS, is available in DEC VAX Backup format on a 9-track 1600 BPI tape (standard distribution) or TK50 tape cartridge; GSC-13443, for UNIX-based computers, is available on a .25 inch streaming magnetic tape cartridge in UNIX tar format; and GSC-13444, for Macintosh computers running AU/X with either the NKR FORTRAN or AbSoft MacFORTRAN II compilers, is available on a 3.5 inch 800K Macintosh format diskette. Source code and test data are supplied. The UNIX version of DET requires 90K of main memory for execution. DET/MPS was developed in 1990. A/UX and Macintosh are registered trademarks of Apple Computer, Inc. VMS, DEC VAX and TK50 are trademarks of Digital Equipment Corporation. UNIX is a registered trademark of AT&T Bell Laboratories.

Resveratrol Targets AKT and p53 in Glioblastoma and Glioblastoma Stem-like Cells to Suppress Growth and Infiltration

PubMed Central

Clark, Paul A.; Bhattacharya, Saswati; Elmayan, Ardem; Darjatmoko, Soesiawati R.; Thuro, Bradley A.; Yan, Michael B.; van Ginkel, Paul R.; Polans, Arthur S.; Kuo, John S.

2016-01-01

Object Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than two years with current treatment. GBM exhibits extensive intra-tumor and inter-patient heterogeneity, suggesting that successful therapies should exert broad anti-cancer activities. Therefore, the natural non-toxic pleiotropic agent, resveratrol, was studied for anti-tumorigenic effects against GBM. Methods Resveratrol’s effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma. Results Resveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability of GSCs, suggesting anti-stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel transwell assay at doses similar to those mediating anti-proliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intra-tumor or peri-tumor resveratrol injection further suppressed growth and approximating tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared to intravenous delivery, and with no apparent toxicity. Conclusions Resveratrol potently inhibited GBM and GBM stem-like cell growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other anti-tumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e. convection enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in brain. Resveratrol’s non-toxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies. PMID:27419830

Preliminary Studies of Interacting Binaries From NURO Observations : V963 Cygni and GSC 1419 0091

NASA Astrophysics Data System (ADS)

Samec, R. G.; Jones, S. M.; Scott, T.; Branning, J.; Miller, J.; Faulkner, D. R.; Hawkins, N. C.

2005-12-01

We present preliminary analyses of V963 and V965 Cygni based on observations taken at the National Undergraduate Research Observatory (NURO). Our CCD observations were taken 07-12 March 2005 and 19-25 July 2004 by DRF,RGS, and NCH with the Lowell Observatory 31-inch reflector. Standard UBVRI filters were used. Preliminary light curve analyses and updated periodicity studies are presented for these variables. V963 Cyg (GSC 2656 1995,α (2000) = 19h 44m 04.92s, δ (2000) = +31 41 50.17) is a detached binary discovered by Wachmann (Ast Abh Ham St VI, #1, 1961). The eclipse depths are nearly equal, 0.78 and 0.67 magnitudes in in V in the primary and secondary eclipses, respectively, causing observers to MISTAKINGLY classify it as an Algol-type system. Thus the two stars are similar in temperature and the period has to be DOUBLED. The curves appear fairlysymmetrical with a depressed section following the primary eclipse in R and I about 0.2 phase units wide. In BVRI, 100 to 130 observations were taken along with 75 in U. We determined three new times of minimum light, two secondary eclipses, HJD Min II = 2453207.76857±0.00029d and 2453211.9540±0.0032d, and one primary eclipse HJD Min I = 2453209.86073±0.00095d. A corrected period and an improved ephemeris was computed using available times of minimum light: HJD Min I = 2453209.8616(±0.0011)d + 1.39466792(±0.00000019)*E. GSC 1419 0091 (Brh V132) [α (2000) = 10h 11m 59.152s,δ (2000) = +16 52 30.28] is an overcontact binary discovered by Klaus Bernhard (BAV, http://www.var-mo.de/star/brh_v132.htm). We took approximately 60-65 observations in each of B,V,R, and I. We determined four new times of minimum light: HJD Min I = 2453437.8293(±0.0003) and 2453441.8291(±0.0019), and HJD Min II = 2453437.6973(±0.0012) and 2453442.76317(±0.0005). We computed an improved ephemeris from all available times of minimum and low light: HJD Min I = 2452754.4733(±0.0030)d + 0.2667251*E(±0.0000011). The light curves show shallow eclipse amplitudes of 0.46 and 0.43 mags in B and V, respectively, and a time of constant light in the secondary eclipse of 31 m. We wish to thank the NURO for their allocation of observing time, as well as NASA and the American Astronomical Society for their support in paying for travel and publication expenses.

Review of the Contribution of the Scottish Science Centres Network to Formal and Informal Science Education: Report of Follow-Through Visits by HM Inspectorate of Education--June 2009

ERIC Educational Resources Information Center

Her Majesty's Inspectorate of Education, 2009

2009-01-01

In 2006, the Scottish Executive's Enterprise, Transport and Lifelong Learning Department (SEETLLD) asked HM Inspectorate of Education (HMIE) to carry out a review of the four Scottish science centres--Glasgow Science Centre (GSC), Our Dynamic Earth (ODE) in Edinburgh, Satrosphere Science Centre in Aberdeen, and Sensation Science Centre in Dundee.…

Stepping-Motion Motor-Control Subsystem For Testing Bearings

NASA Technical Reports Server (NTRS)

Powers, Charles E.

1992-01-01

Control subsystem closed-loop angular-position-control system causing motor and bearing under test to undergo any of variety of continuous or stepping motions. Also used to test bearing-and-motor assemblies, motors, angular-position sensors including rotating shafts, and like. Monitoring subsystem gathers data used to evaluate performance of bearing or other article under test. Monitoring subsystem described in article, "Monitoring Subsystem For Testing Bearings" (GSC-13432).

STS 133 Return Samples: Air Quality Aboard Shuttle (STS-133) and International Space Station (ULFS)

NASA Technical Reports Server (NTRS)

James, John T.

2011-01-01

The toxicological assessments of 2 canisters (mini-GSC or GSCs) from the Shuttle are reported. Analytical methods have not changed from earlier reports. The percent recoveries of the 3 surrogates (C-13-acetone, fluorobenzene, and chlorobenzene) from the 2 Shuttle GSCs averaged 86, 100, and 87, respectively. Based on the end-of-mission sample, the Shuttle atmosphere was acceptable for human respiration.

Enhancing Nanos expression via the bacterial TomO protein is a conserved strategy used by the symbiont Wolbachia to fuel germ stem cell maintenance in infected Drosophila females.

PubMed

Ote, Manabu; Yamamoto, Daisuke

2018-04-27

The toxic manipulator of oogenesis (TomO) protein has been identified in the wMel strain of Wolbachia that symbioses with the vinegar fly Drosophila melanogaster, as a protein that affects host reproduction. TomO protects germ stem cells (GSCs) from degeneration, which otherwise occurs in ovaries of host females that are mutant for the gene Sex-lethal (Sxl). We isolated the TomO homologs from wPip, a Wolbachia strain from the mosquito Culex quinquefasciatus. One of the homologs, TomO w Pip 1, exerted the GSC rescue activity in fly Sxl mutants when lacking its hydrophobic stretches. The GSC-rescuing action of the TomO w Pip 1 variant was ascribable to its abilities to associate with Nanos (nos) mRNA and to enhance Nos protein expression. The analysis of structure-activity relationships with TomO homologs and TomO deletion variants revealed distinct modules in the protein that are each dedicated to different functions, i.e., subcellular localization, nos mRNA binding or Nos expression enhancement. We propose that modular reshuffling is the basis for structural and functional diversification of TomO protein members. © 2018 Wiley Periodicals, Inc.

Time-Domain Pure-state Polarization Analysis of Surface Waves Traversing California

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

Zhang, J; Walter, W R; Lay, T

A time-domain pure-state polarization analysis method is used to characterize surface waves traversing California parallel to the plate boundary. The method is applied to data recorded at four broadband stations in California from twenty-six large, shallow earthquakes which occurred since 1988, yielding polarization parameters such as the ellipticity, Euler angles, instantaneous periods, and wave incident azimuths. The earthquakes are located along the circum-Pacific margin and the ray paths cluster into two groups, with great-circle paths connecting stations MHC and PAS or CMB and GSC. The first path (MHC-PAS) is in the vicinity of the San Andreas Fault System (SAFS), andmore » the second (CMB-GSC) traverses the Sierra Nevada Batholith parallel to and east of the SAFS. Both Rayleigh and Love wave data show refractions due to lateral velocity heterogeneities under the path, indicating that accurate phase velocity and attenuation analysis requires array measurements. The Rayleigh waves are strongly affected by low velocity anomalies beneath Central California, with ray paths bending eastward as waves travel toward the south, while Love waves are less affected, providing observables to constrain the depth extent of the anomalies. Strong lateral gradients in the lithospheric structure between the continent and the ocean are the likely cause of the path deflections.« less

Community cyberinfrastructure for Advanced Microbial Ecology Research and Analysis: the CAMERA resource

PubMed Central

Sun, Shulei; Chen, Jing; Li, Weizhong; Altintas, Ilkay; Lin, Abel; Peltier, Steve; Stocks, Karen; Allen, Eric E.; Ellisman, Mark; Grethe, Jeffrey; Wooley, John

2011-01-01

The Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA, http://camera.calit2.net/) is a database and associated computational infrastructure that provides a single system for depositing, locating, analyzing, visualizing and sharing data about microbial biology through an advanced web-based analysis portal. CAMERA collects and links metadata relevant to environmental metagenome data sets with annotation in a semantically-aware environment allowing users to write expressive semantic queries against the database. To meet the needs of the research community, users are able to query metadata categories such as habitat, sample type, time, location and other environmental physicochemical parameters. CAMERA is compliant with the standards promulgated by the Genomic Standards Consortium (GSC), and sustains a role within the GSC in extending standards for content and format of the metagenomic data and metadata and its submission to the CAMERA repository. To ensure wide, ready access to data and annotation, CAMERA also provides data submission tools to allow researchers to share and forward data to other metagenomics sites and community data archives such as GenBank. It has multiple interfaces for easy submission of large or complex data sets, and supports pre-registration of samples for sequencing. CAMERA integrates a growing list of tools and viewers for querying, analyzing, annotating and comparing metagenome and genome data. PMID:21045053

Community cyberinfrastructure for Advanced Microbial Ecology Research and Analysis: the CAMERA resource.

PubMed

Sun, Shulei; Chen, Jing; Li, Weizhong; Altintas, Ilkay; Lin, Abel; Peltier, Steve; Stocks, Karen; Allen, Eric E; Ellisman, Mark; Grethe, Jeffrey; Wooley, John

2011-01-01

The Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA, http://camera.calit2.net/) is a database and associated computational infrastructure that provides a single system for depositing, locating, analyzing, visualizing and sharing data about microbial biology through an advanced web-based analysis portal. CAMERA collects and links metadata relevant to environmental metagenome data sets with annotation in a semantically-aware environment allowing users to write expressive semantic queries against the database. To meet the needs of the research community, users are able to query metadata categories such as habitat, sample type, time, location and other environmental physicochemical parameters. CAMERA is compliant with the standards promulgated by the Genomic Standards Consortium (GSC), and sustains a role within the GSC in extending standards for content and format of the metagenomic data and metadata and its submission to the CAMERA repository. To ensure wide, ready access to data and annotation, CAMERA also provides data submission tools to allow researchers to share and forward data to other metagenomics sites and community data archives such as GenBank. It has multiple interfaces for easy submission of large or complex data sets, and supports pre-registration of samples for sequencing. CAMERA integrates a growing list of tools and viewers for querying, analyzing, annotating and comparing metagenome and genome data.

A PROPELLER-EFFECT INTERPRETATION OF MAXI/GSC LIGHT CURVES OF 4U 1608-52 AND Aql X-1 AND APPLICATION TO XTE J1701-462

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

Asai, K.; Matsuoka, M.; Mihara, T.

2013-08-20

We present the luminosity dwell-time distributions during the hard states of two low-mass X-ray binaries containing a neutron star (NS), 4U 1608-52 and Aql X-1, observed with MAXI/GSC. The luminosity distributions show a steep cutoff on the low-luminosity side at {approx}1.0 Multiplication-Sign 10{sup 36} erg s{sup -1} in both sources. The cutoff implies a rapid luminosity decrease in their outburst decay phases and this decrease can be interpreted as being due to the propeller effect. We estimate the surface magnetic field of 4U 1608-52 to be (0.5-1.6) Multiplication-Sign 10{sup 8} G and Aql X-1 to be (0.6-1.9) Multiplication-Sign 10{sup 8}more » G from the cutoff luminosity and apply the same propeller mechanism to the similar rapid luminosity decrease observed in the transient Z source, XTE J1701-462, with RXTE/ASM. Assuming that the spin period of the NS is on the order of milliseconds, the observed cutoff luminosity implies a surface magnetic field on the order of 10{sup 9} G.« less

Detailed evaluation of gas hydrate reservoir properties using JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well downhole well-log displays

USGS Publications Warehouse

Collett, T.S.

1999-01-01

The JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well project was designed to investigate the occurrence of in situ natural gas hydrate in the Mallik area of the Mackenzie Delta of Canada. Because gas hydrate is unstable at surface pressure and temperature conditions, a major emphasis was placed on the downhole logging program to determine the in situ physical properties of the gas-hydrate-bearing sediments. Downhole logging tool strings deployed in the Mallik 2L-38 well included the Schlumberger Platform Express with a high resolution laterolog, Array Induction Imager Tool, Dipole Shear Sonic Imager, and a Fullbore Formation Microlmager. The downhole log data obtained from the log- and core-inferred gas-hydrate-bearing sedimentary interval (897.25-1109.5 m log depth) in the Mallik 2L-38 well is depicted in a series of well displays. Also shown are numerous reservoir parameters, including gas hydrate saturation and sediment porosity log traces, calculated from available downhole well-log and core data. The gas hydrate accumulation delineated by the Mallik 2L-38 well has been determined to contain as much as 4.15109 m3 of gas in the 1 km2 area surrounding the drill site.

Geologic mapping on the deep seafloor: Reconstructing lava flow emplacement and eruptive history at the Galápagos Spreading Center

NASA Astrophysics Data System (ADS)

McClinton, J. T.; White, S.; Colman, A.; Sinton, J. M.; Bowles, J. A.

2012-12-01

The deep seafloor imposes significant difficulties on data collection that require the integration of multiple data sets and the implementation of unconventional geologic mapping techniques. We combine visual mapping of geological contacts by submersible with lava flow morphology maps and relative and absolute age constraints to create a spatiotemporal framework for examining submarine lava flow emplacement at the intermediate-spreading, hotspot-affected Galápagos Spreading Center (GSC). We mapped 18 lava flow fields, interpreted to be separate eruptive episodes, within two study areas at the GSC using visual observations of superposition, surface preservation and sediment cover from submersible and towed camera surveys, augmented by high-resolution sonar surveys and sample petrology [Colman et al., Effects of variable magma supply on mid-ocean ridge eruptions: Constraints from mapped lava flow fields along the Galápagos Spreading Center; 2012 G3]. We also mapped the lava flow morphology within the majority of these eruptive units using an automated, machine-learning classification method [McClinton et al., Neuro-fuzzy classification of submarine lava flow morphology; 2012 PE&RS]. The method combines detailed geometric, acoustic, and textural attributes derived from high-resolution sonar data with visual observations and a machine-learning algorithm to classify submarine lava flow morphology as pillows, lobates, or sheets. The resulting lava morphology maps are a valuable tool for interpreting patterns in the emplacement of submarine lava flows at a mid-ocean ridge (MOR). Within our study area at 92°W, where the GSC has a relatively high magma supply, high effusion rate sheet and lobate lavas are more abundant in the oldest mapped eruptive units, while the most recent eruptions mostly consist of low effusion rate pillow lavas. The older eruptions (roughly 400yrs BP by paleomagnetic intensity) extend up to 1km off axis via prominent channels and tubes, while the most recent eruptions (<100yrs BP by paleomagnetic intensity) are mainly on-axis pillow ridges and domes. These spatial and temporal trends suggest a gradual transition from low-relief, "paving" eruptions to relief-building, "constructional" eruptions. In our second study area at 95°W, where magma supply is lower, eruptions mostly consist of axial seamounts and irregularly shaped clusters of pillow mounds. Many have summit plateaus with inflated, partially collapsed lobate lavas suggesting variable effusion rates and topographic influence on lava flows. In addition, a relatively extensive (~9.5km2) flow field of inflated lobate and sheet lavas erupted from vents ~1km north of the ridge axis and flowed ~1km into the inner axial graben through channels and tubes, ponding against older structures and leaving prominent "bathtub rings" and collapse features. This eruption provides direct evidence that large, high effusion rate eruptions can occur in low magma supply settings at MORs.

Interleukin-13 conjugated quantum dots for identification of glioma initiating cells and their extracellular vesicles.

PubMed

Madhankumar, A B; Mrowczynski, Oliver D; Patel, Suhag R; Weston, Cody L; Zacharia, Brad E; Glantz, Michael J; Siedlecki, Christopher A; Xu, Li-Chong; Connor, James R

2017-08-01

Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study. The exosomes were isolated from the GSC conditioned medium and the expression of IL13Rα2 in the GSC and exosomes was verified. The binding property of IL13QD to the tumor associated exosomes was initially confirmed by transmission electron microscopy. The force of attraction between the quantum dots and U251 glioma cells and the exosomes was investigated by atomic force microscopy, which indicated a higher force of binding interaction between the IL13QD and IL13Rα2 expressing glioma cells and exosomes secreted by glioma stem cells. Flow cytometry of the IL13QD and exosomes from the culture media and cerebrospinal fluid (CSF) of patients with glioma tumors indicated a distinctly populated complex pattern different from that of non-targeted quantum dots and bovine serum albumin (BSA) conjugated quantum dots confirming specific binding potential of the IL13QD to the tumor associated exosomes. The results of this study demonstrate that IL13QD can serve as an ex vivo marker for glioma stem cells and exosomes that can inform diagnosis and prognosis of patients harboring malignant disease. Functionalized quantum dots are flexible semiconductor nanomaterials which have an immense application in biomedical research. In particular, when they are functionalized with biomolecules like proteins or antibodies, they have the specialized ability to detect the expression of receptors and antigens in cells and tissues. In this study we designed a cytokine (interleukin-13) functionalized quantum dot to detect a cancer associated receptor expressed in cancer stem cells and the extracellular vesicles (exosomes) secreted by the cancer cells themselves. The binding pattern of these cytokine modified quantum dots to the cancer stem cells and exosomes alters the physical properties of the complex in the fixed and suspended form. This altered binding pattern can be monitored by a variety of techniques, including transmission electron microscopy, atomic force microscopy and flow cytometry, and subsequent characterization of this quantum dot binding profile provides useful data that can be utilized as a fingerprint to detect cancer disease progression. This type of functionalized quantum dot fingerprint is especially useful for invasive cancers including brain and other metastatic cancers and may allow for earlier detection of disease progression or recurrence, thus saving the lives of patients suffering from this devastating disease. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Geochemistry of Intra-Transform Lavas from the Galápagos Transform Fault

NASA Astrophysics Data System (ADS)

Morrow, T. A.; Mittelstaedt, E. L.; Harpp, K. S.

2013-12-01

The Galápagos plume has profoundly affected the development and evolution of the nearby (<250 km) Galápagos Transform Fault (GTF), a ~100km right-stepping offset in the Galápagos Spreading Center (GSC). The GTF can be divided into two sections that represent different stages of transform evolution: the northern section exhibits fully developed transform fault morphology, whereas the southern section is young, and deformation is more diffuse. Both segments are faulted extensively and include numerous small (<0.5km3) monogenetic volcanic cones, though volcanic activity is more common in the south. To examine the composition of the mantle source and melting conditions responsible for the intra-transform lavas, as well as the influence of the plume on GTF evolution, we present major element, trace element, and radiogenic isotope analysis of samples collected during SON0158, EWI0004, and MV1007 cruises. Radiogenic isotope ratio variations in the Galápagos Archipelago require four distinct mantle reservoirs across the region: PLUME, DM, FLO, and WD. We find that Galápagos Transform lavas are chemically distinct from nearby GSC lavas and neighboring seamounts. They have radiogenic isotopic compositions that lie on a mixing line between DM and PLUME, with little to no contribution from any other mantle reservoirs despite their geographic proximity to WD-influenced lavas erupted along the GSC and at nearby (<50km away) seamounts. Within the transform, lavas from the northern section are more enriched in radiogenic isotopes than lavas sampled in the southern section. Transform lavas are anomalously depleted in incompatible trace elements (ITEs) relative to GSC lavas, suggesting unique melting conditions within the transform. Isotopic variability along the transform axis indicates that mantle sources and/or melting mechanisms vary between the northern and southern sections, which may relate to their distances from the plume or the two-stage development and evolution of the Galápagos Transform Fault. We present a melting model that reproduces GTF lava chemistry from a mixture of two partial melts of PLUME and DM. We assume that the DM source has an ITE composition similar to the depleted upper mantle, melting is purely fractional, and lavas do not fractionate during ascent. Solutions were achieved using a Metropolis algorithm and constrained by observed GTF lava chemistry. Model results predict that GTF lavas are produced by a mixture of a ~3%×1% partial melt of the PLUME source and a ~5%×4% partial melt of the DM source. Our model predicts that a larger proportion of PLUME melts contribute to GTF lavas than DM melts. Absence of the WD component and relatively low concentrations of ITEs may indicate that lavas in the GTF are produced from a source that has already undergone partial melting and is being re-melted beneath the TF. Re-melting may be caused by extension across the GTF, or development of the southern section of the GTF via the ~1Ma ridge jump.

The Identification and Cloning of the Wnt-1 Receptor

DTIC Science & Technology

1996-10-01

examination of embryos with duplicated axes revealed that Xwnt-5A and hFz5 induced a full array of dorsal tissues, including notochord , neural tube...tube, a notochord and somites in both axes. c). Xwnt-5A plus hfz5 induce ectopic goosecoid (gsc) expression in stage 11 embryos, as visualized by whole...Lai CJ, Olson DJ, Kelly GM: Dissecting Wnt signalling pathways and Wnt-sensitive developmental processes through transient misexpression analyses in

MicroRNA-137 is downregulated in glioblastoma and inhibits the stemness of glioma stem cells by targeting RTVP-1

PubMed Central

Bier, Ariel; Giladi, Nis; Kronfeld, Noam; Lee, Hae Kyung; Cazacu, Simona; Finniss, Susan; Xiang, Cunli; Poisson, Laila; deCarvalho, Ana C.; Slavin, Shimon; Jacoby, Elad; Yalon, Michal; Toren, Amos; Mikkelsen, Tom; Brodie, Chaya

2013-01-01

Glioblastomas (GBM), the most common and aggressive malignant astrocytic tumors, contain a small subpopulation of cancer stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Here, we study the expression and function of miR-137, a putative suppressor miRNA, in GBM and GSCs. We found that the expression of miR-137 was significantly lower in GBM and GSCs compared to normal brains and neural stem cells (NSCs) and that the miR-137 promoter was hypermethylated in the GBM specimens. The expression of miR-137 was increased in differentiated NSCs and GSCs and overexpression of miR-137 promoted the neural differentiation of both cell types. Moreover, pre-miR-137 significantly decreased the self-renewal of GSCs and the stem cell markers Oct4, Nanog, Sox2 and Shh. We identified RTVP-1 as a novel target of miR-137 in GSCs; transfection of the cells with miR-137 decreased the expression of RTVP-1 and the luciferase activity of RTVP-1 3'-UTR reporter plasmid. Furthermore, overexpression of RTVP-1 plasmid lacking its 3'-UTR abrogated the inhibitory effect of miR-137 on the self-renewal of GSCs. Silencing of RTVP-1 decreased the self-renewal of GSCs and the expression of CXCR4 and overexpression of CXCR4 abrogated the inhibitory effect of RTVP-1 silencing on GSC self-renewal. These results demonstrate that miR-137 is downregulated in GBM probably due to promoter hypermethylation. miR-137 inhibits GSC self-renewal and promotes their differentiation by targeting RTVP-1 which downregulates CXCR4. Thus, miR-137 and RTVP-1 are attractive therapeutic targets for the eradication of GSCs and for the treatment of GBM. PMID:23714687

A cell-penetrating peptide based on the interaction between c-Src and connexin43 reverses glioma stem cell phenotype

PubMed Central

Gangoso, E; Thirant, C; Chneiweiss, H; Medina, J M; Tabernero, A

2014-01-01

Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is downregulated in malignant gliomas. These tumors are composed of a heterogeneous population of cells that include many with stem-cell-like properties, called glioma stem cells (GSCs), which are highly tumorigenic and lack Cx43 expression. Interestingly, restoring Cx43 reverses GSC phenotype and consequently reduces their tumorigenicity. In this study, we investigated the mechanism by which Cx43 exerts its antitumorigenic effects on GSCs. We have focused on the tyrosine kinase c-Src, which interacts with the intracellular carboxy tail of Cx43. We found that Cx43 regulates c-Src activity and proliferation in human GSCs expanded in adherent culture. Thus, restoring Cx43 in GSCs inhibited c-Src activity, which in turn promoted the downregulation of the inhibitor of differentiation Id1. Id1 sustains stem cell phenotype as it controls the expression of Sox2, responsible for stem cell self-renewal, and promotes cadherin switching, which has been associated to epithelial–mesenchymal transition. Our results show that both the ectopic expression of Cx43 and the inhibition of c-Src reduced Id1, Sox2 expression and promoted the switch from N- to E-cadherin, suggesting that Cx43, by inhibiting c-Src, downregulates Id1 with the subsequent changes in stem cell phenotype. On the basis of this mechanism, we found that a cell-penetrating peptide, containing the region of Cx43 that interacts with c-Src, mimics the effect of Cx43 on GSC phenotype, confirming the relevance of the interaction between Cx43 and c-Src in the regulation of the malignant phenotype and pinpointing this interaction as a promising therapeutic target. PMID:24457967

GSC 4232.2850, a new eclipsing binary with elliptical orbit

NASA Astrophysics Data System (ADS)

Goranskij, V.; Shugarov, S.; Kroll, P.; Golovin, A.

2005-04-01

GSC 4232.2830 (20h 01m 28s.407, +61? 10' 17".18, 2000.0, v=12m.1) was suspected to be an eclipsing binary by VPG in the routine overview of photographical plates taken with 40-cm astrograph of SAI Crimean station. To define orbital elements of the binary, we searched for observations in Sonneberg Observatory plate collection, NSVS database (Wozniak et al., 2004), and carried out visual monitoring with a small telescope equipped with an electronic image tube, an analogue of a night vision device. Later, when we had found a preliminary solution, we carried out accurate CCD photometry to improve the orbital elements. We should note, that the depths of eclipses in the NSVS database do not exceed 0m.2, what contradicts to other observations. We suppose that NSVS measurements concern to integral light of two stars, a variable star, and a nearby brighter star, GSC 4232.2395, due to low resolution of this survey, 72". Using all the available observations we found the single orbital solution with an elliptical orbit and the period of 11,6 day. The center of the secondary minimum occurs at the orbital phase 0.69835 or 8.1 day after the primary minimum. The improved ephemeris derived using accurate CCD observations is following: HJD Min I = 2453278,3185(2) + 11.628188 (5) x E. O-C analysis does not show orbital period variations during the time interval of observations, or any evidence of apsidal motion. The observations show that both eclipses have about equal depth 0m.60, but essentially different duration, 0p.028 (7 h.8) for Min I, and 0 p.0175 (4 h.9) for Min II. The eclipses are partial. CCD photometry gives mean colors U-B = -0 m.06, B-V = 0 m.57, and V-R = 0 m.50 without notable color variations in the eclipse phases. Old Sonneberg photographic observations indicate that the eclipses were shallower in the middle of the past century than in the present time! Such contradictions may suggest that the depth of eclipses varied, as in the well-known system SSLac (Mossakovskaja, 1993; Milone et al, 2000; Torres and Stefanic, 2001). The eclipse depth variations should be verified with more precise observations taken during the longer time interval.

USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance

PubMed Central

Lee, Jin-Ku; Chang, Nakho; Yoon, Yeup; Yang, Heekyoung; Cho, Heejin; Kim, Eunhee; Shin, Yongjae; Kang, Wonyoung; Oh, Young Taek; Mun, Gyeong In; Joo, Kyeung Min; Nam, Do-Hyun; Lee, Jeongwu

2016-01-01

Background Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. Methods We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. Results USP1 was highly expressed in gliomas relative to normal brain tissues and more preferentially in GSC enrichment marker (CD133 or CD15) positive cells. USP1 positively regulated the protein stability of the ID1 and CHEK1, critical regulators of DNA damage response and stem cell maintenance. Targeting USP1 by RNA interference or treatment with a chemical USP1 inhibitor attenuated clonogenic growth and survival of GSCs and enhanced radiosensitivity of GBM cells. Finally, USP1 inhibition alone or in combination with radiation significantly prolonged the survival of tumor-bearing mice. Conclusion USP1-mediated protein stabilization promotes GSC maintenance and treatment resistance, thereby providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM. PMID:26032834

Axial high topography and partial melt in the crust and mantle beneath the western Galápagos Spreading Center

USGS Publications Warehouse

Blacic, Tanya M.; Ito, Garrett; Shah, Anjana K.; Canales, Juan Pablo; Lin, Jian

2008-01-01

The hot spot-influenced western Galápagos Spreading Center (GSC) has an axial topographic high that reaches heights of ∼700 m relative to seafloor depth ∼25 km from the axis. We investigate the cause of the unusual size of the axial high using a model that determines the flexural response to loads resulting from the thermal and magmatic structure of the lithosphere. The thermal structure simulated is appropriate for large amounts of cooling by hydrothermal circulation, which tends to minimize the amount of partial melt needed to explain the axial topography. Nonetheless, results reveal that the large axial high near 92°W requires that either the crust below the magma lens contains >35% partial melt or that 20% melt is present in the lower crust and at least 3% in the mantle within a narrow column (<∼10 km wide) extending to depths of 45–65 km. Because melt fractions >35% in the crust are considered unreasonable, it is likely that much of the axial high region of the GSC is underlain by a narrow region of partially molten mantle of widths approaching those imaged seismically beneath the East Pacific Rise. A narrow zone of mantle upwelling and melting, driven largely by melt buoyancy, is a plausible explanation.

Observations and light curve solutions of a selection of middle-contact W UMa binaries

NASA Astrophysics Data System (ADS)

Kjurkchieva, Diana Petrova; Popov, Velimir Angelov; Lyubenova Vasileva, Doroteya; Petrov, Nikola Ivanov

2018-04-01

Photometric observations in Sloan g‧ and i‧ bands of W UMa binaries NSVS 4340949, T-Dra0–00959, GSC 03950–00707, NSVS 4665041, NSVS 4803568, MM Peg, MM Com and NSVS 4751449 are presented. The light curve solutions revealed that the components of each target are of G and K spectral types. The binaries of the sample have middle-contact configurations whose fillout factors are within the range 0.2–0.4. The only exception is NSVS 4751449 which is in deeper contact (fillout factor of 0.55). It precisely obeys the relation between mass ratio and fillout factor for deep, low mass ratio overcontact binaries. One of the eclipses of almost all targets (except MM Peg) is an occultation and their photometric mass ratios and solutions could be accepted with confidence. We found that the target components have almost equal temperatures but differ considerably in size and mass. The components of the partially-eclipsed MM Peg have close parameters. Our solutions reveal that NSVS 4340949, T-Dra0–00959, NSVS 4803568 and MM Com are of W subtype while GSC 03950–00707, NSVS 4665041, MM Peg and NSVS 4751449 are of A subtype. This subclassification is well-determined for all totally-eclipsed binaries. The targets confirm the trends in which W-subtype systems have smaller periods and lower temperatures than A subtype binaries.

The distribution of near-axis seamounts at intermediate spreading ridges

NASA Astrophysics Data System (ADS)

Howell, J. K.; Bohnenstiehl, D. R.; White, S. M.; Supak, S. K.

2008-12-01

The ridge axes along the intermediate-spreading rate Galapagos Spreading Center (GSC, 46-56 mm/yr) and South East Indian Ridge (SEIR, 72-76 mm/yr) vary from rifted axial valleys to inflated axial highs independent of spreading rate. The delivery and storage of melt is believed to control axial morphology, with axial highs typically observed in areas underlain by a shallow melt lens and axial valleys in areas without a significant melt lens [e.g., Baran et al., 2005 G-cubed; Detrick et al. 2002 G-cubed]. To investigate a possible correlation between the style of seafloor volcanism and axial morphology, a closed contour algorithm is used to identify near axis (2.5km off axis) semi-circular seamounts of heights greater than 20m from shipboard multibeam bathymetry. In areas characterized by an axial high, more seamounts are formed at the ends of the segments than in the center. This is consistent with observations at fast-spreading ridges and suggests a tendency of lavas to erupt at lower effusion rates near second-order segment boundaries. Segments with a rift valley along the GSC show the opposite trend, with more seamounts at the center of second-order segments. Both patterns however are observed along SEIR segments with rift valleys where magma supply may be reflected in size and not their abundance.

VizieR Online Data Catalog: Vatican Emission-line stars (Coyne+ 1974-1983)

NASA Astrophysics Data System (ADS)

Coyne, G. V.; Lee, T. A.; de Graeve, E.; Wisniewski, W.; Corbally, C.; Otten, L. B.; MacConnell, D. J.

2009-10-01

The survey represents a search for Hα emission-line stars, and was conducted with a 12{deg} objective prism on the Vatican Schmidt telescope. The Vatican Emission Stars (VES) survey covers the galactic plane (|b|<=5{deg}) between galactic longitudes 58 and 174{deg}. The catalog was re-examined by B. Skiff (Lowell Observatory), and tne VES stars were cross-identified with modern surveys: GSC (Cat. I/255), Tycho-2 (I/256), 2MASS (II/246), IRAS point source catalog (II/125), MSX6C (V/114), CMC14 (I/304), GSC-2.3 (I/305), UCAC2 (I/289). Cross-identifications are also supplied with HD/BD/GCVS names, and with Dearborn catalog of red stars (II/68). Many of the stars in the first four papers are not early-type emission-line stars, but instead M giants, where the sharp TiO bandhead at 6544{AA} was mistaken for H-{alpha} emission on the objective-prism plates. Based on the revision of paper V and a later list prepared by Jack MacConnell, a column identifies the "non H-alpha" stars explicitly. The links with the Dearborn, IRAS, and MSX catalogues help identify the red stars. These and other identifications and comments are given in the remarks at the end of each line, or in longer notes in a separate file, indicated by an asterisk (*) next to the star number. (3 data files).

VizieR Online Data Catalog: Vatican Emission-line stars (Coyne+ 1974-1983)

NASA Astrophysics Data System (ADS)

Coyne, G. V.; Lee, T. A.; de Graeve, E.; Wisniewski, W.; Corbally, C.; Otten, L. B.; MacConnell, D. J.

2008-03-01

The survey represents a search for Hα emission-line stars, and was conducted with a 12{deg} objective prism on the Vatican Schmidt telescope. The Vatican Emission Stars (VES) survey covers the galactic plane (|b|<=5{deg}) between galactic longitudes 58 and 174{deg}. The catalog was re-examined by B. Skiff (Lowell Observatory), and tne VES stars were cross-identified with modern surveys: GSC (Cat. I/255), Tycho-2 (I/256), 2MASS (II/246), IRAS point source catalog (II/125), MSX6C (V/114), CMC14 (I/304), GSC-2.3 (I/305), UCAC2 (I/289). Cross-identifications are also supplied with HD/BD/GCVS names, and with Dearborn catalog of red stars (II/68). Many of the stars in the first four papers are not early-type emission-line stars, but instead M giants, where the sharp TiO bandhead at 6544{AA} was mistaken for H-{alpha} emission on the objective-prism plates. Based on the revision of paper V and a later list prepared by Jack MacConnell, a column identifies the "non H-alpha" stars explicitly. The links with the Dearborn, IRAS, and MSX catalogues help identify the red stars. These and other identifications and comments are given in the remarks at the end of each line, or in longer notes in a separate file, indicated by an asterisk (*) next to the star number. (2 data files).

Determining the most suitable areas for artificial groundwater recharge via an integrated PROMETHEE II-AHP method in GIS environment (case study: Garabaygan Basin, Iran).

PubMed

Nasiri, Hossein; Boloorani, Ali Darvishi; Sabokbar, Hassan Ali Faraji; Jafari, Hamid Reza; Hamzeh, Mohamad; Rafii, Yusef

2013-01-01

Flood spreading is a suitable strategy for controlling and benefiting from floods. Selecting suitable areas for flood spreading and directing the floodwater into permeable formations are amongst the most effective strategies in flood spreading projects. Having combined geographic information systems (GIS) and multi-criteria decision analysis approaches, the present study sought to locate the most suitable areas for flood spreading operation in the Garabaygan Basin of Iran. To this end, the data layers relating to the eight effective factors were prepared in GIS environment. This stage was followed by elimination of the exclusionary areas for flood spreading while determining the potentially suitable ones. Having closely examined the potentially suitable areas using the Preference Ranking Organization Method for Enrichment Evaluations (PROMETHEE) II and analytic hierarchy process (AHP) methods, the land suitability map for flood spreading was produced. The PROMETHEE II and AHP were used for ranking all the alternatives and weighting the criteria involved, respectively. The results of the study showed that most suitable areas for the artificial groundwater recharge are located in Quaternary Q(g) and Q(gsc) geologic units and in geomorphological units of pediment and Alluvial fans with slopes not exceeding 3%. Furthermore, significant correspondence between the produced map and the control areas, where the flood spreading projects were successfully performed, provided further evidence for the acceptable efficiency of the integrated PROMETHEE II-AHP method in locating suitable flood spreading areas.

Astronomical Surveys, Catalogs, Databases, and Archives

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.

2016-06-01

All-sky and large-area astronomical surveys and their cataloged data over the whole range of electromagnetic spectrum are reviewed, from γ-ray to radio, such as Fermi-GLAST and INTEGRAL in γ-ray, ROSAT, XMM and Chandra in X-ray, GALEX in UV, SDSS and several POSS I and II based catalogues (APM, MAPS, USNO, GSC) in optical range, 2MASS in NIR, WISE and AKARI IRC in MIR, IRAS and AKARI FIS in FIR, NVSS and FIRST in radio and many others, as well as most important surveys giving optical images (DSS I and II, SDSS, etc.), proper motions (Tycho, USNO, Gaia), variability (GCVS, NSVS, ASAS, Catalina, Pan-STARRS) and spectroscopic data (FBS, SBS, Case, HQS, HES, SDSS, CALIFA, GAMA). Most important astronomical databases and archives are reviewed as well, including Wide-Field Plate DataBase (WFPDB), ESO, HEASARC, IRSA and MAST archives, CDS SIMBAD, VizieR and Aladin, NED and HyperLEDA extragalactic databases, ADS and astro-ph services. They are powerful sources for many-sided efficient research using Virtual Observatory tools. Using and analysis of Big Data accumulated in astronomy lead to many new discoveries.

Pediatric Glioblastoma Therapies Based on Patient-Derived Stem Cell Resources

DTIC Science & Technology

2013-10-01

stem cell lines have been successfully isolated from adults, in this proposal we aim to isolate and characterize GSC populations from pediatric patients. In the past two years we have successfully derived and cultured eight patient-derived pediatric glioma stem cell lines. In the past year we have continued molecular and phenotypic characterization of these lines. This characterization included analysis of gene expression and patient-specific gene mutations, and also proof-of-concept shRNA screens. In addition we have begun to identify candidate

Improvements Needed in U.S. Special Operations Command Global Battlestaff and Program Support Contract Oversight

DTIC Science & Technology

2013-04-26

and 6-8 books annually. Some deliverables are due “as required.” This is because the mission of the IATF is dependent upon real-world events and...six lines of investigation (4.1.18). Some deliverables do not have specific due dates or schedules because the mission of the IATF is dependent upon...34 This is because the mission of the IATF is dependent upon real-world events and deliverables are linked to dynamic findings from the SOCOM GSC

Joint Diagonalization Applied to the Detection and Discrimination of Unexploded Ordnance

DTIC Science & Technology

2012-08-01

center (Das et al., 1990; Barrow and Nelson, 2001; Bell et al., 2001; Pasion and Oldenburg , 2001; Zhang et al., 2003; Smith and Mor- rison, 2004; Tarokh et...matrix for the complete transmitter/receiver ar- ray by tiling all the Nr × Nt available samples of expression 5: S ¼ GscUlΛ̇lUTl ðGprÞT...L. R., and D. W. Oldenburg , 2001, A discrimination algorithm for UXO using time-domain electromagnetics: Journal of Environmental and Engineering

VINSON/AUTOVON Interface Applique for the Modem, Digital Data, AN/GSC-38

DTIC Science & Technology

1980-11-01

Measurement Indication Result Before Step 6 None Noise and beeping are heard in handset After Step 7 None Noise and beepi ng disappear Condition Measurement...linear range due to the compression used. Lowering the levels below the compression range may give increased linearity, but may cause signal-to- noise ...are encountered where the bit error rate at 16 KB/S results is objectionable audio noise or causes the KY-58 to squelch. On these channels the bit

Defining Genome Project Standards in a New Era of Sequencing (GSC8 Meeting)

ScienceCinema

Chain, Patrick

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego.

Mei-P26 Cooperates with Bam, Bgcn and Sxl to Promote Early Germline Development in the Drosophila Ovary

PubMed Central

Li, Yun; Zhang, Qiao; Carreira-Rosario, Arnaldo; Maines, Jean Z.; McKearin, Dennis M.; Buszczak, Michael

2013-01-01

In the Drosophila female germline, spatially and temporally specific translation of mRNAs governs both stem cell maintenance and the differentiation of their progeny. However, the mechanisms that control and coordinate different modes of translational repression within this lineage remain incompletely understood. Here we present data showing that Mei-P26 associates with Bam, Bgcn and Sxl and nanos mRNA during early cyst development, suggesting that this protein helps to repress the translation of nanos mRNA. Together with recently published studies, these data suggest that Mei-P26 mediates both GSC self-renewal and germline differentiation through distinct modes of translational repression depending on the presence of Bam. PMID:23526974

Nuclear lamina builds tissues from the stem cell niche.

PubMed

Chen, Haiyang; Zheng, Yixian

2014-01-01

Recent studies show that nuclear lamins, the type V intermediate filament proteins, are required for proper building of at least some organs. As the major structural components of the nuclear lamina found underneath the inner nuclear membranes, lamins are ubiquitously expressed in all animal cells. How the broadly expressed lamins support the building of specific tissues is not understood. By studying Drosophila testis, we have uncovered a mechanism by which lamin-B functions in the cyst stem cell (CySC) and its differentiated cyst cell, the cell types known to form the niche/microenvironment for the germline stem cells (GSC) and the developing germ line, to ensure testis organogenesis (1). In this extra view, we discuss some remaining questions and the implications of our findings in the understanding of how the ubiquitous nuclear lamina regulates tissue building in a context-dependent manner.

Senescence from glioma stem cell differentiation promotes tumor growth

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

Ouchi, Rie; Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550; Okabe, Sachiko

Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such asmore » IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.« less

ET-33PLACENTA-DERIVED MESENCHYMAL STEM CELLS AND THEIR SECRETED EXOSOMES INHIBIT THE SELF-RENEWAL AND STEMNESS OF GLIOMA STEM CELLS IN VITRO AND IN VIVO

PubMed Central

Lee, Hae Kyung; Buchris, Efrat; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Poisson, Laila; Brodie, Chaya

2014-01-01

Mesenchymal stromal cells (MSCs) are multipotent stem cells that can be obtained from bone marrow and adipose tissues or from other sources such as placenta and umbilical cord. The latter allow the potential use of universal, allogeneic cell therapy because to reduced antigenicity due to low expression of MHC class II molecules. MSCs can be easily expanded in vitro for therapeutic applications and their safety and therapeutic impact have been demonstrated in various pre-clinical and clinical studies. MSCs have been shown to cross the blood brain barrier and migrate to sites of experimental GBM and can deliver cytotoxic compounds that exert anti-tumor effects. In this study we examined the effects of placenta-derived MSCs and their secreted exosomes on GSCs in vitro and in vivo. Conditioned medium of placenta MSCs or their derived exosomes decreased the self-renewal, stemness markers, Sox2 and Oct4 and the migration of these cells. Similarly, intracranial administration of the MSCs decreased the tumor volume of GSC-derived xenografts and prolonged animal survival. miRNA sequencing analysis of placenta MSC-derived exosomes revealed a set of specific miRNAs that were downregulated in GSCs and that acted as tumor suppressor in these cells. We demonstrated delivery of some of these miRNAs to GSCs following treatments with MSC-derived exosomes. We further demonstrated that MSCs or exosomes that were loaded with exogenous miR-124 delivered high levels of this miRNA into glioma cells as detected by a novel quantitative miRNA reporter. Moreover, administration of placenta MSCs loaded with exogenous miR-124 exerted a strong inhibitory effect on GSC-derived xenograft growth. These results demonstrate that placenta-derived MSCs may have important clinical applications in stem cell-based glioma therapeutics. Moreover, these studies provide a novel approach for the targeted delivery of endogenous and exogenous anti-tumor miRNAs to glioma cells as a miRNA replacement therapy for GBM.

Multipotent adult germ-line stem cells, like other pluripotent stem cells, can be killed by cytotoxic T lymphocytes despite low expression of major histocompatibility complex class I molecules

PubMed Central

Dressel, Ralf; Guan, Kaomei; Nolte, Jessica; Elsner, Leslie; Monecke, Sebastian; Nayernia, Karim; Hasenfuss, Gerd; Engel, Wolfgang

2009-01-01

Background Multipotent adult germ-line stem cells (maGSCs) represent a new pluripotent cell type that can be derived without genetic manipulation from spermatogonial stem cells (SSCs) present in adult testis. Similarly to induced pluripotent stem cells (iPSCs), they could provide a source of cellular grafts for new transplantation therapies of a broad variety of diseases. To test whether these stem cells can be rejected by the recipients, we have analyzed whether maGSCs and iPSCs can become targets for cytotoxic T lymphocytes (CTL) or whether they are protected, as previously proposed for embryonic stem cells (ESCs). Results We have observed that maGSCs can be maintained in prolonged culture with or without leukemia inhibitory factor and/or feeder cells and still retain the capacity to form teratomas in immunodeficient recipients. They were, however, rejected in immunocompetent allogeneic recipients, and the immune response controlled teratoma growth. We analyzed the susceptibility of three maGSC lines to CTL in comparison to ESCs, iPSCs, and F9 teratocarcinoma cells. Major histocompatibility complex (MHC) class I molecules were not detectable by flow cytometry on these stem cell lines, apart from low levels on one maGSC line (maGSC Stra8 SSC5). However, using a quantitative real time PCR analysis H2K and B2m transcripts were detected in all pluripotent stem cell lines. All pluripotent stem cell lines were killed in a peptide-dependent manner by activated CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the SIINFEKL peptide. Conclusion Pluripotent stem cells, including maGSCs, ESCs, and iPSCs can become targets for CTLs, even if the expression level of MHC class I molecules is below the detection limit of flow cytometry. Thus they are not protected against CTL-mediated cytotoxicity. Therefore, pluripotent cells might be rejected after transplantation by this mechanism if specific antigens are presented and if specific activated CTLs are present. Our results show that the adaptive immune system has in principle the capacity to kill pluripotent and teratoma forming stem cells. This finding might help to develop new strategies to increase the safety of future transplantations of in vitro differentiated cells by exploiting a selective immune response against contaminating undifferentiated cells. Reviewers This article was reviewed by Bhagirath Singh, Etienne Joly and Lutz Walter. PMID:19715575

Building the oceanic crust: Insights on volcanic emplacement processes at the hotspot-influenced Galápagos Spreading Center, 92°W

NASA Astrophysics Data System (ADS)

McClinton, J. T.; White, S. M.; Colman, A.; Sinton, J. M.

2011-12-01

The Galápagos Spreading Center (GSC) displays a range of axial morphology due to increased magma supply from the adjacent Galápagos mantle plume. Over 30 years of scientific exploration has also documented the associated variations in volcanic terrain, crustal thickness, and geochemistry of erupted basalts, but until recently the fine-scale ("lava flow scale") volcanic features of the GSC had not been investigated. Using the Alvin submersible and aided by near-bottom photographic surveys by TowCam and sub-meter-scale sonar surveys by AUV Sentry, we mapped and sampled 12 individual eruptive units covering ~16km2 of seafloor on the ridge axis of the GSC at 92°W. Variations in AUV Sentry bathymetry and DSL-120A backscatter enabled us to characterize the fine-scale surface morphology within each eruptive unit. Lava flow morphologies within each unit were identified using a neuro-fuzzy classifier which assigns pixels as pillows, lobates, sheets, or fissures by using attributes derived from high-resolution sonar bathymetry and backscatter (McClinton et al., submitted PE&RS). An accuracy assessment indicates approximately 90% agreement between the lava morphology map and an independent set of visual observations. The result of this classification effort is that we are able to quantitatively examine the spatial distribution of lava flow morphology as it relates to the emplacement of lava flows within each eruptive unit at a mid-ocean ridge. Preliminary analyses show that a large, segment-centered volcanic cone which straddles the axial summit graben (the "Empanada") is constructed mostly of pillow lavas, while volcanism in the rifted center of the cone consists of lobate and sheet flows. Conversely, along the rest of the segment, on-axis eruptions consist mainly of pillow lava with most sheet and lobate flows found outside of a small axial summit graben. At least some of these sheet flows are fed by lava channels, suggesting emplacement over distances up to 1km, while pillow lava within the summit graben form low mounds; we speculate that eruption effusion rates decreased over the eruptive episode, producing changes in lava morphology within the larger eruptive units. Many axial mounds are also cut by the graben faults. The relatively young appearance of the lava surfaces at 92°W argues for a close relationship between volcanism and graben faulting on this part of the ridge.

Spline-Screw Multiple-Rotation Mechanism

NASA Technical Reports Server (NTRS)

Vranish, John M.

1994-01-01

Mechanism functions like combined robotic gripper and nut runner. Spline-screw multiple-rotation mechanism related to spline-screw payload-fastening system described in (GSC-13454). Incorporated as subsystem in alternative version of system. Mechanism functions like combination of robotic gripper and nut runner; provides both secure grip and rotary actuation of other parts of system. Used in system in which no need to make or break electrical connections to payload during robotic installation or removal of payload. More complicated version needed to make and break electrical connections. Mechanism mounted in payload.

Public health assessment for Garden State Cleaners, Cerclis No. NJD053280160 and South Jersey Clothing Company, Minotola, Atlantic County, New Jersey, Region 2. Cerclis No. NJD980766828. addendum. Final report

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

NONE

1995-04-21

The Garden State Cleaners (GSC) and South Jersey Clothing Company (SJCC) sites are located in Buena Borough, Atlantic County, New Jersey. Completed human exposure pathway existed in the past at the site and were associated with groundwater, and ambient air (SJCC). Potential exposure pathways are associated with groundwater and on site soils (SJCC). Based upon the likelihood of past exposure, ATSDR and NJDOH consider this site to have posed a public health hazard.

Gateways to the FANTOM5 promoter level mammalian expression atlas

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

Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). In conclusion, this resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas.

Gateways to the FANTOM5 promoter level mammalian expression atlas

DOE PAGES

Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi; ...

2015-01-05

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). In conclusion, this resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas.

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

Samec, R. G.; Melton, R. A.; Figg, E. R.

GSC 3355 0394 has an EB-type light curve, which is dominated by hot and cool spot activities. It displays night-to-night variations in light-curve shapes. The period study yields six new times of minimum light and the first precision ephemeris, HJD T{sub min}I = 2, 454, 408.9547 {+-} 0.0017 + 0.4621603 {+-} 0.0000008d*E. VR{sub c}I{sub c} standard magnitudes are presented. BVRI Wilson synthetic light-curve solutions are calculated for both a Mode 4 (V1010 Oph-type, semidetached, more massive component filling its Roche lobe) configuration and a Mode 3, contact configuration (fill-out 100% or critical contact). The critical contact is the lowest residualmore » solution. Four major spot regions are needed to model this binary, at least one is evidently a stream spot.« less

Vent Complexes above Dolerite Sills in Phanerozoic LIPs: Implications for Proterozoic LIPs and IOCG Deposits

NASA Astrophysics Data System (ADS)

Ernst, R. E.; Bleeker, W.; Svensen, H.; Planke, S.; Polozov, A. G.

2009-05-01

New insights into the origin of IOCG (iron oxide copper gold) deposits [e.g., 1, 2, 3] follow from recent studies of Phanerozoic Large Igneous Provinces (LIPs). Detailed seismic studies of the 62-55 Ma North Atlantic Igneous Province and complementary studies in the 183 Ma Karoo and 250 Ma Siberian LIPs reveal thousands of hydrothermal vent complexes (HVCs). Up to 5-10 km across at the paleosurface, these vents connect to underlying dolerite sills at paleodepths of up to 8 km [4, 5, 6, 7]. They originate from explosive release of gases generated when thick sills (>50 m) are emplaced into volatile-rich but low-permeability sedimentary strata. HVCs are phreatomagmatic in origin. Their architecture, economic potential for IOCG-type deposits, and effects on climate strongly depend on the type of host rocks (black shales at Karoo and evaporites at Siberian LIPs) and its fluid (brines) saturation at the time of emplacement. About 250 HVCs associated with the Siberian LIP are mineralized having magnetite in the matrix. Some are being mined for Fe (Korshunovskoe and Rudnogorskoe), but their economic potential for copper and gold mineralization is understudied. These observations from the Phanerozoic LIP record suggest that HVCs should also be an essential component of sill provinces associated with Proterozoic LIPs, with a potential for causing major climatic shifts and IOCG-type deposits, particularly if the host sediments include substantial evaporites. Two examples are discussed here. The 725 Ma Franklin LIP covers 1.1 Mkm2 in northern Canada [8]; in the Minto Inlier of Victoria Island, this event comprises volcanics, sills, and breccia pipes [9, 10]. The breccia pipes appear identical to HVCs and, furthermore, the presence of evaporites in the host sediments of the Shaler Supergroup suggests (based on the Siberian trap example) the potential for IOCG-type mineralization. Could 1.59 Ga sills, as exemplified by the exposed Western Channel Diabase sills on the eastern side of Great Bear Lake [11], be the cause of both the Wernecke Breccias of the Yukon (with their hematite, Cu, Co, U and Au mineralization) and the Olympic Dam giant IOCG deposit of the Gawler craton of Australia, which was probably an adjacent block at this time [12, 11]? A dramatic expansion of new targets for IOCGs potentially could be achieved via a systematic survey of sill provinces associated with Proterozoic and Paleozoic LIPs from around the world, with a special focus on those in which the host sediments are evaporate-rich, with the goal of identifying mineralized HVCs. [1] Hitzman, 2000, In: Porter (ed.) v.1; PGC Publishing; [2] Williams et al., 2005, Econ. Geol; [3] Corriveau, 2007, GAC Min. Dep. Div. Spec. Pub 5; [4] Jamtveit et al., 2004, In: Geol. Soc. London, Spec. Publ. 234; [5] Planke et al., 2005, In: Dore & Vining (eds) Geol. Soc. London; [6] Svensen et al., 2006, J. Geol. Soc. London; [7] Svensen et al., 2008, EPSL; [8] Buchan & Ernst, 2004 GSC. Map 2022A; [9] Jefferson et al., 1994, GSC. OF 2789; [10] Rainbird, 1998, GSC OF File 3671; [11] Hamilton & Buchan 2007, GSA Ann. Mtg ; [12] Thorkelson et al., 2001, Prec. Res.

Chromatographic properties PLOT multicapillary columns.

PubMed

Nikolaeva, O A; Patrushev, Y V; Sidelnikov, V N

2017-03-10

Multicapillary columns (MCCs) for gas chromatography make it possible to perform high-speed analysis of the mixtures of gaseous and volatile substances at a relatively large amount of the loaded sample. The study was performed using PLOT MCCs for gas-solid chromatography (GSC) with different stationary phases (SP) based on alumina, silica and poly-(1-trimethylsilyl-1-propyne) (PTMSP) polymer as well as porous polymers divinylbenzene-styrene (DVB-St), divinylbenzene-vinylimidazole (DVB-VIm) and divinylbenzene-ethylene glycol dimethacrylate (DVB-EGD). These MCCs have the efficiency of 4000-10000 theoretical plates per meter (TP/m) and at a column length of 25-30cm can separate within 10-20s multicomponent mixtures of substances belonging to different classes of chemical compounds. The sample amount not overloading the column is 0.03-1μg and depends on the features of a porous layer. Examples of separations on some of the studied columns are considered. Copyright © 2017 Elsevier B.V. All rights reserved.

Dissection and staining of Drosophila larval ovaries.

PubMed

Maimon, Iris; Gilboa, Lilach

2011-05-13

Many organs depend on stem cells for their development during embryogenesis and for maintenance or repair during adult life. Understanding how stem cells form, and how they interact with their environment is therefore crucial for understanding development, homeostasis and disease. The ovary of the fruit fly Drosophila melanogaster has served as an influential model for the interaction of germ line stem cells (GSCs) with their somatic support cells (niche) (1, 2). The known location of the niche and the GSCs, coupled to the ability to genetically manipulate them, has allowed researchers to elucidate a variety of interactions between stem cells and their niches (3-12). Despite the wealth of information about mechanisms controlling GSC maintenance and differentiation, relatively little is known about how GSCs and their somatic niches form during development. About 18 somatic niches, whose cellular components include terminal filament and cap cells (Figure 1), form during the third larval instar (13-17). GSCs originate from primordial germ cells (PGCs). PGCs proliferate at early larval stages, but following the formation of the niche a subgroup of PGCs becomes GSCs (7, 16, 18, 19). Together, the somatic niche cells and the GSCs make a functional unit that produces eggs throughout the lifetime of the organism. Many questions regarding the formation of the GSC unit remain unanswered. Processes such as coordination between precursor cells for niches and stem cell precursors, or the generation of asymmetry within PGCs as they become GSCs, can best be studied in the larva. However, a methodical study of larval ovary development is physically challenging. First, larval ovaries are small. Even at late larval stages they are only 100μm across. In addition, the ovaries are transparent and are embedded in a white fat body. Here we describe a step-by-step protocol for isolating ovaries from late third instar (LL3) Drosophila larvae, followed by staining with fluorescent antibodies. We offer some technical solutions to problems such as locating the ovaries, staining and washing tissues that do not sink, and making sure that antibodies penetrate into the tissue. This protocol can be applied to earlier larval stages and to larval testes as well.

CB-02MiRNA EXPRESSION PROFILES OF GLIOMA STEM CELLS AND THEIR ASSOCIATION WITH THE MESENCHYMAL TRANSFORMATION OF THESE CELLS

PubMed Central

Bier, Ariel; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Lee, Hae Kyung; Rand, Daniel; Yalon, Michal; Toren, Amos; Poisson, Laila; Brodie, Chaya

2014-01-01

Glioblastoma, are characterized by increased infiltration into the surrounding brain tissue, resistance to therapies, and poor prognosis. A major pathway that contributes to these characteristics is the mesenchymal phenotype of these tumors. A small subpopulation of cancer stem cells (GSCs) have been implicated in the enhanced infiltration, radio-resistance and tumor recurrence. GSCs share some similarities with neural stem cells (NSCs) but exhibit deregulated differentiation ability and enhanced oncogenic potential. Recent studies documented miRNAs as important regulators of GSC functions and of the malignant and stemness features of these cells. In this study we performed miRNA and mRNA integrated analysis of GSCs compared to human NSCs and mesenchymal stromal cells (MSCs) to identify significant miRNA-mRNA signatures associated with the mesenchymal signature of GSCs, using miRNA and mRNA microarray analysis. The comparison of GSCs and NSCs identified 79 miRNAs that were upregulated in GSCs and 21 miRNAs that were increased in MSCs. Twenty six miRNAs were downregulated in GSCs compared to NSCs and 21 miRNAs from this group were further downregulated in MSCs. The comparison of mRNA expression of GSCs and NSCs identified gene clusters associated with glioma cell invasiveness, axonal guidance signaling and TGF-b signaling. miR-504 is one of the miRNAs that was significantly downregulated in GSCs compared to NSCs. The expression of miR-504 was also decreased in mesenchymal GBM and highly increased in the G-CIMP subset of GBM. miR-504 promoted the neural differentiation of GSC, inhibited their self-renewal, migration and the mesenchymal signature of these cells, by downregulating CD44, BCAN, ZRB1 and ZEB2. In conclusion, these results reveal novel miRNAs and potential target networks that play a role in the oncogenic potential and stemness of GSCs and in their mesenchymal transformation and may lead to the identification of therapeutic targets for the eradication of GSCs and the treatment of GBM.

Coordinated Regulation of Niche and Stem Cell Precursors by Hormonal Signaling

PubMed Central

Gancz, Dana; Lengil, Tamar; Gilboa, Lilach

2011-01-01

Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells (GSCs), and somatic niche precursors develop within the larval ovary. Together they form the 16–20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis. PMID:22131903

USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance.

PubMed

Lee, Jin-Ku; Chang, Nakho; Yoon, Yeup; Yang, Heekyoung; Cho, Heejin; Kim, Eunhee; Shin, Yongjae; Kang, Wonyoung; Oh, Young Taek; Mun, Gyeong In; Joo, Kyeung Min; Nam, Do-Hyun; Lee, Jeongwu

2016-01-01

Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. USP1 was highly expressed in gliomas relative to normal brain tissues and more preferentially in GSC enrichment marker (CD133 or CD15) positive cells. USP1 positively regulated the protein stability of the ID1 and CHEK1, critical regulators of DNA damage response and stem cell maintenance. Targeting USP1 by RNA interference or treatment with a chemical USP1 inhibitor attenuated clonogenic growth and survival of GSCs and enhanced radiosensitivity of GBM cells. Finally, USP1 inhibition alone or in combination with radiation significantly prolonged the survival of tumor-bearing mice. USP1-mediated protein stabilization promotes GSC maintenance and treatment resistance, thereby providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

VizieR Online Data Catalog: GSC04778-00152 photometry and spectroscopy (Tuvikene+, 2008)

NASA Astrophysics Data System (ADS)

Tuvikene, T.; Sterken, C.; Eenmae, T.; Hinojosa-Goni, R.; Brogt, E.; Longa Pena, P.; Liimets, T.; Ahumada, M.; Troncoso, P.; Vogt, N.

2012-04-01

CCD photometry of GSC04778-00152 was carried out on 54 nights during 9 observing runs. In January 2006 the observations were made with the 41-cm Meade telescope at Observatorio Cerro Armazones (OCA), Chile, using an SBIG STL-6303E CCD camera (3072x2048 pixels, FOV 23.0'x15.4') and Johnson V filter. On 3 nights in December 2006 and on 2 nights in October 2007 we used the 2.4-m Hiltner telescope at the MDM Observatory, Arizona, USA, equipped with the 8kx8k Mosaic imager (FOV 23.6'x23.6'). In December 2006 and January 2007, we also used the 41-cm Meade telescope at OCA, using an SBIG ST-7XME CCD camera (FOV 5.9'x3.9') with no filter. Figure 3 shows all OCA light curves obtained with this configuration. At Tartu Observatory the observations were carried out in December 2006 and January 2007, using the 60-cm telescope with a SpectraSource Instruments HPC-1 camera (1024x1024 pixels, FOV 11.2'x11.2') and V filter. >From January to March 2007 the system was observed using the 1.0-m telescope at SAAO, Sutherland, South Africa with an STE4 CCD camera (1024x1024 pixels, FOV 5.3'x5.3') and UBVRI filters. Spectroscopic observations were carried out at the Tartu Observatory, Estonia, using the 1.5-m telescope with the Cassegrain spectrograph ASP-32 and an Andor Newton CCD camera. (3 data files).

Annotations in Refseq (GSC8 Meeting)

ScienceCinema

Tatusova, Tatiana

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Tatiana Tatusova of NCBI discusses "Annotations in Refseq" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Towards a Consensus Annotation System (GSC8 Meeting)

ScienceCinema

White, Owen

2018-02-01

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Towards Consensus Annotation at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways.

PubMed

Bijangi-Vishehsaraei, Khadijeh; Reza Saadatzadeh, M; Wang, Haiyan; Nguyen, Angie; Kamocka, Malgorzata M; Cai, Wenjing; Cohen-Gadol, Aaron A; Halum, Stacey L; Sarkaria, Jann N; Pollok, Karen E; Safa, Ahmad R

2017-12-01

OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.

Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

PubMed Central

Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

2012-01-01

The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches. PMID:23185495

VizieR Online Data Catalog: ASC Gaia Attitude Star Catalog (Smart, 2015)

NASA Astrophysics Data System (ADS)

Smart, R. L.

2015-04-01

The ASC is a compilation produced for the Gaia mission. We have combined data from the following catalogs or datasets to produce a homogenous list of positions, proper motions, photometry in a blue and red band and estimates of the magnitudes in the Gaia G and G_RVS bands: Tycho2, UCAC4, Hipparcos, PPMXL, GSC2.3 and Sky2000. Originally ASC sources were selected from the Initial Gaia Source List (IGSL, I/324). However, here we produce a cleaner catalog starting from the bright source catalogs and using the following criteria: 1) The candidate must be in the Tycho2, UCAC4, Hipparcos or Sky2000 catalog. 2) The Gaia G magnitude must be brighter than 13.4. 3) The star must be isolated from other objects of similar magnitudes 4) The object must not be in the Washington Double Star catalog 5) If a healpix 6th region has more than 1000 objects the magnitude limit is reduced to reduce the number of objects in that region. Since the ASC was produced independently from the IGSL using different procedures there is not a direct 1 to 1 match between ASC and IGSL entries. We have matched the ASC to the IGSL and found that 9 out of the 8 million entries do not have a clear match. Since there may still remain ambiguous matches in the 8 million matched objects, we decided to assign the sourceIDs of the IGSL with the adjustment that the runningnumber is equal to the IGSL runningnumber + 320000. Included Catalogs: Tycho2, UCAC4, Sky2000, HIPPARCOS for candidates and the PPMXL, GSC2.3 were used to calculating magnitudes. (2 data files).

Genetic analysis of 430 Chinese Cynodon dactylon accessions using sequence-related amplified polymorphism markers.

PubMed

Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

2014-10-21

Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260-1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53-0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars.

[The opportunity to use combined stem cells transplantation for haemopoesis activation in the old and mature laboratory animals under the conditions of ionizing radiation].

PubMed

Grebnev, D Iu; Maklakova, I Iu; Iastrebov, A P

2014-01-01

The objective of this work was to study the influence of combined transplantation of stem cells (multypotent mesenchimal stromal and haemopoetic stem cells) on the haemopoesis of old and mature laboratory animals under the condition of ionizing radiation. The result of the experiment shows that under physiological conditions the combined transplantation brings the erithropoesis activation, under the ionizing radiation conditions it brings the erythroid and granulocytopoesis activation. Moreover the combined MMSC and HSC transplantation gives cytoprotective action on the myeloid tissue due to decrease of cyto genically changed cells in the mature animals under the condition of ionizing radiation, but in the old animals this effect can be seen even under physiological condition. Combined transplantation of MMSC and GSC can be used in the mature and old laboratory animals under the conditions of ionising radiation for the haemopoesis activation.

The Genomes OnLine Database (GOLD) v.5: a metadata management system based on a four level (meta)genome project classification

PubMed Central

Reddy, T.B.K.; Thomas, Alex D.; Stamatis, Dimitri; Bertsch, Jon; Isbandi, Michelle; Jansson, Jakob; Mallajosyula, Jyothi; Pagani, Ioanna; Lobos, Elizabeth A.; Kyrpides, Nikos C.

2015-01-01

The Genomes OnLine Database (GOLD; http://www.genomesonline.org) is a comprehensive online resource to catalog and monitor genetic studies worldwide. GOLD provides up-to-date status on complete and ongoing sequencing projects along with a broad array of curated metadata. Here we report version 5 (v.5) of the database. The newly designed database schema and web user interface supports several new features including the implementation of a four level (meta)genome project classification system and a simplified intuitive web interface to access reports and launch search tools. The database currently hosts information for about 19 200 studies, 56 000 Biosamples, 56 000 sequencing projects and 39 400 analysis projects. More than just a catalog of worldwide genome projects, GOLD is a manually curated, quality-controlled metadata warehouse. The problems encountered in integrating disparate and varying quality data into GOLD are briefly highlighted. GOLD fully supports and follows the Genomic Standards Consortium (GSC) Minimum Information standards. PMID:25348402

Systems Biology Knowledgebase (GSC8 Meeting)

ScienceCinema

Cottingham, Robert W.

2018-01-04

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Robert W. Cottingham of Oak Ridge National Laboratory discusses the DOE Knowledge Base at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Acoustical Applications of the HHT Method

NASA Technical Reports Server (NTRS)

Huang, Norden E.

2003-01-01

A document discusses applications of a method based on the Huang-Hilbert transform (HHT). The method was described, without the HHT name, in Analyzing Time Series Using EMD and Hilbert Spectra (GSC-13817), NASA Tech Briefs, Vol. 24, No. 10 (October 2000), page 63. To recapitulate: The method is especially suitable for analyzing time-series data that represent nonstationary and nonlinear physical phenomena. The method involves the empirical mode decomposition (EMD), in which a complicated signal is decomposed into a finite number of functions, called intrinsic mode functions (IMFs), that admit well-behaved Hilbert transforms. The HHT consists of the combination of EMD and Hilbert spectral analysis.

Gene Calling Standards (GSC8 Meeting)

ScienceCinema

Kyrpides, Nikos

2018-04-27

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Nikos Kyrpides of the DOE Joint Genome Institute discusses gene calling standards at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Terragenome: International Soil Metagenome Sequencing Consortium (GSC8 Meeting)

ScienceCinema

Jansson, Janet

2018-01-04

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Janet Jansson of the Lawrence Berkeley National Laboratory discusses the Terragenome Initiative at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Enhancing the LVRT Capability of PMSG-Based Wind Turbines Based on R-SFCL

NASA Astrophysics Data System (ADS)

Xu, Lin; Lin, Ruixing; Ding, Lijie; Huang, Chunjun

2018-03-01

A novel low voltage ride-through (LVRT) scheme for PMSG-based wind turbines based on the Resistor Superconducting Fault Current Limiter (R-SFCL) is proposed in this paper. The LVRT scheme is mainly formed by R-SFCL in series between the transformer and the Grid Side Converter (GSC), and basic modelling has been discussed in detail. The proposed LVRT scheme is implemented to interact with PMSG model in PSCAD/EMTDC under three phase short circuit fault condition, which proves that the proposed scheme based on R-SFCL can improve the transient performance and LVRT capability to consolidate grid connection with wind turbines.

The Biocurator Society (GSC8 Meeting)

ScienceCinema

Gaudet, Pascal

2018-01-10

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Pascal Gaudet of Northwestern University talks about "The Biocurator Society" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 11, 2009.

Toxicological Assessment of ISS Air Quality: June - September 2013 (Increment 36)

NASA Technical Reports Server (NTRS)

Meyers, Valerie

2014-01-01

Fourteen mini grab sample containers (msGSCs) were collected on ISS between June and September 2013 and were returned on 34S; however, the ATV-4 first ingress mGSC did not contain sufficient sample to report results (initial sample pressure = 1.2 psia). Of the remaining 13 mGSCs, 12 were collected as routine monthly samples in the Russian Service Module (SM), US Laboratory (Lab), and either the Japanese Pressurized Module (JPM) or the Columbus module (Col), and 1 was collected during HTV-4 first ingress. A summary of the analytical results from the 13 valid mGSCs is shown.

Toxicological Assessment of ISS Air Quality: Contingency Sampling - February 2013

NASA Technical Reports Server (NTRS)

Meyers, Valerie

2013-01-01

Two grab sample containers (GSCs) were collected by crew members onboard ISS in response to a vinegar-like odor in the US Lab. On February 5, the first sample was collected approximately 1 hour after the odor was noted by the crew in the forward portion of the Lab. The second sample was collected on February 22 when a similar odor was noted and localized to the end ports of the microgravity science glovebox (MSG). The crewmember removed a glove from the MSG and collected the GSC inside the glovebox volume. Both samples were returned on SpaceX-2 for ground analysis.

2008 Joint United States-Canadian program to explore the limits of the Extended Continental Shelf aboard the U.S. Coast Guard cutter Healy--Cruise HLY0806

USGS Publications Warehouse

Childs, Jonathan R.; Triezenberg, Peter J.; Danforth, William W.

2012-01-01

In September 2008, the U.S. Geological Survey (USGS), in cooperation with Natural Resources Canada, Geological Survey of Canada (GSC), conducted bathymetric and geophysical surveys in the Arctic Beaufort Sea aboard the U.S. Coast Guard cutter USCGC Healy. The principal objective of this mission to the high Arctic was to acquire data in support of delineation of the outer limits of the U.S. and Canadian Extended Continental Shelf (ECS) in the Arctic Ocean in accordance with the provisions of Article 76 of the Law of the Sea Convention. The Healy was accompanied by the Canadian Coast Guard icebreaker Louis S. St- Laurent. The science parties on the two vessels consisted principally of staff from the USGS (Healy), and the GSC and the Canadian Hydrographic Service (Louis). The crew included marine mammal and Native-community observers, ice observers, and biologists conducting research of opportunity in the Arctic Ocean. The joint survey proved an unqualified success. The Healy collected 5,528 km of swath (multibeam) bathymetry (38,806 km2) and CHIRP subbottom profile data, with accompanying marine gravity measurements. The Louis acquired 2,817 km of multichannel seismic (airgun) deep-penetration reflection-profile data along 12 continuous lines, as well as 35 sonobuoy refraction stations and accompanying single-beam bathymetry. The coordinated efforts of the two vessels resulted in seismic-reflection profile data of much higher quality and continuity than if the data had been acquired with a single vessel alone. Equipment failure rate of the seismic equipment gear aboard the Louis was greatly improved with the advantage of having a leading icebreaker. When ice conditions proved too severe to deploy the seismic system, the Louis led the Healy, resulting in much improved quality of the swath bathymetry and CHIRP sub-bottom data in comparison with data collected by the Healy in the lead or working alone. Ancillary science objectives, including ice observations, deployment of ice-monitoring buoys and water-column sampling for biologic (phytoplankton) studies, were also successfully accomplished.

Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.

PubMed

Hinnant, Taylor D; Alvarez, Arturo A; Ables, Elizabeth T

2017-09-01

Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Standards and the INSDC: Submission of MIGS, MIMS, MIENS (GSC8 Meeting)

ScienceCinema

Mizrachi, Ilene

2017-12-21

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding. Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Ilene Mizrachi of the NCBI talks about submission of MIGS/MIMS/MIENS information at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.

Weather Information Processing

NASA Technical Reports Server (NTRS)

1991-01-01

Science Communications International (SCI), formerly General Science Corporation, has developed several commercial products based upon experience acquired as a NASA Contractor. Among them are METPRO, a meteorological data acquisition and processing system, which has been widely used, RISKPRO, an environmental assessment system, and MAPPRO, a geographic information system. METPRO software is used to collect weather data from satellites, ground-based observation systems and radio weather broadcasts to generate weather maps, enabling potential disaster areas to receive advance warning. GSC's initial work for NASA Goddard Space Flight Center resulted in METPAK, a weather satellite data analysis system. METPAK led to the commercial METPRO system. The company also provides data to other government agencies, U.S. embassies and foreign countries.

Oceanic Communities in a Changing Planet - The Tara Oceans Project (GSC8 Meeting)

ScienceCinema

Raes, Jeroen

2018-01-10

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Jeroen Raes of the University of Brussels discusses the Tara-Oceans expedition at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Terragenome: International Soil Metagenome Sequencing Consortium (GSC8 Meeting)

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

Jansson, Janet

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Janet Jansson of the Lawrence Berkeley National Laboratory discusses the Terragenome Initiative at the Genomic Standards Consortium's 8th meeting at the DOE JGI inmore » Walnut Creek, CA on Sept. 9, 2009.« less

Glioblastoma stem cell differentiation into endothelial cells evidenced through live-cell imaging.

PubMed

Mei, Xin; Chen, Yin-Sheng; Chen, Fu-Rong; Xi, Shao-Yan; Chen, Zhong-Ping

2017-08-01

Glioblastoma cell-initiated vascularization is an alternative angiogenesis called vasculogenic mimicry. However, current knowledge on the mechanism of de novo vessel formation from glioblastoma stem cells (GSCs) is limited. Sixty-four glioblastoma samples from patients and 10 fluorescent glioma xenograft samples were examined by immunofluorescence staining for endothelial marker (CD34 and CD31) and glial cell marker (glial fibrillary acidic protein [GFAP]) expression. GSCs were then isolated from human glioblastoma tissue and CD133+/Sox2+ red fluorescent protein-containing (RFP)-GSC-1 cells were established. The ability of these cells to form vascular structures was examined by live-cell imaging of 3D cultures. CD34-GFAP or CD31-GFAP coexpressing glioblastoma-derived endothelial cells (GDEC) were found in 30 of 64 (46.9%) of clinical glioblastoma samples. In those 30 samples, GDEC were found to form vessel structures in 21 (70%) samples. Among 21 samples with GDEC vessels, the CD34+ GDEC vessels and CD31+ GDEC vessels accounted for about 14.16% and 18.08% of total vessels, respectively. In the xenograft samples, CD34+ GDEC were found in 7 out of 10 mice, and 4 out of 7 mice had CD34+ GDEC vessels. CD31+ GDEC were also found in 7 mice, and 4 mice had CD31+ GDEC vessels (10 mice in total). Through live-cell imaging, we observed gradual CD34 expression when cultured with vascular endothelial growth factor in some glioma cells, and a dynamic increase in endothelial marker expression in RFP-GSC-1 in vitro was recorded. Cells expressed CD34 (9.46%) after 6 hours in culture. The results demonstrated that GSCs may differentiate into endothelial cells and promote angiogenesis in glioblastomas. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Dedifferentiation of Glioma Cells to Glioma Stem-like Cells By Therapeutic Stress-induced HIF Signaling in the Recurrent GBM Model.

PubMed

Lee, Gina; Auffinger, Brenda; Guo, Donna; Hasan, Tanwir; Deheeger, Marc; Tobias, Alex L; Kim, Jeong Yeon; Atashi, Fatemeh; Zhang, Lingjiao; Lesniak, Maciej S; James, C David; Ahmed, Atique U

2016-12-01

Increasing evidence exposes a subpopulation of cancer cells, known as cancer stem cells (CSCs), to be critical for the progression of several human malignancies, including glioblastoma multiforme. CSCs are highly tumorigenic, capable of self-renewal, and resistant to conventional therapies, and thus considered to be one of the key contributors to disease recurrence. To elucidate the poorly understood evolutionary path of tumor recurrence and the role of CSCs in this process, we developed patient-derived xenograft glioblastoma recurrent models induced by anti-glioma chemotherapy, temozolomide. In this model, we observed a significant phenotypic shift towards an undifferentiated population. We confirmed these findings in vitro as sorted CD133-negative populations cultured in differentiation-forcing media were found to acquire CD133 expression following chemotherapy treatment. To investigate this phenotypic switch at the single-cell level, glioma stem cell (GSC)-specific promoter-based reporter systems were engineered to track changes in the GSC population in real time. We observed the active phenotypic and functional switch of single non-stem glioma cells to a stem-like state and that temozolomide therapy significantly increased the rate of single-cell conversions. Importantly, we showed the therapy-induced hypoxia-inducible factors (HIF) 1α and HIF2α play key roles in allowing non-stem glioma cells to acquire stem-like traits, as the expression of both HIFs increase upon temozolomide therapy and knockdown of HIFs expression inhibits the interconversion between non-stem glioma cells and GSCs post-therapy. On the basis of our results, we propose that anti-glioma chemotherapy promotes the accumulation of HIFs in the glioblastoma multiforme cells that induces the formation of therapy-resistant GSCs responsible for recurrence. Mol Cancer Ther; 15(12); 3064-76. ©2016 AACR. ©2016 American Association for Cancer Research.

VERY LOW MASS STELLAR AND SUBSTELLAR COMPANIONS TO SOLAR-LIKE STARS FROM MARVELS. V. A LOW ECCENTRICITY BROWN DWARF FROM THE DRIEST PART OF THE DESERT, MARVELS-6b

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

De Lee, Nathan; Stassun, Keivan G.; Cargile, Phillip

2013-06-15

We describe the discovery of a likely brown dwarf (BD) companion with a minimum mass of 31.7 {+-} 2.0 M{sub Jup} to GSC 03546-01452 from the MARVELS radial velocity survey, which we designate as MARVELS-6b. For reasonable priors, our analysis gives a probability of 72% that MARVELS-6b has a mass below the hydrogen-burning limit of 0.072 M{sub Sun }, and thus it is a high-confidence BD companion. It has a moderately long orbital period of 47.8929{sup +0.0063}{sub -0.0062} days with a low eccentricity of 0.1442{sup +0.0078}{sub -0.0073}, and a semi-amplitude of 1644{sup +12}{sub -13} m s{sup -1}. Moderate resolution spectroscopymore » of the host star has determined the following parameters: T{sub eff} = 5598 {+-} 63, log g = 4.44 {+-} 0.17, and [Fe/H] = +0.40 {+-} 0.09. Based upon these measurements, GSC 03546-01452 has a probable mass and radius of M{sub *} = 1.11 {+-} 0.11 M{sub Sun} and R{sub *} = 1.06 {+-} 0.23 R{sub Sun} with an age consistent with less than {approx}6 Gyr at a distance of 219 {+-} 21 pc from the Sun. Although MARVELS-6b is not observed to transit, we cannot definitively rule out a transiting configuration based on our observations. There is a visual companion detected with Lucky Imaging at 7.''7 from the host star, but our analysis shows that it is not bound to this system. The minimum mass of MARVELS-6b exists at the minimum of the mass functions for both stars and planets, making this a rare object even compared to other BDs. It also exists in an underdense region in both period/eccentricity and metallicity/eccentricity space.« less

Tactile cues significantly modulate the perception of sweat-induced skin wetness independently of the level of physical skin wetness

PubMed Central

Fournet, Damien; Hodder, Simon; Havenith, George

2015-01-01

Humans sense the wetness of a wet surface through the somatosensory integration of thermal and tactile inputs generated by the interaction between skin and moisture. However, little is known on how wetness is sensed when moisture is produced via sweating. We tested the hypothesis that, in the absence of skin cooling, intermittent tactile cues, as coded by low-threshold skin mechanoreceptors, modulate the perception of sweat-induced skin wetness, independently of the level of physical wetness. Ten males (22 yr old) performed an incremental exercise protocol during two trials designed to induce the same physical skin wetness but to induce lower (TIGHT-FIT) and higher (LOOSE-FIT) wetness perception. In the TIGHT-FIT, a tight-fitting clothing ensemble limited intermittent skin-sweat-clothing tactile interactions. In the LOOSE-FIT, a loose-fitting ensemble allowed free skin-sweat-clothing interactions. Heart rate, core and skin temperature, galvanic skin conductance (GSC), and physical (wbody) and perceived skin wetness were recorded. Exercise-induced sweat production and physical wetness increased significantly [GSC: 3.1 μS, SD 0.3 to 18.8 μS, SD 1.3, P < 0.01; wbody: 0.26 no-dimension units (nd), SD 0.02, to 0.92 nd, SD 0.01, P < 0.01], with no differences between TIGHT-FIT and LOOSE-FIT (P > 0.05). However, the limited intermittent tactile inputs generated by the TIGHT-FIT ensemble reduced significantly whole-body and regional wetness perception (P < 0.01). This reduction was more pronounced when between 40 and 80% of the body was covered in sweat. We conclude that the central integration of intermittent mechanical interactions between skin, sweat, and clothing, as coded by low-threshold skin mechanoreceptors, significantly contributes to the ability to sense sweat-induced skin wetness. PMID:25878153

New disk discovered with VLT/SPHERE around the M star GSC 07396-00759

NASA Astrophysics Data System (ADS)

Sissa, E.; Olofsson, J.; Vigan, A.; Augereau, J. C.; D'Orazi, V.; Desidera, S.; Gratton, R.; Langlois, M.; Rigliaco, E.; Boccaletti, A.; Kral, Q.; Lazzoni, C.; Mesa, D.; Messina, S.; Sezestre, E.; Thébault, P.; Zurlo, A.; Bhowmik, T.; Bonnefoy, M.; Chauvin, G.; Feldt, M.; Hagelberg, J.; Lagrange, A.-M.; Janson, M.; Maire, A.-L.; Ménard, F.; Schlieder, J.; Schmidt, T.; Szulágyi, J.; Stadler, E.; Maurel, D.; Delboulbé, A.; Feautrier, P.; Ramos, J.; Rigal, F.

2018-05-01

Debris disks are usually detected through the infrared excess over the photospheric level of their host star. The most favorable stars for disk detection are those with spectral types between A and K, while the statistics for debris disks detected around low-mass M-type stars is very low, either because they are rare or because they are more difficult to detect. Terrestrial planets, on the other hand, may be common around M-type stars. Here, we report on the discovery of an extended (likely) debris disk around the M-dwarf GSC 07396-00759. The star is a wide companion of the close accreting binary V4046 Sgr. The system probably is a member of the β Pictoris Moving Group. We resolve the disk in scattered light, exploiting high-contrast, high-resolution imagery with the two near-infrared subsystems of the VLT/SPHERE instrument, operating in the Y J bands and the H2H3 doublet. The disk is clearly detected up to 1.5'' ( 110 au) from the star and appears as a ring, with an inclination i 83°, and a peak density position at 70 au. The spatial extension of the disk suggests that the dust dynamics is affected by a strong stellar wind, showing similarities with the AU Mic system that has also been resolved with SPHERE. The images show faint asymmetric structures at the widest separation in the northwest side. We also set an upper limit for the presence of giant planets to 2 MJ. Finally, we note that the 2 resolved disks around M-type stars of 30 such stars observed with SPHERE are viewed close to edge-on, suggesting that a significant population of debris disks around M dwarfs could remain undetected because of an unfavorable orientation. Based on data collected at the European Southern Observatory, Chile (ESO Program 198.C-0298).

Preliminary characterisation of new glass reference materials (GSA-1G, GSC-1G, GSD-1G and GSE-1G) by laser ablation-inductively coupled plasma-mass spectrometry using 193 nm, 213 nm and 266 nm wavelengths

USGS Publications Warehouse

Guillong, M.; Hametner, K.; Reusser, E.; Wilson, S.A.; Gunther, D.

2005-01-01

New glass reference materials GSA-1G, GSC-1G, GSD-1G and GSE-1G have been characterised using a prototype solid state laser ablation system capable of producing wavelengths of 193 nm, 213 nm and 266 nm. This system allowed comparison of the effects of different laser wavelengths under nearly identical ablation and ICP operating conditions. The wavelengths 213 nm and 266 nm were also used at higher energy densities to evaluate the influence of energy density on quantitative analysis. In addition, the glass reference materials were analysed using commercially available 266 nm Nd:YAG and 193 nm ArF excimer lasers. Laser ablation analysis was carried out using both single spot and scanning mode ablation. Using laser ablation ICP-MS, concentrations of fifty-eight elements were determined with external calibration to the NIST SRM 610 glass reference material. Instead of applying the more common internal standardisation procedure, the total concentration of all element oxide concentrations was normalised to 100%. Major element concentrations were compared with those determined by electron microprobe. In addition to NIST SRM 610 for external calibration, USGS BCR-2G was used as a more closely matrix-matched reference material in order to compare the effect of matrix-matched and non matrix-matched calibration on quantitative analysis. The results show that the various laser wavelengths and energy densities applied produced similar results, with the exception of scanning mode ablation at 266 nm without matrix-matched calibration where deviations up to 60% from the average were found. However, results acquired using a scanning mode with a matrix-matched calibration agreed with results obtained by spot analysis. The increased abundance of large particles produced when using a scanning ablation mode with NIST SRM 610, is responsible for elemental fractionation effects caused by incomplete vaporisation of large particles in the ICP.

Genetic Analysis of 430 Chinese Cynodon dactylon Accessions Using Sequence-Related Amplified Polymorphism Markers

PubMed Central

Huang, Chunqiong; Liu, Guodao; Bai, Changjun; Wang, Wenqiang

2014-01-01

Although Cynodon dactylon (C. dactylon) is widely distributed in China, information on its genetic diversity within the germplasm pool is limited. The objective of this study was to reveal the genetic variation and relationships of 430 C. dactylon accessions collected from 22 Chinese provinces using sequence-related amplified polymorphism (SRAP) markers. Fifteen primer pairs were used to amplify specific C. dactylon genomic sequences. A total of 481 SRAP fragments were generated, with fragment sizes ranging from 260–1800 base pairs (bp). Genetic similarity coefficients (GSC) among the 430 accessions averaged 0.72 and ranged from 0.53–0.96. Cluster analysis conducted by two methods, namely the unweighted pair-group method with arithmetic averages (UPGMA) and principle coordinate analysis (PCoA), separated the accessions into eight distinct groups. Our findings verify that Chinese C. dactylon germplasms have rich genetic diversity, which is an excellent basis for C. dactylon breeding for new cultivars. PMID:25338051

In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells.

PubMed

Ishikura, Yukiko; Yabuta, Yukihiro; Ohta, Hiroshi; Hayashi, Katsuhiko; Nakamura, Tomonori; Okamoto, Ikuhiro; Yamamoto, Takuya; Kurimoto, Kazuki; Shirane, Kenjiro; Sasaki, Hiroyuki; Saitou, Mitinori

2016-12-06

The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Validation of the group nuclear safety climate questionnaire.

PubMed

Navarro, M Felisa Latorre; Gracia Lerín, Francisco J; Tomás, Inés; Peiró Silla, José María

2013-09-01

Group safety climate is a leading indicator of safety performance in high reliability organizations. Zohar and Luria (2005) developed a Group Safety Climate scale (ZGSC) and found it to have a single factor. The ZGSC scale was used as a basis in this study with the researchers rewording almost half of the items on this scale, changing the referents from the leader to the group, and trying to validate a two-factor scale. The sample was composed of 566 employees in 50 groups from a Spanish nuclear power plant. Item analysis, reliability, correlations, aggregation indexes and CFA were performed. Results revealed that the construct was shared by each unit, and our reworded Group Safety Climate (GSC) scale showed a one-factor structure and correlated to organizational safety climate, formalized procedures, safety behavior, and time pressure. This validation of the one-factor structure of the Zohar and Luria (2005) scale could strengthen and spread this scale and measure group safety climate more effectively. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

1986 Great Lakes Seismic refraction survey (GLIMPCE): Line A - refraction mode

USGS Publications Warehouse

Morel-a-l'Huissier, Patrick; Karl, John H.; Tréhu, Anne M.; Hajnal, Zoltan; Mereu, Robert F.; Meyer, Robert P.; Sexton, John L.; Ervin, C. Patrick; Green, Alan G.; Hutchinson, Deborah

1990-01-01

In the fall of 1986, the Geological Survey of Canada (GSC), the United States Geological Survey (USGS), two Canadian universities -- University of Western Ontario and University of Saskatchewan, and four American universities -- Northern Illinois University, Southern Illinois University, University of Wisconsin-Madison and University of Wisconsin-Oshkosh participated in a major deep seismic experiment in Lake Superior under the GLIMPCE (Great Lakes International Multidisciplinary Program on Crustal Evolution) umbrella. This Open-File Report presents the seismic sections for line A, which was shot specifically for refraction recording. The main target for study by this line was the Mid-Continent Rift System. All recording stations, 31 in total (26 land stations and 5 OBSs), recorded energy from shots fired every two minutes (333 m spacing) by a tuned airgun array towed by a contracted ship along line A in Lake Superior. These data are the densest such data ever recorded in the continental North America over such distances. It is also unique since coincident seismic reflection and refraction are available.

Genomes OnLine Database (GOLD) v.6: data updates and feature enhancements

PubMed Central

Mukherjee, Supratim; Stamatis, Dimitri; Bertsch, Jon; Ovchinnikova, Galina; Verezemska, Olena; Isbandi, Michelle; Thomas, Alex D.; Ali, Rida; Sharma, Kaushal; Kyrpides, Nikos C.; Reddy, T. B. K.

2017-01-01

The Genomes Online Database (GOLD) (https://gold.jgi.doe.gov) is a manually curated data management system that catalogs sequencing projects with associated metadata from around the world. In the current version of GOLD (v.6), all projects are organized based on a four level classification system in the form of a Study, Organism (for isolates) or Biosample (for environmental samples), Sequencing Project and Analysis Project. Currently, GOLD provides information for 26 117 Studies, 239 100 Organisms, 15 887 Biosamples, 97 212 Sequencing Projects and 78 579 Analysis Projects. These are integrated with over 312 metadata fields from which 58 are controlled vocabularies with 2067 terms. The web interface facilitates submission of a diverse range of Sequencing Projects (such as isolate genome, single-cell genome, metagenome, metatranscriptome) and complex Analysis Projects (such as genome from metagenome, or combined assembly from multiple Sequencing Projects). GOLD provides a seamless interface with the Integrated Microbial Genomes (IMG) system and supports and promotes the Genomic Standards Consortium (GSC) Minimum Information standards. This paper describes the data updates and additional features added during the last two years. PMID:27794040

The Genomes OnLine Database (GOLD) v.5: a metadata management system based on a four level (meta)genome project classification

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

Reddy, Tatiparthi B. K.; Thomas, Alex D.; Stamatis, Dimitri

The Genomes OnLine Database (GOLD; http://www.genomesonline.org) is a comprehensive online resource to catalog and monitor genetic studies worldwide. GOLD provides up-to-date status on complete and ongoing sequencing projects along with a broad array of curated metadata. Within this paper, we report version 5 (v.5) of the database. The newly designed database schema and web user interface supports several new features including the implementation of a four level (meta)genome project classification system and a simplified intuitive web interface to access reports and launch search tools. The database currently hosts information for about 19 200 studies, 56 000 Biosamples, 56 000 sequencingmore » projects and 39 400 analysis projects. More than just a catalog of worldwide genome projects, GOLD is a manually curated, quality-controlled metadata warehouse. The problems encountered in integrating disparate and varying quality data into GOLD are briefly highlighted. Lastly, GOLD fully supports and follows the Genomic Standards Consortium (GSC) Minimum Information standards.« less

Correlation between the luminosity and spin-period changes during outbursts of 12 Be binary pulsars observed by the MAXI/GSC and the Fermi/GBM

NASA Astrophysics Data System (ADS)

Sugizaki, Mutsumi; Mihara, Tatehiro; Nakajima, Motoki; Makishima, Kazuo

2017-12-01

To study observationally the spin-period changes of accreting pulsars caused by the accretion torque, the present work analyzes X-ray light curves of 12 Be binary pulsars obtained by the MAXI Gas-Slit Camera all-sky survey and their pulse periods measured by the Fermi Gamma-ray Burst Monitor pulsar project, both covering more than six years, from 2009 August to 2016 March. The 12 objects were selected because they are accompanied by clear optical identification and accurate measurements of surface magnetic fields. The luminosity L and the spin-frequency derivatives \\dot{ν}, measured during large outbursts with L ≳ 1 × 1037 erg s-1, were found to follow approximately the theoretical relations in the accretion torque models, represented by \\dot{ν} ∝ L^{α} (α ≃ 1), and the coefficient of proportionality between \\dot{ν} and Lα agrees, within a factor of ˜3, with that proposed by Ghosh and Lamb (1979b, ApJ, 234, 296). In the course of the present study, the orbital elements of several sources were refined.

Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells

PubMed Central

2014-01-01

Background The development of immunotherapy has led to significant progress in the treatment of metastatic cancer, including the development of genetic engineering technologies that redirect lymphocytes to recognize and target a wide variety of tumor antigens. Chimeric antigen receptors (CARs) are hybrid proteins combining antibody recognition domains linked to T cell signaling elements. Clinical trials of CAR-transduced peripheral blood lymphocytes (PBL) have induced remission of both solid organ and hematologic malignancies. Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target antigen that is overexpressed in multiple cancer histologies including melanoma, triple-negative breast cancer, glioblastoma, mesothelioma and sarcoma. Methods CSPG4 expression in cancer cell lines was assayed using flow cytometry (FACS) and reverse-transcription PCR (RT-PCR). Immunohistochemistry was utilized to assay resected melanomas and normal human tissues (n = 30) for CSPG4 expression and a reverse-phase protein array comprising 94 normal tissue samples was also interrogated for CSPG4 expression. CARs were successfully constructed from multiple murine antibodies (225.28S, TP41.2, 149.53) using second generation (CD28.CD3ζ) signaling domains. CAR sequences were cloned into a gamma-retroviral vector with subsequent successful production of retroviral supernatant and PBL transduction. CAR efficacy was assayed by cytokine release and cytolysis following coculture with target cell lines. Additionally, glioblastoma stem cells were generated from resected human tumors, and CSPG4 expression was determined by RT-PCR and FACS. Results Immunohistochemistry demonstrated prominent CSPG4 expression in melanoma tumors, but failed to demonstrate expression in any of the 30 normal human tissues studied. Two of 94 normal tissue protein lysates were positive by protein array. CAR constructs demonstrated cytokine secretion and cytolytic function after co-culture with tumor cell lines from multiple different histologies, including melanoma, breast cancer, mesothelioma, glioblastoma and osteosarcoma. Furthermore, we report for the first time that CSPG4 is expressed on glioblastoma cancer stem cells (GSC) and demonstrate that anti-CSPG4 CAR-transduced T cells recognize and kill these GSC. Conclusions The functionality of multiple different CARs, with the widespread expression of CSPG4 on multiple malignancies, suggests that CSPG4 may be an attractive candidate tumor antigen for CAR-based immunotherapies using appropriate technology to limit possible off-tumor toxicity. PMID:25197555

A Thermal Infrared Imaging Study of Very Low Mass, Wide-separation Brown Dwarf Companions to Upper Scorpius Stars: Constraining Circumstellar Environments

NASA Astrophysics Data System (ADS)

Bailey, Vanessa; Hinz, Philip M.; Currie, Thayne; Su, Kate Y. L.; Esposito, Simone; Hill, John M.; Hoffmann, William F.; Jones, Terry; Kim, Jihun; Leisenring, Jarron; Meyer, Michael; Murray-Clay, Ruth; Nelson, Matthew J.; Pinna, Enrico; Puglisi, Alfio; Rieke, George; Rodigas, Timothy; Skemer, Andrew; Skrutskie, Michael F.; Vaitheeswaran, Vidhya; Wilson, John C.

2013-04-01

We present a 3-5 μm LBT/MMT adaptive optics imaging study of three Upper Scorpius stars with brown dwarf (BD) companions with very low masses/mass ratios (M BD <25 M Jup; M BD/M sstarf ≈ 1%-2%) and wide separations (300-700 AU): GSC 06214, 1RXS 1609, and HIP 78530. We combine these new thermal IR data with existing 1-4 μm and 24 μm photometry to constrain the properties of the BDs and identify evidence for circumprimary/circumsecondary disks in these unusual systems. We confirm that GSC 06214B is surrounded by a disk, further showing that this disk produces a broadband IR excess due to small dust near the dust sublimation radius. An unresolved 24 μm excess in the system may be explained by the contribution from this disk. 1RXS 1609B exhibits no 3-4 μm excess, nor does its primary; however, the system as a whole has a modest 24 μm excess, which may come from warm dust around the primary and/or BD. Neither object in the HIP 78530 system exhibits near- to mid-IR excesses. We additionally find that the 1-4 μm colors of HIP 78530B match a spectral type of M3 ± 2, inconsistent with the M8 spectral type assigned based on its near-IR spectrum, indicating that it may be a low-mass star rather than a BD. We present new upper limits on additional low-mass companions in the system (<5 M Jup beyond 175 AU). Finally, we examine the utility of circumsecondary disks as probes of the formation histories of wide BD companions, finding that the presence of a disk may disfavor BD formation near the primary with subsequent outward scattering. Observations reported here were obtained at the LBT and MMT Observatories. The MMT Observatory is a joint facility of the University of Arizona and the Smithsonian Institution. The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are: The University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University; and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota, and University of Virginia.

Multiband Study of Radio Sources of the Rcr Catalogue with Virtual Observatory Tools

NASA Astrophysics Data System (ADS)

Zhelenkova, O. P.; Soboleva, N. S.; Majorova, E. K.; Temirova, A. V.

We present early results of our multiband study of the RATAN Cold Revised (RCR) catalogue obtained from seven cycles of the ``Cold'' survey carried with the RATAN-600 radio telescope at 7.6 cm in 1980--1999, at the declination of the SS 433 source. We used the 2MASS and LAS UKIDSS infrared surveys, the DSS-II and SDSS DR7 optical surveys, as well as the USNO-B1 and GSC-II catalogues, the VLSS, TXS, NVSS, FIRST and GB6 radio surveys to accumulate information about the sources. For radio sources that have no detectable optical candidate in optical or infrared catalogues, we additionally looked through images in several bands from the SDSS, LAS UKIDSS, DPOSS, 2MASS surveys and also used co-added frames in different bands. We reliably identified 76% of radio sources of the RCR catalogue. We used the ALADIN and SAOImage DS9 scripting capabilities, interoperability services of ALADIN and TOPCAT, and also other Virtual Observatory (VO) tools and resources, such as CASJobs, NED, Vizier, and WSA, for effective data access, visualization and analysis. Without VO tools it would have been problematic to perform our study.

Standardized Sky Partitioning for the Next Generation Astronomy and Space Science Archives

NASA Technical Reports Server (NTRS)

Lal, Nand (Technical Monitor); McLean, Brian

2004-01-01

The Johns Hopkins University and Space Telescope Science Institute are working together on this project to develop a library of standard software for data archives that will benefit the wider astronomical community. The ultimate goal was to develop and distribute a software library aimed at providing a common system for partitioning and indexing the sky in manageable sized regions and provide complex queries on the objects stored in this system. Whilst ongoing maintenance work will continue the primary goal has been completed. Most of the next generation sky surveys in the different wavelengths like 2MASS, GALEX, SDSS, GSC-II, DPOSS and FIRST have agreed on this common set of utilities. In this final report, we summarize work on the work elements assigned to the STScI project team.

Update of the FANTOM web resource: high resolution transcriptome of diverse cell types in mammals

PubMed Central

Lizio, Marina; Harshbarger, Jayson; Abugessaisa, Imad; Noguchi, Shuei; Kondo, Atsushi; Severin, Jessica; Mungall, Chris; Arenillas, David; Mathelier, Anthony; Medvedeva, Yulia A.; Lennartsson, Andreas; Drabløs, Finn; Ramilowski, Jordan A.; Rackham, Owen; Gough, Julian; Andersson, Robin; Sandelin, Albin; Ienasescu, Hans; Ono, Hiromasa; Bono, Hidemasa; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R.R.; Kasukawa, Takeya; Kawaji, Hideya

2017-01-01

Upon the first publication of the fifth iteration of the Functional Annotation of Mammalian Genomes collaborative project, FANTOM5, we gathered a series of primary data and database systems into the FANTOM web resource (http://fantom.gsc.riken.jp) to facilitate researchers to explore transcriptional regulation and cellular states. In the course of the collaboration, primary data and analysis results have been expanded, and functionalities of the database systems enhanced. We believe that our data and web systems are invaluable resources, and we think the scientific community will benefit for this recent update to deepen their understanding of mammalian cellular organization. We introduce the contents of FANTOM5 here, report recent updates in the web resource and provide future perspectives. PMID:27794045

STS 134, 135 and 26S Return Samples: Air Quality aboard Shuttle (STS-134) and International Space Station

NASA Technical Reports Server (NTRS)

James, John T.

2011-01-01

This is a very limited set of samples on which to perform an air quality assessment. However, based on these samples, we have no reason to believe that nominal ISS air is unsafe to breathe. We must continue to be vigilant when dealing with nominal atmospheres in ISS. New, unmanned modules require special attention when the crew first enters. Carbon Monoxide Accumulation aboard ISS: Beginning in late 2008 the nominal concentrations of CO began increasing gradually (Figure 1). The results from samples returned on this flight indicate that the CO concentrations, after dropping in late 2009, have cycled upward and then settled back to concentrations near 2 mg/m3. In any case, these changes are well below the 180-day SMAC for CO, which is17 mg/m3. There is no threat to crew health. Carbon Dioxide: This anthropogenic compound has drawn much attention recently because of the possibility that it could contribute to the effects of intracranial hypertension experienced because of spaceflight-induced fluid shifts. From now on we will maintain a plot (Figure 2) of carbon dioxide concentrations ( SD) by averaging the values found in the 3-5 mini-GSC samples taken each month in diverse locations of the ISS. This will enable us to estimate the average exposure of crewmembers to carbon dioxide during their stay aboard the ISS. In general, concentrations are being maintained below 3.5 mmHg. Figure 1

A New Class of Macrocyclic Chiral Selectors for Stereochemical Analysis

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

NONE

1999-03-11

This report summarizes the work accomplished in the authors laboratories over the previous three years. During the funding period they have had 23 monographs published or in press, 1 book chapter, 1 patent issued and have delivered 28 invited seminars or plenary lectures on DOE sponsored research. This report covers the work that has been published (or accepted). The most notable aspect of this work involves the successful development and understanding of a new class of fused macrocyclic compounds as pseudophases and selectors in high performance separations (including high performance liquid chromatography, HPLC; capillary electrophoresis, CE; and thin layer chromatography,more » TLC). They have considerably extended their chiral biomarker work from amber to crude oil and coal. In the process of doing this we've developed several novel separation approaches. They finished their work on the new GSC-PLOT column which is now being used by researchers world-wide for the analysis of gases, light hydrocarbons and halocarbons. Finally, we completed basic studies on immobilizing a cyclodextrin/oligosiloxane hybrid on the wall of fused silica, as well as a basic study on the separation behavior of buckminster fullerene and higher fullerenes.« less

Isolation and Evaluation of Bacillus Strains for Industrial Production of 2,3-Butanediol.

PubMed

Song, Chan Woo; Rathnasingh, Chelladurai; Park, Jong Myoung; Lee, Julia; Song, Hyohak

2018-03-28

Biologically produced 2,3-butanediol (2,3-BDO) has diverse industrial applications. In this study, schematic isolation and screening procedures were designed to obtain generally regarded as safe (GRAS) and efficient 2,3-BDO producers. Over 4,000 candidate strains were isolated by pretreatment and enrichment, and the isolated Bacillus strains were further screened by morphological, biochemical, and genomic analyses. The screened strains were then used to test the utilization of the most common carbon (glucose, xylose, fructose, sucrose) and nitrogen (yeast extract, corn steep liquor) sources for the economical production of 2,3-BDO. Two-stage fed-batch fermentation was finally carried out to enhance 2,3-BDO production. In consequence, a newly isolated Bacillus licheniformis GSC3102 strain produced 92.0 g/l of total 2,3-BDO with an overall productivity and yield of 1.40 g/l/h and 0.423 g/g glucose, respectively, using a cheap and abundant nitrogen source. These results strongly suggest that B. licheniformis , which is found widely in nature, can be used as a host strain for the industrial fermentative production of 2,3-BDO.

Health assessment for Garden State Cleaners Company, Buena Borough, Atlantic City, New Jersey, Region 2. CERCLIS No. NJD053280160. Final report

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

Not Available

1990-09-28

The Garden State Cleaners Company is a dry cleaning establishment located in Buena Borough, New Jersey. Contaminated wastewater from on-site operations was routinely discharged to on-site soils. Analytical data has described significant soil and ground-water contamination from tetrachloroethylene (PCE) and other volatile organic compounds. Ground-water contamination downgradient (to the south) of the site has required the recommended closing of private wells and the installation of a municipal water supply system. An Administrative Order and Notice of Civil Administrative Penalty Assessment (AO and PSO) were issued to Garden State Cleaners in December 1985, requiring GSC to perform a full RI/FS. Municipalmore » water supplies have been made available to affected residens, but utilization is elective. The site was included on the NPL list in March 1989 and is currently ranked 105 of 108 sites in New Jersey. ATSDR and NJDOH consider the Garden State Cleaners site to be of public health concern. The site is being considered for follow-up health study or evaluation.« less

Seismic- and well-log-inferred gas hydrate accumulations on Richards Island

USGS Publications Warehouse

Collett, T.S.

1999-01-01

The gas hydrate stability zone is areally extensive beneath most of the Mackenzie Delta-Beaufort Sea region, with the base of the gas hydrate stability zone more than 1000 m deep on Richards Island. In this study, gas hydrate has been inferred to occur in nine Richards Island exploratory wells on the basis of well-log responses calibrated to the response of the logs within the cored gas-hydrate-bearing intervals of the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well. The integration of the available well-log data with more than 240 km of industry-acquired reflection seismic data have allowed us to map the occurrence of four significant gas hydrate and associated free-gas accumulations in the Ivik-Mallik-Taglu area on Richards Island. The occurrence of gas hydrate on Richards Island is mostly restricted to the crest of large anticlinal features that cut across the base of the gas hydrate stability zone. Combined seismic and well-log data analysis indicate that the known and inferred gas hydrate accumulations on Richards Island may contain as much as 187 178106 m3 of gas.

Desktop Parallax and Proper Motion: A Laboratory Exercise on Astrometry of Asteroids from Project CLEA

NASA Astrophysics Data System (ADS)

Marschall, L. A.; Snyder, G. A.; Good, R. F.; Hayden, M. B.; Cooper, P. R.

1998-12-01

Students in introductory and advanced astronomy classes can now experience the process of discovering asteroids, can measure proper motions, and can actually see the parallax of real astronomical objects on the screen, using a new set of computer-based exercises from Project CLEA. The heart of the exercise is a sophisticated astrometry program "Astrometry of Asteroids", which is a restricted version of CLEA's research software "Tools for Astrometry" described elsewhere at this meeting. The program, as used in the teaching lab, allows students to read and display digital images, co-align pairs of images using designated reference stars, blink and identify moving objects on the pairs, compare images with charts produced from the HST Guide Star Catalog (GSC), and fit equatorial coordinates to the images using designated reference stars from the GSC. Complete technical manuals for the exercise are provided for the use of the instructor, and a set of digital images, in FITS format, is included for the exercise. A student manual is provided for an exercise in which students go through the step-by-step process of determining the tangential velocity of an asteroid. Students first examine a series of images of a near-earth asteroid taken over several hours, blinking pairs to identify the moving object. They next measure the equatorial coordinates on a half-dozen images, and from this calculate an angular velocity of the object. Finally, using a pair of images of the asteroid taken simultaneously at the National Undergraduate Research Observatory (NURO) and at Colgate University, they measure the parallax of the asteroid, and thus its distance, which enables them to convert the angular velocity into a tangential velocity. An optional set of 10 pairs of images is provided, some of which contain asteroids, so that students can try to "find the asteroid" for themselves. The software is extremely flexible, and though materials are provided for a self-contained exercise, teachers can adapt the material to a wide variety of uses. The software and manuals are currently available on the Web. Project CLEA is supported by grants from Gettysburg College and the National Science Foundation.

The Evolution of Galápagos Volcanoes: An Alternative Perspective

NASA Astrophysics Data System (ADS)

Harpp, Karen S.; Geist, Dennis J.

2018-05-01

The older eastern Galápagos are different in almost every way from the historically active western Galápagos volcanoes. The western Galápagos volcanoes have steep upper slopes and are topped by large calderas, whereas none of the older islands has a caldera, an observation that is supported by recent gravity measurements. Moreover, the eastern islands tend to have been constructed by linear fissure systems and many are cut by faults. Most of the western volcanoes erupt evolved basalts with an exceedingly small range of Mg#, Lan/Smn, and Smn/Ybn. This is attributed to homogenization in a crustal-scale magmatic mush column, which is maintained in a thermochemical steady state, owing to high magma supply directly over the Galápagos mantle plume. The exceptions are volcanoes at the leading edge of the hotspot, which have yet to develop mush columns, and volcanoes that are waning in activity, because they are being carried away from the plume. In contrast, the eastern volcanoes erupt relatively primitive magmas, with a large range in Mg#, Lan/Smn, and Smn/Ybn. This is attributed to isolated, ephemeral magmatic plumbing systems supplied by smaller magmatic fluxes throughout their histories. Consequently, each batch of magma follows an independent course of evolution, owing to the low volume of hypersolidus material beneath these volcanoes. The magmatic flux to Galápagos volcanoes negatively correlates with the distance to the Galápagos Spreading Center (GSC). When the ridge was close to the plume, most of the plume-derived magma was directed to the ridge. Currently, the active volcanoes are much farther from the GSC, thus most of the plume-derived magma erupts on the Nazca Plate and can be focused beneath the large young shields. We define an intermediate sub-province comprising Rabida, Santiago and Pinzon volcanoes, which were most active about 1 Ma. They have all erupted dacites, rhyolites, and trachytes, similar to the dying stage of the western volcanoes, indicating that there was a relatively large volume of mush beneath them. Morphologically, however, they are more like the eastern volcanoes, and have erupted lavas with a large range in composition.

CS-09RTVP-1 PROMOTES THE MESENCHYMAL TRANSFORMATION OF GLIOMA STEM CELLS VIA THE CXCR4 AND IL-6 PATHWAYS

PubMed Central

Giladi, Nis; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Poisson, Laila; Mikkelsen, Tom; Ziv-Av, Amotz; Brodie, Chaya

2014-01-01

Glioblastoma (GBM), the most aggressive primary brain tumors, are categorized into the major subgroups: proneural, neural, classical and mesenchymal, the latter being characterized by increased invasion and poor prognosis. We recently identified RTVP-1 as a glioma-associated protein that regulates glioma cell migration and invasion. Using ChiP analyses, we found that the RTVP-1 promoter binds STAT3 and C/EBPbeta, the two master transcription factors that regulate mesenchymal transformation of GBM. Analysis of TCGA tumor specimens demonstrated that the expression of RTVP-1 was higher in the mesenchymal GBM and was inversely correlated with patient survival. We further found that RTVP-1 was expressed in glioma stem cells (GSCs) but not in human neural stem cells (NSCs). Overexpression of RTVP-1 in NSCs induced their mesenchymal transformation, whereas silencing of RTVP-1 in GSCs decreased their mesenchymal signature, increased their neural phenotypes and inhibited the self renewal and stemness of these cells. Silencing of RTVP-1 also decreased tumor volume of GSC-derived xenografts and increased animal survival. Using gene array analysis of RTVP-1 silenced cells we identified IL-6 and CXCR4 as major mediators of RTVP-1 effects on the mesenchymal transformation and self-renewal of GSCs. Using a pull down assay with His-tagged RTVP-1 and FRET analysis, we identified HSP27, N-WASP and hnRNPK as novel interacting proteins of RTVP-1, that mediate its effects on GSC migration and invadopodia formation. In summary, RTVP-1 expression is regulated by STAT3 and CEBPbeta and is promoting the mesenchymal transformation of GSCs. RTVP-1 induces self-renewal and migration of GSCs by the increased expression of IL-6 and CXCR4 and via its interaction with N-WASP, hnRNPK and HSP27. The upregulation of IL-6 by RTVP-1 acts in a positive feedback loop to further increase RTVP-1 expression by activating the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM.

Low Optical Depth Features in Saturn's Rings: The Occultation of GSC5249-01240 by Saturn and Its Rings

NASA Astrophysics Data System (ADS)

Bosh, A. S.; Olkin, C. B.

1996-06-01

On 21 November 1995, Saturn and its rings occulted the star GSC5249-01240 (Bosh & McDonald 1992, Astron. J. 103, 983). Although the star is relatively faint (V = 11.9), other circumstances conspired to make this an excellent event: (i) the normally-bright rings were dark because the sun was crossing through the ring plane, reducing the amount of ring contribution to the background noise and therefore increasing the observed S/N, (ii) the ring opening angle was small (B ~ 3deg ), enhancing detection of low-optical-depth material, and (iii) the low sky-plane velocity allowed longer integration times without loss of spatial resolution. Thus this occultation was particularly well-suited to produce high S/N detections of low-tau ring material. We observed this atmosphere and ring occultation with the Faint Object Spectrograph (FOS) on the Hubble Space Telescope. Using the FOS in its high-speed mode, we sampled the starlight with the G650L grating, recording the stellar signal as a function of both wavelength and time. For the initial analysis of these data, the spectral information was sacrificed by binning all wavelengths together; this in turn increased the detected S/N. We performed a geometric solution for the event, using the known locations of circular ring features as fiducials (Elliot et al., Astron. J. 106, 2544). The scattered light from Saturn and the rings was modelled and subtracted from the light curves to obtain line-of-sight optical depth as a function of ring-plane radius. With these processed data we have made the first occultation detection of Saturn's innermost and very tenuous D ring. We find a line-of-sight optical depth for the thickest part of this ring of tau_ {obs} ~ 0.02. The location and morphology of this feature will be discussed. Comparison of the observed structure will be made with the previous Voyager imaging detection of this ring (Smith et al. 1981, Science 212, 163; Marley & Porco 1993, Icarus 106, 508).

Tectonic reconstruction and geophysical investigations of IOCG occurrences: Great Bear magmatic zone, NT, Canada

NASA Astrophysics Data System (ADS)

Hayward, N.; Corriveau, L.; Enkin, R. J.; Montreuil, J.

2012-12-01

The Geological Survey of Canada's (GSC) Geomapping for Energy and Minerals (GEM) Program is developing and applying new techniques to iron oxide-copper-gold (IOCG) mineral exploration. The Great Bear magmatic zone (GBmz) is the remnants of a Paleoproterozoic continental magmatic arc (~1.872-1.843 Ga), which hosts IOCG mineralisation, including the Au-Co-Bi-Cu NICO deposit. The arc, which was built upon the Hottah terrane during eastward subduction prior to accretion of the Fort Simpson terrane (Hoffman 1980; Hoffman and Bowring 1984; Hildebrand et al. 1987), is dominated by granodiorites with mafic and volcaniclastic rocks towards the margins. Rapakivi and coarse grained biotite granites (ca. 1.866 - 1.856 Ga, Bowring 1984; Gandhi et al. 2001) mark the final plutonic event (Hildebrand et al. 1987), which was followed by extensive NE-striking brittle conjugate faulting (Tirrul 1984), related to final accretion (Hildebrand at al. 2009; Cook 2011). A tectonic reconstruction of the GBmz, which resets major fault offsets associated with final accretion, is based on the interpretation of a new compilation of high-resolution aeromagnetic data (Hayward and Oneschuk 2011) and geological maps (e.g., Hildebrand 2011; Jackson 2008; Jackson and Ootes 2011). The reconstruction provides a snapshot of the geometry of the GBmz at the time of mineralisation (~1.873 - >1.866 Ga, Davis et al. 2011) and a tectonic model for the late-stage setting and evolution of the arc, important in understanding the context of the mineralisation. The model suggests that the NE-striking faults were preceded by extension, perhaps driven by shifting tectonic motions and slab-rollback (Dewey 1980), and associated with NNE-striking faults. Geophysical models developed for the NICO area, which integrate proprietary high-resolution magnetic and gravity data with GSC physical property data, extracted from 872 samples collected from NICO and other sites across the GBmz, clearly delineate the main ore zone and the majority of the local mineral showings. Applied regionally similar models accurately locate known deposits, including NICO and Sue Diane and prospects such as Terra, Grouard Lake, Cole Lake and Echo Bay, and offer possible targets for future exploration.

The Encyclopedia of Systems Biology and OMICS (first presentation) and The ISA Infrastructure for Multi-omics Data (second presentation) (GSC8 Meeting)

ScienceCinema

Kolker, Eugene; Sansone, Susanna

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Eugene Kolker from Seattle Children's Hospital briefly discusses "The Encyclopedia of Systems Biology and OMICS," followed by Susanna Sansone from the EBI on "The ISA Infrastructure for multi-omics data" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA. on Sept. 11, 2009.

The Genomes and Metagenomes (GEM) Catalogue (first presentation) and The ISA-GCDML Workshop (second presentation) (GSC8 Meeting)

ScienceCinema

Field, Dawn; Sansone, Susanna

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding ''Research Coordination Network'' from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology & Hydrology briefly introduces the GEM Catalogue, followed by Susanna Sansone of the European Bioinformatics Institute who talks about the ISA-GCDML workshop at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Physical properties of sediments from the JAPEX/JNOC/GSC Mallik 2L-38 gas hydrate research well

USGS Publications Warehouse

Winters, W.J.

1999-01-01

A 1150 m deep gas hydrate research well was drilled in the Canadian Arctic in February and March 1998 to investigate the interaction between the presence of gas hydrate and the natural conditions presented by the host sediments. Profiles of the following measured and derived properties are presented from that investigation: water content, sediment wet bulk density, grain size, porosity, gas hydrate quantity, and salinity. These data indicate that the greatest concentration of gas hydrate is located within sand and gravel deposits between 897 m and 922 m. American Society for Testing and Materials 1997: Standard test method for specific gravity of soil solids by gas pycnometer D 5550-94; in American Society for Testing and Materials, Annual Book of ASTM Standards, v. 04.09, Soil and Rock, West Conshohocken, Pennsylvania, p. 380-383.

Update of the FANTOM web resource: high resolution transcriptome of diverse cell types in mammals.

PubMed

Lizio, Marina; Harshbarger, Jayson; Abugessaisa, Imad; Noguchi, Shuei; Kondo, Atsushi; Severin, Jessica; Mungall, Chris; Arenillas, David; Mathelier, Anthony; Medvedeva, Yulia A; Lennartsson, Andreas; Drabløs, Finn; Ramilowski, Jordan A; Rackham, Owen; Gough, Julian; Andersson, Robin; Sandelin, Albin; Ienasescu, Hans; Ono, Hiromasa; Bono, Hidemasa; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Kasukawa, Takeya; Kawaji, Hideya

2017-01-04

Upon the first publication of the fifth iteration of the Functional Annotation of Mammalian Genomes collaborative project, FANTOM5, we gathered a series of primary data and database systems into the FANTOM web resource (http://fantom.gsc.riken.jp) to facilitate researchers to explore transcriptional regulation and cellular states. In the course of the collaboration, primary data and analysis results have been expanded, and functionalities of the database systems enhanced. We believe that our data and web systems are invaluable resources, and we think the scientific community will benefit for this recent update to deepen their understanding of mammalian cellular organization. We introduce the contents of FANTOM5 here, report recent updates in the web resource and provide future perspectives. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Permanent installation of fibre-optic DTS cables in boreholes for temperature monitoring

NASA Astrophysics Data System (ADS)

Henninges, J.; Schrötter, J.; Erbas, K.; Böde, S.; Huenges, E.

2003-04-01

Temperature measurements have become an important tool for the monitoring of dynamic processes in the subsurface both in academia and industry. An innovative experimental design for the monitoring of spatial and temporal variations of temperature along boreholes was developed and successfully applied under extreme arctic conditions during a field experiment, which was carried out within the framework of the Mallik 2002 Production Research Well Program*. Three 40 m spaced, 1200 m deep wells were equipped with permanent fibre-optic sensor cables and the variation of temperature was measured deploying the Distributed Temperature Sensing (DTS) technology. The used DTS system enables the simultaneous online registration of temperature profiles along the three boreholes with a maximum spatial resolution of 0.25 m and a minimum sampling interval of 7 sec. After an individual calibration of the fibre-optic sensor cables a resolution of 0.3 °C of the measured temperature data could be achieved. A special feature of the experiment design is the installation of the sensor cables outside the borehole casing. The fibre-optic cables were attached to the outer side of the casing at every connector within intervals of approx. 12 m with cable clamps. The clamps enable a defined positioning of the cable around the perimeter of the casing and are protecting the cable from mechanical damage during installation. After completion the sensor cables are located in the cement annulus between casing and borehole wall. As an example of the performance of the described temperature logging technology data from the reaming of a 300 m thick cement plug inside the borehole is displayed, offering a unique opportunity to explore thermal processes in the near vicinity of a borehole during drilling. The temperature changes image the progress of the drill bit as well as changes in the mud circulation. Furthermore, local effects can be observed that relate to local thermal properties and technical features of the cable installation. (*) The program participants include 8 partners; The Geological Survey of Canada (GSC), The Japan National Oil Corporation (JNOC), GeoForschungsZentrum Potsdam (GFZ), United States Geological Survey (USGS), United States Department of the Energy (USDOE), India Ministry of Petroleum and Natural Gas (MOPNG)/Gas Authority of India (GAIL) and the Chevron-BP-Burlington joint venture group.

The Geohazard Safety Classification: how resilience could play a role in the geo-hydrological hazards assessment of school buildings.

NASA Astrophysics Data System (ADS)

Pazzi, Veronica; Morelli, Stefano; Casagli, Nicola

2016-04-01

The impacts of adverse events related to geological hazards are unevenly distributed among communities and groups of individuals concentrated in restricted workplaces. Their consequent safety level is the result of differential exposures to these events and of diversified levels of preparation to them. Nowadays, the exposure and coping ability as co-determinants of people's safety are of particular interest for institutions managing the schools systems. According to the disaster risk reduction experts, the geo-hydrological processes can be mitigated with knowledge and planning, physical and environmental protection measures, and response preparedness. UNISDR is promoting a global culture of safety and resilience through the integration of disaster risk reduction in school curricula. The Comprehensive School Safety (CSS) framework is intended to advance the goals of the Worldwide Initiative for Safe Schools and the Global Alliance for Disaster Risk Reduction and Resilience in the Education Sector, and to promote school safety as a priority area of post-2015 frameworks for sustainable development, risk reduction and resilience. In Italy, according the latest ministerial survey (June 2010), there are 41,902 school buildings. Their alarming condition in terms of safety for their daily occupants is reflected by 39 fatalities ascribable to structural failures in the last 21 years. In 95% of these cases victims are a sad tribute due to natural phenomena. A rigorous evaluation of the total risk of a school building, as defined by the well known risk equation (R=HxVxE), would require a complete probability density function describing the exposure to specific types of events of all the pupils and personnel in the school. In addition, the probability that the inhabitants are present in the school during an event should be estimated depending on the time of day, day of week, or month of the year, as well as on local holiday schedules. The inclusion of resilience as a component of risk allows us to refine the risk awareness, focusing attention on the cultural and social meaning of risk as a shared practice among communities that are potentially at risk. This project developed a method for assessing school hazard exposure (landslide, seismic, flood) and structural fragility/safe learning facilities (seismic response, dampness, plan configuration) which is non-invasive, fairly quick and objective. This tool, which is based on the GSC (Geohazard Safety Classification) definition, was tested in central Italy and optimized for a very wide variety of situations, so that it may be exported in schools (or in similar working places) of other geographical areas. The GSC was obtained as the complementary to one of the Index of Geohazard Impact (IGI), calculated modifying the equation of the specific risk, taking into account also the resilience as a damper, amplifier or invariant of the specific risk itself (IGI=max(HixVi)/rho). The variables of this new equation (hazard, vulnerability and resilience) can be quantified on the basis of ancillary data (thematic maps), results of the data processing of field surveys (seismic noise measure according to the H/V technique, thermographic images, GPS surveys) and the answers to an online questionnaire implemented on purpose.

Graph clustering techniques applied to the glycomic response in glioblastoma cells to treatments with STAT3 phosphorylation inhibition and fetal bovine serum

NASA Astrophysics Data System (ADS)

Görke, Robert; Meyer-Bäse, Anke; Plant, Claudia; He, Huan; Emmett, Mark R.; Nilsson, Carol; Colman, Howard; Conrad, Charles A.

2011-06-01

Cancer stem cells (CSC) represent a very small percentage of the total tumor population however they pose a big challenge in treating cancer. Glycans play a key role in cancer therapeutics since overexpression of them depending on the glycan type can lead either to cell death or more invasive metastasis. Two major components, fetal bovine serum (FBS) and STAT3, are known to up- or down-regulate certain glycolipid or phospholipid compositions found in glioblastoma CSCs. The analysis and the understanding of the global interactional behavior of lipidomic networks remains a challenging task and can not be accomplished solely based on intuitive reasoning. The present contribution aims at applying graph clustering networks to analyze the functional aspects of certain activators or inhibitors at the molecular level in glioblastoma stem cells (GSCs). This research enhances our understanding of the differences in phenotype changes and determining the responses of glycans to certain treatments for the aggressive GSCs, and represents together with a quantitative phosphoproteomic study1 the most detailed systems biology study of GSCs differentiation known so far. Thus, these new paradigms are providing unique understanding of the mechanisms involved in GSC maintenance and tumorigenicity and are thus opening a new window to biomedical frontiers.

Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

ScienceCinema

Vaughan, Bob; Kaye, Jon

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Betty Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

The Human Microbiome Project (HMP) and the Data Analysis and Coordination Center (DAAC) Portal to the HMP (GSC8 Meeting)

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

Weinstock, George; Wortman, Jennifer

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. George Weinstock from Washington University School of Medicine talks about the Human Microbiome Project (HMP) followed briefly by Jennifer Wortman from the University ofmore » Maryland School of Medicine on the Data Analysis and Coordination Center (DACC) portal to the HMP at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587.

PubMed

Figueroa, Javier; Phillips, Lynette M; Shahar, Tal; Hossain, Anwar; Gumin, Joy; Kim, Hoon; Bean, Andrew J; Calin, George A; Fueyo, Juan; Walters, Edgar T; Kalluri, Raghu; Verhaak, Roel G; Lang, Frederick F

2017-11-01

Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808-19. ©2017 AACR . ©2017 American Association for Cancer Research.

The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

PubMed

Xie, Yuan; Bergström, Tobias; Jiang, Yiwen; Johansson, Patrik; Marinescu, Voichita Dana; Lindberg, Nanna; Segerman, Anna; Wicher, Grzegorz; Niklasson, Mia; Baskaran, Sathishkumar; Sreedharan, Smitha; Everlien, Isabelle; Kastemar, Marianne; Hermansson, Annika; Elfineh, Lioudmila; Libard, Sylwia; Holland, Eric Charles; Hesselager, Göran; Alafuzoff, Irina; Westermark, Bengt; Nelander, Sven; Forsberg-Nilsson, Karin; Uhrbom, Lene

2015-10-01

Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

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

Vaughan, Bob; Kaye, Jon

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Bettymore » Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

The Human Microbiome Project (HMP) and the Data Analysis and Coordination Center (DAAC) Portal to the HMP (GSC8 Meeting)

ScienceCinema

Weinstock, George; Wortman, Jennifer

2018-01-22

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. George Weinstock from Washington University School of Medicine talks about the Human Microbiome Project (HMP) followed briefly by Jennifer Wortman from the University of Maryland School of Medicine on the Data Analysis and Coordination Center (DACC) portal to the HMP at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

The Encyclopedia of Systems Biology and OMICS (first presentation) and The ISA Infrastructure for Multi-omics Data (second presentation) (GSC8 Meeting)

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

Kolker, Eugene; Sansone, Susanna

2011-09-11

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Eugene Kolker from Seattle Children's Hospital briefly discusses "The Encyclopedia of Systems Biology and OMICS," followed by Susanna Sansone from the EBI on "Themore » ISA Infrastructure for multi-omics data" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA. on Sept. 11, 2009.« less

Design and synthesis of 2-oxindole based multi-targeted inhibitors of PDK1/Akt signaling pathway for the treatment of glioblastoma multiforme.

PubMed

Sestito, Simona; Nesi, Giulia; Daniele, Simona; Martelli, Alma; Digiacomo, Maria; Borghini, Alice; Pietra, Daniele; Calderone, Vincenzo; Lapucci, Annalina; Falasca, Marco; Parrella, Paola; Notarangelo, Angelantonio; Breschi, Maria C; Macchia, Marco; Martini, Claudia; Rapposelli, Simona

2015-11-13

Aggressive behavior and diffuse infiltrative growth are the main features of Glioblastoma multiforme (GBM), together with the high degree of resistance and recurrence. Evidence indicate that GBM-derived stem cells (GSCs), endowed with unlimited proliferative potential, play a critical role in tumor development and maintenance. Among the many signaling pathways involved in maintaining GSC stemness, tumorigenic potential, and anti-apoptotic properties, the PDK1/Akt pathway is a challenging target to develop new potential agents able to affect GBM resistance to chemotherapy. In an effort to find new PDK1/Akt inhibitors, we rationally designed and synthesized a small family of 2-oxindole derivatives. Among them, compound 3 inhibited PDK1 kinase and downstream effectors such as CHK1, GS3Kα and GS3Kβ, which contribute to GCS survival. Compound 3 appeared to be a good tool for studying the role of the PDK1/Akt pathway in GCS self-renewal and tumorigenicity, and might represent the starting point for the development of more potent and focused multi-target therapies for GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Overview of the 2006-2008 JOGMEC/NRCan/Aurora Mallik Gas Hydrate Production Test Program

NASA Astrophysics Data System (ADS)

Yamamoto, K.; Dallimore, S. R.

2008-12-01

During the winters of 2007 and 2008 the Japan Oil, Gas and Metals National Corporation (JOGMEC) and Natural Resources Canada (NRCan), with Aurora Research Institute as the operator, carried out an on-shore gas hydrate production test program at the Mallik site, Mackenzie Delta, Northwest Territories, Canada. The prime objective of the program was to verify the feasibility of depressurization technique by drawing down the formation pressure across a 12m perforated gas hydrate bearing section. This project was the second full scale production test at this site following the 2002 Japex/JNOC/GSC et al Mallik research program in which seven participants organizatinos from five countries undertook a thermal test using hot water circulation Field work in 2007 was devoted to establishing a production test well, installing monitoring devices outside of casing, conducting base line geophysical studies and undertaking a short test to gain practical experience prior to longer term testing planned for 2008 . Hydrate-dissociated gas was produced to surface by depressurization achieved by lowering the fluid level with a dowhole pump. However, the operation was terminated 60 hours after the start of the pumping mainly due to sand production problems. In spite of the short period (12.5 hours of ellapsed pumping time), at least 830m3 of the gas was produced and accumulated in the borehole. Sand screens were installed across the perforated interval at the bottom hole for the 2008 program to overcome operational problems encountered in 2007 and achieve sustainable gas production. Stable bottom hole flowing pressures were successfully achieved during a 6 day test with continuous pump operation. Sustained gas production was achieved with rates between 2000- 4000m3/day and cummulative gas volume in the surface of approximately 13,000m3. Temperature and pressure data measured at the bottom hole and gas and water production rates gave positive evidence for the high efficiency of gas production through depressurization method. Pre and post produciton testing geophysical logging program, geochemical analyses and monitoring tools outside of the casing also derived the supporting data for the formation responses to the depressurization. Acknowledgements: METI, MH21, JOGMEC and NRCan, Government of NWT, 2002 partners, IPM, R&D team members.

HAT-P-18b AND HAT-P-19b: TWO LOW-DENSITY SATURN-MASS PLANETS TRANSITING METAL-RICH K STARS

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

Hartman, J. D.; Bakos, G. A.; Torres, G.

2011-01-01

We report the discovery of two new transiting extrasolar planets. HAT-P-18b orbits the V = 12.759 K2 dwarf star GSC 2594-00646, with a period P = 5.508023 {+-} 0.000006 days, transit epoch T{sub c} = 2454715.02174 {+-} 0.00020 (BJD), and transit duration 0.1131 {+-} 0.0009 days. The host star has a mass of 0.77 {+-} 0.03 M{sub sun}, radius of 0.75 {+-} 0.04 R{sub sun}, effective temperature 4803 {+-} 80 K, and metallicity [Fe/H] = +0.10 {+-} 0.08. The planetary companion has a mass of 0.197 {+-} 0.013 M{sub J} and radius of 0.995 {+-} 0.052 R{sub J}, yielding amore » mean density of 0.25 {+-} 0.04 g cm{sup -3}. HAT-P-19b orbits the V = 12.901 K1 dwarf star GSC 2283-00589, with a period P = 4.008778 {+-} 0.000006 days, transit epoch T{sub c} = 2455091.53417 {+-} 0.00034 (BJD), and transit duration 0.1182 {+-} 0.0014 days. The host star has a mass of 0.84 {+-} 0.04 M{sub sun}, radius of 0.82 {+-} 0.05 R{sub sun}, effective temperature 4990 {+-} 130 K, and metallicity [Fe/H] = +0.23 {+-} 0.08. The planetary companion has a mass of 0.292 {+-} 0.018 M{sub J} and radius of 1.132 {+-} 0.072 R{sub J}, yielding a mean density of 0.25 {+-} 0.04 g cm{sup -3}. The radial velocity residuals for HAT-P-19 exhibit a linear trend in time, which indicates the presence of a third body in the system. Comparing these observations with theoretical models, we find that HAT-P-18b and HAT-P-19b are each consistent with a hydrogen-helium-dominated gas giant planet with negligible core mass. HAT-P-18b and HAT-P-19b join HAT-P-12b and WASP-21b in an emerging group of low-density Saturn-mass planets, with negligible inferred core masses. However, unlike HAT-P-12b and WASP-21b, both HAT-P-18b and HAT-P-19b orbit stars with super-solar metallicity. This calls into question the heretofore suggestive correlation between the inferred core mass and host star metallicity for Saturn-mass planets.« less

HAT-P-20b-HAT-P-23b: FOUR MASSIVE TRANSITING EXTRASOLAR PLANETS

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

Bakos, G. A.; Hartman, J.; Torres, G.

We report the discovery of four relatively massive (2-7 M{sub J}) transiting extrasolar planets. HAT-P-20b orbits the moderately bright V = 11.339 K3 dwarf star GSC 1910-00239 on a circular orbit, with a period P = 2.875317 {+-} 0.000004 days, transit epoch T{sub c} = 2455080.92661 {+-} 0.00021 (BJD{sub UTC}), and transit duration 0.0770 {+-} 0.0008 days. The host star has a mass of 0.76 {+-} 0.03 M{sub Sun }, radius of 0.69 {+-} 0.02 R{sub Sun }, effective temperature 4595 {+-} 80 K, and metallicity [Fe/H] = +0.35 {+-} 0.08. The planetary companion has a mass of 7.246 {+-}more » 0.187 M{sub J} and a radius of 0.867 {+-} 0.033 R{sub J} yielding a mean density of 13.78 {+-} 1.50 g cm{sup -3}. HAT-P-21b orbits the V = 11.685 G3 dwarf star GSC 3013-01229 on an eccentric (e = 0.228 {+-} 0.016) orbit, with a period P = 4.124481 {+-} 0.000007 days, transit epoch T{sub c} = 2454996.41312 {+-} 0.00069, and transit duration 0.1530 {+-} 0.0027 days. The host star has a mass of 0.95 {+-} 0.04 M{sub Sun }, radius of 1.10 {+-} 0.08 R{sub Sun }, effective temperature 5588 {+-} 80 K, and metallicity [Fe/H] = +0.01 {+-} 0.08. The planetary companion has a mass of 4.063 {+-} 0.161 M{sub J} and a radius of 1.024 {+-} 0.092 R{sub J} yielding a mean density of 4.68{sup +1.59}{sub -0.99} g cm{sup -3}. HAT-P-21b is a borderline object between the pM and pL class planets, and the transits occur near apastron. HAT-P-22b orbits the bright V = 9.732 G5 dwarf star HD 233731 on a circular orbit, with a period P = 3.212220 {+-} 0.000009 days, transit epoch T{sub c} = 2454930.22001 {+-} 0.00025, and transit duration 0.1196 {+-} 0.0014 days. The host star has a mass of 0.92 {+-} 0.03 M{sub Sun }, radius of 1.04 {+-} 0.04 R{sub Sun }, effective temperature 5302 {+-} 80 K, and metallicity [Fe/H] = +0.24 {+-} 0.08. The planet has a mass of 2.147 {+-} 0.061 M{sub J} and a compact radius of 1.080 {+-} 0.058 R{sub J} yielding a mean density of 2.11{sup +0.40}{sub -0.29} g cm{sup -3}. The host star also harbors an M-dwarf companion at a wide separation. Finally, HAT-P-23b orbits the V = 12.432 G0 dwarf star GSC 1632-01396 on a close to circular orbit, with a period P = 1.212884 {+-} 0.000002 days, transit epoch T{sub c} = 2454852.26464 {+-} 0.00018, and transit duration 0.0908 {+-} 0.0007 days. The host star has a mass of 1.13 {+-} 0.04 M{sub Sun }, radius of 1.20 {+-} 0.07 R{sub Sun }, effective temperature 5905 {+-} 80 K, and metallicity [Fe/H] = +0.15 {+-} 0.04. The planetary companion has a mass of 2.090 {+-} 0.111 M{sub J} and a radius of 1.368 {+-} 0.090 R{sub J} yielding a mean density of 1.01 {+-} 0.18 g cm{sup -3}. HAT-P-23b is an inflated and massive hot Jupiter on a very short period orbit, and has one of the shortest characteristic infall times (7.5{sup +2.9}{sub -1.8} Myr) before it gets engulfed by the star.« less

Tsunami hazard, vulnerability and impact assessment of the coastal area of Rabat, Morocco

NASA Astrophysics Data System (ADS)

Lesne, Olivia; Mangin, Antoine; Renou, Camille; Rouffi, Frédéric; Atillah, Abderrahman; Moudni, Hicham

2010-05-01

Among African countries, Morocco is probably one of the most exposed to tsunami hazard. Indeed, Morocco is integrated in the particular geodynamic context of the northern African margin characterized by the existence of the Azores-Gibraltar fault separating two active tectonic plates: the African and the Eurasian plates. This area generated and still generates many large earthquakes exceeding a magnitude of 6. The Moroccan Atlantic coasts are thus exposed to tsunamigenic earthquakes occurring offshore. Tsunamis generated in this area are not frequent but can be really disastrous and could have a huge impact. In the framework of the SCHEMA project, a 3 year European project, we studied the consequences on the Moroccan coastal area of two potential tsunami scenarios, applying the generic methodology developed during the project for building tsunami vulnerability and impact maps. The study focuses on the "Rabat Zaïr" region. Centred on the Bouregreg Valley, this study area encompasses three main coastal and densely populated towns of Morocco: Rabat (capital), Salé and Temara. Using a combination of numerical modelling, field surveys, earth observation and GIS data, the risk has been evaluated for this highly vulnerable area (flat topography, small beaches with many tourists in summer, presence of several bridges on the Bouregreg river separating Rabat and Salé, presence of a dam upstream the 2 cities, and development of a new residential and touristic complex on the coastline and in the vicinity of the estuary). Two scenarios of tsunami have been studied to estimate the hazard on the coastal zone of Rabat: a worst case scenario based on the historical Lisbon earthquake of 1755 as well as a moderate scenario based on the historical Portugal earthquake of 1969. For each scenario, numerical models allowed to produce inundation maps consisting of inundation limits as well as maximum water heights. Land use data together with earth observation data interpretation allowed then to generate a building classification. Finally potential damages are derived using damage functions developed during the project by Geosciences Consultants (GSC), by crossing information from hazard maps (maximum water elevations) with building vulnerability maps. The damage maps will then serve as a base for elaborating evacuation plans with appropriate rescue and relief processes useful for decision makers, local authorities and investors.

Evaluation of seismic design spectrum based on UHS implementing fourth-generation seismic hazard maps of Canada

NASA Astrophysics Data System (ADS)

Ahmed, Ali; Hasan, Rafiq; Pekau, Oscar A.

2016-12-01

Two recent developments have come into the forefront with reference to updating the seismic design provisions for codes: (1) publication of new seismic hazard maps for Canada by the Geological Survey of Canada, and (2) emergence of the concept of new spectral format outdating the conventional standardized spectral format. The fourth -generation seismic hazard maps are based on enriched seismic data, enhanced knowledge of regional seismicity and improved seismic hazard modeling techniques. Therefore, the new maps are more accurate and need to incorporate into the Canadian Highway Bridge Design Code (CHBDC) for its next edition similar to its building counterpart National Building Code of Canada (NBCC). In fact, the code writers expressed similar intentions with comments in the commentary of CHBCD 2006. During the process of updating codes, NBCC, and AASHTO Guide Specifications for LRFD Seismic Bridge Design, American Association of State Highway and Transportation Officials, Washington (2009) lowered the probability level from 10 to 2% and 10 to 5%, respectively. This study has brought five sets of hazard maps corresponding to 2%, 5% and 10% probability of exceedance in 50 years developed by the GSC under investigation. To have a sound statistical inference, 389 Canadian cities are selected. This study shows the implications of the changes of new hazard maps on the design process (i.e., extent of magnification or reduction of the design forces).

Modulation of WNT signaling activity is key to the formation of the embryonic head.

PubMed

Fossat, Nicolas; Jones, Vanessa; Garcia-Garcia, Maria J; Tam, Patrick P L

2012-01-01

The formation of the embryonic head begins with the assembly of the progenitor tissues of the brain, the head and face primordia and the foregut that are derived from the primary germ layers during gastrulation. Specification of the anterior-posterior polarity of major body parts and the morphogenesis of the head and brain specifically is driven by inductive signals including those mediated by BMP, Nodal, FGF and WNT. A critical role of β-catenin dependent WNT signalling activity for head morphogenesis has been revealed through the analysis of the phenotypic impact of loss of function mutation of an antagonist: DKK1, a transcriptional repressor: GSC; and the outcome of interaction of Dkk1 with genes coding three components of the canonical signalling pathway: the ligand WNT3, the co-receptor LRP6 and the transcriptional co-factor, β-catenin. The findings highlight the requirement of a stringent control of the timing, domain and level of canonical WNT signalling activity for the formation of the embryonic head.

Characterizing Giant Exoplanets through Multiwavelength Transit Observations: XO-1 b

NASA Astrophysics Data System (ADS)

Cole, Jackson Lane; Gardner, Cristilyn N.; Garver, Bethany R.; Jarka, Kyla L.; Kar, Aman; McGough, Aylin M.; PeQueen, David J.; Rivera, Daniel Ivan; Kasper, David; Jang-Condell, Hannah; Kobulnicky, Henry; Dale, Daniel

2018-01-01

Multiwavelength observations of transiting exoplanets can reveal wavelength dependence of the observed transit depth (or a lack thereof), thereby allowing for thorough characterization of their atmospheres. In support of a larger project performing these characterizations of 12 transiting giant exoplanets through 66 nights of continuous observation at the 2.3 m Wyoming Infrared Observatory (WIRO), we report an updated ephemeris for transiting exoplanet XO- 1 b. We carried out an MCMC analysis on photometric data obtained using the standard broad bandpass Sloan filter system. Our data set for XO-1 b is the most limited of those contributing to the larger project, the target having only been successfully observed from the transit midpoint to the egress on one night with limited out-of-transit data available. Exoplanet XO-1 b is a planet transiting star XO-1 (GSC 02041-01657) of type G1 V with V = 11.19 McCullough et al. (2006). This work is supported by the National Science Foundation under REU grant AST 1560461.

The novel tumour suppressor Madm regulates stem cell competition in the Drosophila testis

PubMed Central

Singh, Shree Ram; Liu, Ying; Zhao, Jiangsha; Zeng, Xiankun; Hou, Steven X.

2016-01-01

Stem cell competition has emerged as a mechanism for selecting fit stem cells/progenitors and controlling tumourigenesis. However, little is known about the underlying molecular mechanism. Here we identify Mlf1-adaptor molecule (Madm), a novel tumour suppressor that regulates the competition between germline stem cells (GSCs) and somatic cyst stem cells (CySCs) for niche occupancy. Madm knockdown results in overexpression of the EGF receptor ligand vein (vn), which further activates EGF receptor signalling and integrin expression non-cell autonomously in CySCs to promote their overproliferation and ability to outcompete GSCs for niche occupancy. Conversely, expressing a constitutively activated form of the Drosophila JAK kinase (hopTum−l) promotes Madm nuclear translocation, and suppresses vn and integrin expression in CySCs that allows GSCs to outcompete CySCs for niche occupancy and promotes GSC tumour formation. Tumour suppressor-mediated stem cell competition presented here could be a mechanism of tumour initiation in mammals. PMID:26792023

The novel tumour suppressor Madm regulates stem cell competition in the Drosophila testis.

PubMed

Singh, Shree Ram; Liu, Ying; Zhao, Jiangsha; Zeng, Xiankun; Hou, Steven X

2016-01-21

Stem cell competition has emerged as a mechanism for selecting fit stem cells/progenitors and controlling tumourigenesis. However, little is known about the underlying molecular mechanism. Here we identify Mlf1-adaptor molecule (Madm), a novel tumour suppressor that regulates the competition between germline stem cells (GSCs) and somatic cyst stem cells (CySCs) for niche occupancy. Madm knockdown results in overexpression of the EGF receptor ligand vein (vn), which further activates EGF receptor signalling and integrin expression non-cell autonomously in CySCs to promote their overproliferation and ability to outcompete GSCs for niche occupancy. Conversely, expressing a constitutively activated form of the Drosophila JAK kinase (hop(Tum-l)) promotes Madm nuclear translocation, and suppresses vn and integrin expression in CySCs that allows GSCs to outcompete CySCs for niche occupancy and promotes GSC tumour formation. Tumour suppressor-mediated stem cell competition presented here could be a mechanism of tumour initiation in mammals.

16 KB/S Modem (AN/GSC-38) CONUS Test

DTIC Science & Technology

1980-08-01

1.4E-3 1500 MOS 2.5-4 1400 6 LEE 4.3E-3 1640 B MEM 0 1440 POl 2.5E-3 1860 ARL 5.0-5 1580 TOL I.1E-3 1900 DRA 2.0-5 150 NET 3.5E-3 2000 SEG 1.1-4 19yno C...LAM-POL 1.6-3 0.60 0.40 F’I,-LAM 1.2-4 0.63 0.37 LAM- MEM 4.8-3 0.53 0.47 SOC-POL j.,1-4 0.50 0.50 LAM-ORE 7.8-3 O.G2 0.38 SOC-YAK 1.4-3 0.65 0.35 MOU...0.61 0.39 NBD-HEL 4.5-4 0.84 0.16 NBD-CMC 3.2 4 1.0 0 NBD-LAM 7.8-3 0.25 0.75 NBD--MOU 2.7-3 0.48 0.52 NBD- MEM 5.6-3 0.14 0.86 NBD-JAS 5.3-3 0.69

XEphem: Interactive Astronomical Ephemeris

NASA Astrophysics Data System (ADS)

Downey, Elwood Charles

2011-12-01

XEphem is a scientific-grade interactive astronomical ephemeris package for UNIX-like systems. Written in C, X11 and Motif, it is easily ported to systems. Among other things, XEphem: computes heliocentric, geocentric and topocentric information for all objects; has built-in support for all planets; the moons of Mars, Jupiter, Saturn, Uranus and Earth; central meridian longitude of Mars and Jupiter; Saturn's rings; and Jupiter's Great Red Spot; allows user-defined objects including stars, deepsky objects, asteroids, comets and Earth satellites; provides special efficient handling of large catalogs including Tycho, Hipparcos, GSC; displays data in configurable tabular formats in conjunction with several interactive graphical views; displays a night-at-a-glance 24 hour graphic showing when any selected objects are up; displays 3-D stereo Solar System views that are particularly well suited for visualizing comet trajectories; quickly finds all close pairs of objects in the sky; and sorts and prints all catalogs with very flexible criteria for creating custom observing lists. Its capabilities are listed more fully in the user manual introduction.

IGFBP2 promotes glioma tumor stem cell expansion and survival

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

Hsieh, David, E-mail: dhs.zfs@gmail.com; Hsieh, Antony; Stea, Baldassarre

2010-06-25

IGFBP2 is overexpressed in the most common brain tumor, glioblastoma (GBM), and its expression is inversely correlated to GBM patient survival. Previous reports have demonstrated a role for IGFBP2 in glioma cell invasion and astrocytoma development. However, the function of IGFBP2 in the restricted, self-renewing, and tumorigenic GBM cell population comprised of tumor-initiating stem cells has yet to be determined. Herein we demonstrate that IGFBP2 is overexpressed within the stem cell compartment of GBMs and is integral for the clonal expansion and proliferative properties of glioma stem cells (GSCs). In addition, IGFBP2 inhibition reduced Akt-dependent GSC genotoxic and drug resistance.more » These results suggest that IGFBP2 is a selective malignant factor that may contribute significantly to GBM pathogenesis by enriching for GSCs and mediating their survival. Given the current dearth of selective molecular targets against GSCs, we anticipate our results to be of high therapeutic relevance in combating the rapid and lethal course of GBM.« less

New Herbig-Haro objects in the L1617 and L1646 dark clouds

NASA Astrophysics Data System (ADS)

Wang, H.; Stecklum, B.; Henning, Th.

2005-07-01

Optical imaging towards L1617 and L1646 revealed three new Herbig-Haro (HH) objects, HH 182, 439, and 866. Spectroscopic observations of HH 182 A and 439 A confirmed their HH object nature. Molecular hydrogen v = 1-0 S(1) narrow band imaging revealed three H2 emission features in the HH 182 region which coincide with the optical emission. Based on the position angles of the different parts of the HH 111 flow and that of HH 182, HH 182 may be the outermost southeastern part of the giant HH 111 flow. One deeply embedded star is revealed in our near-infrared imaging of the HH 439 region. HH 439 A and the associated bow shock are probably driven by the newly detected embedded star. HH 439 B-D are probably driven by the Herbig AeBe star candidate GSC 04794-00827 (IRAS 06045-0554). The embedded source IRAS 06046-0603 is identified to be the exciting source of HH 866.

Assessment of Air Quality in the Shuttle and International Space Station (ISS) Based on Samples Returned by STS-102 at the Conclusion of 5A.1

NASA Technical Reports Server (NTRS)

James, John T.

2001-01-01

The toxicological assessment of air samples returned at the end of the STS-102 (5A.1) flight to the ISS is reported. ISS air samples were taken in late February 2001 from the Service Module, FGB, and U.S. Laboratory using grab sample canisters (GSCs) and/or formaldehyde badges . A "first-entry" sample of the multipurpose logistics module (MPLM) atmosphere was taken with a GSC, and preflight and end-of-mission samples were obtained from Discovery using GSCs. Analytical methods have not changed from earlier reports, and all quality control measures were met for the data presented herein. The two general criteria used to assess air quality are the total-non-methane-volatile organic hydrocarbons (NMVOCs) and the total T-value (minus the CO2 contribution). Control of atmospheric alcohols is important to the water recovery system engineers, hence total alcohols were also assessed in each sample. Formaldehyde is quantified separately.

A Spanish validation of the Coma Recovery Scale-Revised (CRS-R).

PubMed

Tamashiro, Mercedes; Rivas, Maria Elisa; Ron, Melania; Salierno, Fernando; Dalera, Marisol; Olmos, Lisandro

2014-01-01

Analysis of inter-rater reliability and concurrent validity. To determine measurement properties of a Spanish version of The Coma Recovery Scale-Revised (CRS-R). A sample of 35 in-patients with severe acquired brain injury. To test concurrent validity of the translated scale, the Glasgow Coma Scale (GSC) and Disability Rating Scale (DRS) were also administered. Two experts in the field were recruited to assess inter-rater agreement. Inter-rater reliability was good for total CRS-R scores (Cronbach α = 0.973, p = 0.001). Sub-scale analysis showed moderate-to-high inter-rater agreement. Total CRS-R scores correlated significantly (p < 0.05) with total GCS (r = 0.74) and DRS (r = 0.54) scores, indicating acceptable concurrent validity. The Spanish version of CRS-R can be administered reliably by trained and experienced examiners. CRS-R appears capable of differentiating patients in Emergence from Minimally Conscious State (EMCS) or in Minimally Conscious State (MCS) from those in a Vegetative State (VS).

A young solar twin in the Rosette cluster NGC 2244 line of sight

NASA Astrophysics Data System (ADS)

Huber, Jeremy M.; Kielkopf, John F.; Mengel, Matthew; Carter, Bradley D.; Ferland, Gary J.; Clark, Frank O.

2018-05-01

Based on prior precision photometry and cluster age analysis, the bright star GSC 00154-01819 is a possible young pre-main sequence member of the Rosette cluster, NGC 2244. As part of a comprehensive study of the large-scale structure of the Rosette and its excitation by the cluster stars, we noted this star as a potential backlight for a probe of the interstellar medium and extinction along the sight line towards a distinctive nebular feature projected on to the cluster centre. New high-resolution spectra of the star were taken with the University College London Echelle Spectrograph of the AAT. They reveal that rather than being a reddened spectral type B or A star within the Mon OB2 association, it is a nearby, largely unreddened, solar twin of spectral type G2V less than 180 Myr old. It is about 219 pc from the Sun with a barycentric radial velocity of +14.35 ± 1.99 km s-1. The spectrum of the Rosette behind it and along this line of sight shows a barycentric radial velocity of +26.0 ± 2.4 km s-1 in H α, and a full width at half-maximum velocity dispersion of 61.94 ± 1.38 km s-1.

The effect of silver nanoparticles on zebrafish embryonic development and toxicology.

PubMed

Xia, Guangqing; Liu, Tiantian; Wang, Zhenwei; Hou, Yi; Dong, Lihong; Zhu, Junyi; Qi, Jie

2016-06-01

The unique physical and chemical characteristics of nanomaterials, such as the effects of their small size, surface effects, very high rates of reaction, and quantum tunnel effect, have aroused great interest among scholars. However, improper usage has led to an increasing number of nanomaterials entering the environment through various channels, greatly threatening the security of the ecological environment and human health. The urgent need for a scientific assessment of their biosafety can enable nanomaterials to truly benefit humanity. However, the current research in this field is extremely limited with regard to safety standards and waste disposal. In this study, we used silver nanoparticles (nano-Ag) and zebrafish embryos as experimental subjects, and we have reported the deleterious effect on zebrafish embryos treated with different concentrations of nano-Ag, with respect to morphological features (mortality, deformity rate, and heartbeat) and the analysis of expression of relevant genes (sox17, gsc, ntl, otx2); we found a dose-dependent increase in mortality and hatching delay. The results of in situ hybridization indicated that nano-Ag causes a dose-dependent toxicity in embryonic development, and would affect their development and lead to deformity, delayed development, and even death. The safety limit for the concentration of nano-Ag was found to be less than 5 mg/L.

X-ray selected stars in HRC and BHRC catalogues

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.; Paronyan, G. M.

2014-12-01

A joint HRC/BHRC Catalogue has been created based on merging of Hamburg ROSAT Catalogue (HRC) and Byurakan Hamburg ROSAT Catalogue (BHRC). Both have been made by optical identifications of X-ray sources based on low-dispersion spectra of the Hamburg Quasar Survey (HQS) using ROSAT Catalogues. As a result, the largest sample of 8132 (5341+2791) optically identified X-ray sources was created having count rate (CR) of photons ≤ 0.04 ct/s in the area with galactic latitudes |b|≤ 20° and declinations d≤ 0°.There are 4253 AGN, 492 galaxies, 1800 stars and 1587 unknown objects in the sample. All stars have been found in GSC 2.3.2, as well as most of them are in GALEX, USNO-B1.0, 2MASS and WISE catalogues. In addition, 1429 are in SDSS DR9 and 204 have SDSS spectra. For these stars we have carried out spectral classification and along with the bright stars, many new cataclysmic variables (CV), white dwarfs (WD) and late-type stars (K-M and C) have been revealed. For all stars, statistical studies of their multiwavelength properties have been made. An attempt to find a connection between the radiation fluxes in different bands for different types of sources, and identify their characteristics was made as well.

Repurposing phenformin for the targeting of glioma stem cells and the treatment of glioblastoma

PubMed Central

Jiang, Wei; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Brodie, Ziv; Mikkelsen, Tom; Poisson, Laila; Shackelford, David B.; Brodie, Chaya

2016-01-01

Glioblastoma (GBM) is the most aggressive primary brain tumor with poor prognosis. Here, we studied the effects of phenformin, a mitochondrial complex I inhibitor and more potent chemical analog of the diabetes drug metformin on the inhibition of cell growth and induction of apoptosis of glioma stem cells (GSCs) using both in vitro and in vivo models. Phenformin inhibited the self-renewal of GSCs, decreased the expression of stemness and mesenchymal markers and increased the expression of miR-124, 137 and let-7. Silencing of let-7 abrogated phenformin effects on the self-renewal of GSCs via a pathway associated with inhibition of H19 and HMGA2 expression. Moreover, we demonstrate that phenformin inhibited tumor growth and prolonged the overall survival of mice orthotopically transplanted with GSCs. Combined treatments of phenformin and temozolomide exerted an increased antitumor effect on GSCs in vitro and in vivo. In addition, dichloroacetate, an inhibitor of the glycolysis enzyme pyruvate dehydrogenase kinase, that decreases lactic acidosis induced by biguanides, enhanced phenformin effects on the induction of cell death in GSCs and prolonged the survival of xenograft-bearing mice. Our results demonstrate for the first time that phenformin targets GSCs and can be efficiently combined with current therapies for GBM treatment and GSC eradication. PMID:27486821

Repurposing phenformin for the targeting of glioma stem cells and the treatment of glioblastoma.

PubMed

Jiang, Wei; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Brodie, Ziv; Mikkelsen, Tom; Poisson, Laila; Shackelford, David B; Brodie, Chaya

2016-08-30

Glioblastoma (GBM) is the most aggressive primary brain tumor with poor prognosis. Here, we studied the effects of phenformin, a mitochondrial complex I inhibitor and more potent chemical analog of the diabetes drug metformin on the inhibition of cell growth and induction of apoptosis of glioma stem cells (GSCs) using both in vitro and in vivo models. Phenformin inhibited the self-renewal of GSCs, decreased the expression of stemness and mesenchymal markers and increased the expression of miR-124, 137 and let-7. Silencing of let-7 abrogated phenformin effects on the self-renewal of GSCs via a pathway associated with inhibition of H19 and HMGA2 expression. Moreover, we demonstrate that phenformin inhibited tumor growth and prolonged the overall survival of mice orthotopically transplanted with GSCs. Combined treatments of phenformin and temozolomide exerted an increased antitumor effect on GSCs in vitro and in vivo. In addition, dichloroacetate, an inhibitor of the glycolysis enzyme pyruvate dehydrogenase kinase, that decreases lactic acidosis induced by biguanides, enhanced phenformin effects on the induction of cell death in GSCs and prolonged the survival of xenograft-bearing mice. Our results demonstrate for the first time that phenformin targets GSCs and can be efficiently combined with current therapies for GBM treatment and GSC eradication.

The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts.

PubMed

Adhikari, Bandita; Li, Jie; Brandel, Michael G; Futalan, Diahnn; Akers, Johnny; Deming, Timothy; Chen, Clark C; Carter, Bob S

2017-11-01

The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves. Here, we tested the effect of amphiphilic diblock copolypeptide hydrogels (DCHs) of 180-poly-lysine and 20-poly-leucine (K 180 L 20 ) on TMZ using Glioblastoma models. In both the in vitro model, which involved treatment of a human glioblastoma GSC line suspended as neurospheres, and in vivo using an orthotopic glioma xenograft mouse model, we found that K 180 L 20 could safely enhance the efficacy of TMZ. This technique may offer the opportunity to 'coat' the inner lining of the cavity following glioma resection with a slow-release TMZ and potentially decrease recurrence. Future studies in larger animals are needed to delineate this effect. Copyright © 2017. Published by Elsevier Ltd.

Geochemical and Depth Variations at the Galápagos 93.25˚W Propagating Rift

NASA Astrophysics Data System (ADS)

Rotella, M.; Sinton, J.; Mahoney, J.; Chazey, W.

2006-12-01

The 93.25°W propagating rift on the Galápagos Spreading Center (GSC) differs markedly from the better-known propagator at 95.5°W in having the morphology of a classic overlapping spreading center (~24 km of overlap and 7.5 km of offset). It has a higher propagation rate (70 vs 48 mm/yr) [Wilson & Hey, JGR v. 100, 1995] and is breaking through younger crust (260 vs 910 ka); overall magma supply is ~20% greater, as the area is closer to the Galápagos hotspot. The overlapping limbs lack pronounced bathymetric lows, instead they are up to 150 m shallower than the surrounding axial ridges away from the offset. Lavas are T-MORB; failing rift lavas show a slight increase in Mg within the overlap zone but propagating rift lavas lack the strong fractionation anomaly that characterizes the propagating limb at 95.5°W and many other propagating rifts. New major and trace element data on 28 samples from 24 dredge stations along a 175 km section of the GSC spanning the 93.25°W offset indicate significant, systematic variations in mantle sources and melting processes on each limb of the system. Fractionation-corrected ratios of highly to moderately incompatible elements (e.g. La/Yb, Sm/Yb, Zr/Y) show constant values along the propagating rift east of 93.2°W, but within the overlap zone these ratios increase sharply up to a factor of 1.5, then gradually decline to the west. In contrast, the failing rift shows constant to moderately increasing ratios as the overlap zone is approached from the west, with lower overall ratios within the zone. These variations could be interpreted to reflect a counter-intuitive relationship of gradually increasing extent of partial melting with progressive failure of the dying rift, consistent with the striking shoaling of the failing limb, or melting of incompatible-element depleted mantle. Variations along the eastern, propagating rift suggest either a sharp decrease in extent of melting or tapping of a more incompatible-element-enriched mantle source within the overlap zone. Limited Nd-Pb-Sr isotopic data suggest source variations are required in addition to variations in extent of melting. Thus, in contrast to other well-documented propagators where geochemical variations are dominated by magma chamber effects, variations around the 93.25°W system appear to be dominated by melting and source.

Overview of the science activities for the 2002 Mallik gas hydrate production research well program, Mackenzie Delta, N.W.T., Canada

NASA Astrophysics Data System (ADS)

Dallimore, S. R.; Collett, T. S.; Uchida, T.; Weber, M.

2003-04-01

With the completion of scientific studies undertaken as part of the 1998 Mallik 2L-38 gas hydrate research well, an international research site was established for the study of Arctic natural gas hydrates in the Mackenzie Delta of northwestern Canada. Quantitative well log analysis and core studies reveal multiple gas hydrate layers from 890 m to 1106 m depth, exceeding 110 m in total thickness. High gas hydrate saturation values, which in some cases exceed 80% of the pore volume, establish the Mallik gas hydrate field as one of the most concentrated gas hydrate reservoirs in the world. Beginning in December 2001 and continuing to the middle of March 2002, two 1188 m deep science observation wells were drilled and instrumented and a 1166 m deep production research well program was carried out. The program participants include 8 partners; The Geological Survey of Canada (GSC), The Japan National Oil Corporation (JNOC), GeoForschungsZentrum Potsdam (GFZ), United States Geological Survey (USGS), United States Department of the Energy (USDOE), India Ministry of Petroleum and Natural Gas (MOPNG)/Gas Authority of India (GAIL) and the Chevron-BP-Burlington joint venture group. In addition the project has been accepted as part of the International Scientific Continental Drilling Program. The Geological Survey of Canada is coordinating the science program for the project and JAPEX Canada Ltd. acted as the designated operator for the fieldwork. Primary objectives of the research program are to advance fundamental geological, geophysical and geochemical studies of the Mallik gas hydrate field and to undertake advanced production testing of a concentrated gas hydrate reservoir. Full-scale field experiments in the production well monitored the physical behavior of the hydrate deposits in response to depressurization and thermal stimulation. The observation wells facilitated cross-hole tomography and vertical seismic profile experiments (before and after production) as well as the measurement of in situ formation conditions. A wide- ranging science and engineering research program included the collection of gas-hydrate-bearing core samples and downhole geophysical logging. Laboratory and modeling studies undertaken during the field program, and subsequently as part of a post-field research program, will document the sedimentology, physical/petrophysical properties, geochemistry, geophysics, reservoir characteristics and production behavior of the Mallik gas hydrate accumulation. The research team, including some 100 participant scientists from over 20 institutes in 7 countries, expects to publish the scientific results in 2004.

Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2

PubMed Central

Wang, Jia; Cheng, Peng; Pavlyukov, Marat S.; Yu, Hai; Zhang, Zhuo; Kim, Sung-Hak; Minata, Mutsuko; Mohyeldin, Ahmed; Xie, Wanfu; Chen, Dongquan; Goidts, Violaine; Frett, Brendan; Hu, Wenhao; Li, Hongyu; Shin, Yong Jae; Lee, Yeri; Nam, Do-Hyun; Kornblum, Harley I.; Wang, Maode

2017-01-01

Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity–dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM. PMID:28737508

Identification of the underlying factor structure of the Derriford Appearance Scale 24

PubMed Central

Lawson, Victoria; White, Paul

2015-01-01

Background. The Derriford Appearance Scale24 (DAS24) is a widely used measure of distress and dysfunction in relation to self-consciousness of appearance. It has been used in clinical and research settings, and translated into numerous European and Asian languages. Hitherto, no study has conducted an analysis to determine the underlying factor structure of the scale. Methods. A large (n = 1,265) sample of community and hospital patients with a visible difference were recruited face to face or by post, and completed the DAS24. Results. A two factor solution was generated. An evaluation of the congruence of the factor solutions on each of the the hospital and the community samples using Tucker’s Coefficient of Congruence (rc = .979) and confirmatory factor analysis, which demonstrated a consistent factor structure. A main factor, general self consciousness (GSC), was represented by 18 items. Six items comprised a second factor, sexual and body self-consciousness (SBSC). The SBSC scale demonstrated greater sensitivity and specificity in identifying distress for sexually significant areas of the body. Discussion. The factor structure of the DAS24 facilitates a more nuanced interpretation of scores using this scale. Two conceptually and statistically coherent sub-scales were identified. The SBSC sub-scale offers a means of identifying distress and dysfunction around sexually significant areas of the body not previously possible with this scale. PMID:26157633

Magnetic hysteresis parameters and Day plot analysis to characterize diagenetic alteration in gas hydrate-bearing sediments

NASA Astrophysics Data System (ADS)

Enkin, Randolph J.; Baker, Judith; Nourgaliev, Danis; Iassonov, Pavel; Hamilton, Tark S.

2007-06-01

The J meter coercivity spectrometer is a machine capable of rapid and simple measurement of magnetic hysteresis, isothermal remanence acquisition and magnetic viscosity of rocks and sediments. The J meter was used to study a suite of samples collected from strata in the gas hydrate-bearing JAPEX/JNOC/GSC Mallik 5L-38 well (69.5°N, 134.6°W) in the Mackenzie Delta of the northwestern Canadian Arctic. The Day plot of magnetic hysteresis ratios for these samples is exotic in that the points do not plot along a hyperbola as is usually observed. Rather, they plot as a scatter which is shown to contour into vertical slices using coercivity field (HC) or saturation magnetization (JS), and horizontal slices using the relative quantity of superparamagnetism (JSPM/JS). Optical microscopy reveals that the magnetic minerals are detrital magnetite and authigenic greigite. Greigite is dominant in sands which in situ had >70% gas hydrate saturation and in silts in which gas hydrate growth was blocked by insufficient porosity. We infer that the silts were the accumulation sites for solutes which had been excluded from the pore waters in neighboring coarser-grained sediments during the course of gas hydrate formation. Consequently, we conclude that magnetic properties are related to gas hydrate-related processes, and as such, may have potential as a method of remote sensing for gas hydrate deposits.

Identification of the underlying factor structure of the Derriford Appearance Scale 24.

PubMed

Moss, Timothy P; Lawson, Victoria; White, Paul

2015-01-01

Background. The Derriford Appearance Scale24 (DAS24) is a widely used measure of distress and dysfunction in relation to self-consciousness of appearance. It has been used in clinical and research settings, and translated into numerous European and Asian languages. Hitherto, no study has conducted an analysis to determine the underlying factor structure of the scale. Methods. A large (n = 1,265) sample of community and hospital patients with a visible difference were recruited face to face or by post, and completed the DAS24. Results. A two factor solution was generated. An evaluation of the congruence of the factor solutions on each of the the hospital and the community samples using Tucker's Coefficient of Congruence (rc = .979) and confirmatory factor analysis, which demonstrated a consistent factor structure. A main factor, general self consciousness (GSC), was represented by 18 items. Six items comprised a second factor, sexual and body self-consciousness (SBSC). The SBSC scale demonstrated greater sensitivity and specificity in identifying distress for sexually significant areas of the body. Discussion. The factor structure of the DAS24 facilitates a more nuanced interpretation of scores using this scale. Two conceptually and statistically coherent sub-scales were identified. The SBSC sub-scale offers a means of identifying distress and dysfunction around sexually significant areas of the body not previously possible with this scale.

Antithrombotic agents intake prior to injury does not affect outcome after a traumatic brain injury in hospitalized elderly patients.

PubMed

Julien, Jessica; Alsideiri, Ghusn; Marcoux, Judith; Hasen, Mohammed; Correa, José A; Feyz, Mitra; Maleki, Mohammed; de Guise, Elaine

2017-04-01

The purpose of this study is to investigate the effect of risk factors including International Normalized Ratio (INR) as well as the Partial Thromboplastin Time (PTT) scores on several outcomes, including hospital length of stay (LOS) and The Extended Glasgow Outcome Scale (GOSE) following TBI in the elderly population. Data were retrospectively collected on patients (n=982) aged 65 and above who were admitted post TBI to the McGill University Health Centre-Montreal General Hospital from 2000 to 2011. Age, Injury Severity Score (ISS), Glasgow Coma Scale score (GCS), type of trauma (isolated TBI vs polytrauma including TBI), initial CT scan results according to the Marshall Classification and the INR and PTT scores and prescriptions of antiplatelet or anticoagulant agents (AP/AC) were collected. Results also indicated that age, ISS and GSC score have an effect on the GOSE score. We also found that taking AC/AP has an effect on GOSE outcome, but that this effects depends on PTT, with lower odds of a worse outcome for those taking AC/AP agents as the PTT value goes up. However, this effect only becomes significant as the PTT value reaches 60 and above. Age and injury severity rather than antithrombotic agent intake are associated with adverse acute outcome such as GOSE in hospitalized elderly TBI patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations.

PubMed

Cui, Daming; Sajan, Pandey; Shi, Jinlong; Shen, Yiwen; Wang, Ke; Deng, Xianyu; Zhou, Lin; Hu, Pingping; Gao, Liang

2017-04-11

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown. In vitro experiments showed that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration, and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H glioma and may help to identify therapeutic targets for the effective treatment of high-grade glioma.

MiR-148a increases glioma cell migration and invasion by downregulating GADD45A in human gliomas with IDH1 R132H mutations

PubMed Central

Shi, Jinlong; Shen, Yiwen; Wang, Ke; Deng, Xianyu; Zhou, Lin; Hu, Pingping; Gao, Liang

2017-01-01

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown. In vitro experiments showed that GADD45A negatively regulates IDH1R132H glioma cell proliferation, migration, and invasion, and neurosphere formation in IDH1R132H glioblastoma stem cells (GSC). In addition, a human orthotopic xenograft mouse model showed that GADD45A reduced tumorigenesis in vivo. Our findings demonstrated that miR-148a promotes glioma cell invasion and tumorigenesis by downregulating GADD45A. Our findings provide novel insights into how GADD45A is downregulated by miR-148a in IDH1R132H glioma and may help to identify therapeutic targets for the effective treatment of high-grade glioma. PMID:28445981

Enriching public descriptions of marine phages using the Genomic Standards Consortium MIGS standard

PubMed Central

Duhaime, Melissa Beth; Kottmann, Renzo; Field, Dawn; Glöckner, Frank Oliver

2011-01-01

In any sequencing project, the possible depth of comparative analysis is determined largely by the amount and quality of the accompanying contextual data. The structure, content, and storage of this contextual data should be standardized to ensure consistent coverage of all sequenced entities and facilitate comparisons. The Genomic Standards Consortium (GSC) has developed the “Minimum Information about Genome/Metagenome Sequences (MIGS/MIMS)” checklist for the description of genomes and here we annotate all 30 publicly available marine bacteriophage sequences to the MIGS standard. These annotations build on existing International Nucleotide Sequence Database Collaboration (INSDC) records, and confirm, as expected that current submissions lack most MIGS fields. MIGS fields were manually curated from the literature and placed in XML format as specified by the Genomic Contextual Data Markup Language (GCDML). These “machine-readable” reports were then analyzed to highlight patterns describing this collection of genomes. Completed reports are provided in GCDML. This work represents one step towards the annotation of our complete collection of genome sequences and shows the utility of capturing richer metadata along with raw sequences. PMID:21677864

HDF-EOS 5 Validator

NASA Technical Reports Server (NTRS)

Ullman, Richard; Bane, Bob; Yang, Jingli

2008-01-01

A computer program partly automates the task of determining whether an HDF-EOS 5 file is valid in that it conforms to specifications for such characteristics as attribute names, dimensionality of data products, and ranges of legal data values. ["HDF-EOS" and variants thereof are defined in "Converting EOS Data From HDF-EOS to netCDF" (GSC-15007-1), which is the first of several preceding articles in this issue of NASA Tech Briefs.] Previously, validity of a file was determined in a tedious and error-prone process in which a person examined human-readable dumps of data-file-format information. The present software helps a user to encode the specifications for an HDFEOS 5 file, and then inspects the file for conformity with the specifications: First, the user writes the specifications in Extensible Markup Language (XML) by use of a document type definition (DTD) that is part of the program. Next, the portion of the program (denoted the validator) that performs the inspection is executed, using, as inputs, the specifications in XML and the HDF-EOS 5 file to be validated. Finally, the user examines the output of the validator.

Interrogating heterogeneous compaction of meteoritic material at the mesoscale using analog experiments and numerical models

NASA Astrophysics Data System (ADS)

Derrick, James; Rutherford, Michael; Davison, Thomas; Chapman, David; Eakins, Daniel; Collins, Gareth

2017-06-01

Chondritic meteorites were lithified during solar system formation by compaction of bimodal mixtures of mm-scale, spherical, solidified melt droplets (chondrules) surrounded by a porous matrix of much finer grained dust. A possible compaction mechanism is low-velocity planetesimal collisions, which were common in the early solar system. Mesoscale numerical simulations of such impacts indicate heterogeneous compaction, with large porosity and temperature variations over sub-mm scales in the matrix and chondrules largely unaffected. In particular, compaction and heating are enhanced in front of the chondrule and suppressed in its wake. Such observations may provide a new tool for interpreting evidence for impact in meteorites. Here we present impact experiments that replicate compaction surrounding an individual chondrule using analog materials: Soda Lime glass beads/rods and 70% porous silica powder matrix (Sipernat). Real-time, X-ray imaging of the experiments, combined with mesoscale modelling, provides experimental confirmation of anisotropic matrix compaction surrounding individual chondrules, aligned with the shock direction. JGD is supported by EPSRC studentship funding; GSC are supported by STFC Grant ST/N000803/1.

Evaluating gold standard corpora against gene/protein tagging solutions and lexical resources

PubMed Central

2013-01-01

Motivation The identification of protein and gene names (PGNs) from the scientific literature requires semantic resources: Terminological and lexical resources deliver the term candidates into PGN tagging solutions and the gold standard corpora (GSC) train them to identify term parameters and contextual features. Ideally all three resources, i.e. corpora, lexica and taggers, cover the same domain knowledge, and thus support identification of the same types of PGNs and cover all of them. Unfortunately, none of the three serves as a predominant standard and for this reason it is worth exploring, how these three resources comply with each other. We systematically compare different PGN taggers against publicly available corpora and analyze the impact of the included lexical resource in their performance. In particular, we determine the performance gains through false positive filtering, which contributes to the disambiguation of identified PGNs. Results In general, machine learning approaches (ML-Tag) for PGN tagging show higher F1-measure performance against the BioCreative-II and Jnlpba GSCs (exact matching), whereas the lexicon based approaches (LexTag) in combination with disambiguation methods show better results on FsuPrge and PennBio. The ML-Tag solutions balance precision and recall, whereas the LexTag solutions have different precision and recall profiles at the same F1-measure across all corpora. Higher recall is achieved with larger lexical resources, which also introduce more noise (false positive results). The ML-Tag solutions certainly perform best, if the test corpus is from the same GSC as the training corpus. As expected, the false negative errors characterize the test corpora and – on the other hand – the profiles of the false positive mistakes characterize the tagging solutions. Lex-Tag solutions that are based on a large terminological resource in combination with false positive filtering produce better results, which, in addition, provide concept identifiers from a knowledge source in contrast to ML-Tag solutions. Conclusion The standard ML-Tag solutions achieve high performance, but not across all corpora, and thus should be trained using several different corpora to reduce possible biases. The LexTag solutions have different profiles for their precision and recall performance, but with similar F1-measure. This result is surprising and suggests that they cover a portion of the most common naming standards, but cope differently with the term variability across the corpora. The false positive filtering applied to LexTag solutions does improve the results by increasing their precision without compromising significantly their recall. The harmonisation of the annotation schemes in combination with standardized lexical resources in the tagging solutions will enable their comparability and will pave the way for a shared standard. PMID:24112383

Germline modification of domestic animals

PubMed Central

Tang, L.; González, R.; Dobrinski, I.

2016-01-01

Genetically-modified domestic animal models are of increasing significance in biomedical research and agriculture. As authentic ES cells derived from domestic animals are not yet available, the prevailing approaches for engineering genetic modifications in those animals are pronuclear microinjection and somatic cell nuclear transfer (SCNT, also known as cloning). Both pronuclear microinjection and SCNT are inefficient, costly, and time-consuming. In animals produced by pronuclear microinjection, the exogenous transgene is usually inserted randomly into the genome, which results in highly variable expression patterns and levels in different founders. Therefore, significant efforts are required to generate and screen multiple founders to obtain animals with optimal transgene expression. For SCNT, specific genetic modifications (both gain-of-function and loss-of-function) can be engineered and carefully selected in the somatic cell nucleus before nuclear transfer. SCNT has been used to generate a variety of genetically modified animals such as goats, pigs, sheep and cattle; however, animals resulting from SCNT frequently suffer from developmental abnormalities associated with incomplete nuclear reprogramming. Other strategies to generate genetically-modified animals rely on the use of the spermatozoon as a natural vector to introduce genetic material into the female gamete. This sperm mediated DNA transfer (SMGT) combined with intracytoplasmatic sperm injection (ICSI) has relatively high efficiency and allows the insertion of large DNA fragments, which, in turn, enhance proper gene expression. An approach currently being developed to complement SCNT for producing genetically modified animals is germ cell transplantation using genetically modified male germline stem cells (GSCs). This approach relies on the ability of GSCs that are genetically modified in vitro to colonize the recipient testis and produce donor derived sperm upon transplantation. As the genetic change is introduced into the male germ line just before the onset of spermatogenesis, the time required for the production of genetically modified sperm is significantly shorter using germ cell transplantation compared to cloning or embryonic stem (ES) cell based technology. Moreover, the GSC-mediated germline modification circumvents problems associated with embryo manipulation and nuclear reprogramming. Currently, engineering targeted mutations in domestic animals using GSCs remains a challenge as GSCs from those animals are difficult to maintain in vitro for an extended period of time. Recent advances in genome editing techniques such as Zinc-Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) greatly enhance the efficiency of engineering targeted genetic change in domestic animals as demonstrated by the generation of several gene knock-out pig and cattle models using those techniques. The potential of GSC-mediated germline modification in making targeted genetic modifications in domestic animal models will be maximized if those genome editing techniques can be applied in GSCs. PMID:27390591

Discovery of A Young L Dwarf Binary, SDSS J224953.47+004404.6AB

NASA Astrophysics Data System (ADS)

Allers, K. N.; Liu, Michael C.; Dupuy, Trent J.; Cushing, Michael C.

2010-05-01

We report discovery of a young 0farcs32 L dwarf binary, SDSS J2249+0044AB, found as the result of a Keck laser guide star adaptive optics imaging survey of young field brown dwarfs. Weak K I, Na I, and FeH features as well as strong VO absorption in the integrated-light J-band spectrum indicate a low surface gravity and hence young age for the system. From spatially resolved K-band spectra we determine spectral types of L3 ± 0.5 and L5 ± 1 for components A and B, respectively. SDSS J2249+0044A is spectrally very similar to G196-3B, an L3 companion to a young M2.5 field dwarf. Thus, we adopt 100 Myr (the age estimate of the G196-3 system) as the age of SDSS J2249+0044AB, but ages of 12-790 Myr are possible. By comparing our photometry to the absolute magnitudes of G196-3B, we estimate a distance to SDSS J2249+0044AB of 54 ± 16 pc and infer a projected separation of 17 ± 5 AU for the binary. Comparison of the luminosities to evolutionary models at an age of 100 Myr yields masses of 0.029 ± 0.006 and 0.022+0.006 -0.009 M sun for SDSS J2249+0044A and B, respectively. Over the possible ages of the system (12-790 Myr), the mass of SDSS J2249+0044A could range from 0.011 to 0.070 M sun and the mass of SDSS J2249+0044B could range from 0.009 to 0.065 M sun. Evolutionary models predict that either component could be burning deuterium, which could result in a mass ratio as low as 0.4, or alternatively, a reversal in the luminosities of the binary. We find a likely proper motion companion, GSC 00568-01752, which lies 48farcs9 away (a projected separation of 2600 AU) and has Sloan Digital Sky Survey and Two Micron All Sky Survey colors consistent with an early M dwarf. We calculate a photometric distance to GSC 00568-01752 of 53 ± 15 pc, in good agreement with our distance estimate for SDSS J2249+0044AB. The space motion of SDSS J2249+0044AB shows no obvious coincidence with known young moving groups, though radial velocity and parallax measurements are necessary to refine our analysis. The unusually red near-IR colors, young age, and low masses of the binary make it an important template for studying planetary-mass objects found by direct imaging surveys. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

PubMed Central

Chau, Johnnie; Kulnane, Laura Shapiro; Salz, Helen K.

2012-01-01

Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell state and to enter the differentiation pathway. Sxl encodes a female-specific RNA binding protein and in somatic cells serves as the developmental switch gene for somatic sex determination and X-chromosome dosage compensation. None of the known Sxl target genes are required for germline differentiation, leaving open the question of how Sxl promotes the transition from stem cell to committed daughter cell. We address the mechanism by which Sxl regulates this transition through the identification of nanos as one of its target genes. Previous studies have shown that Nanos protein is necessary for GSC self-renewal and is rapidly down-regulated in the daughter cells fated to differentiate in the adult ovary. We find that this dynamic expression pattern is limited to female germ cells and is under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is continuously expressed. Furthermore, this female-specific expression pattern is dependent on the presence of canonical Sxl binding sites located in the nanos 3′ untranslated region. These results, combined with the observation that nanos RNA associates with the Sxl protein in ovarian extracts and loss and gain of function studies, suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional down-regulation of nanos expression. These findings connect sexual identity to the stem cell self-renewal/differentiation decision and highlight the importance of posttranscriptional gene regulatory networks in controlling stem cell behavior. PMID:22645327

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis.

PubMed

Chau, Johnnie; Kulnane, Laura Shapiro; Salz, Helen K

2012-06-12

Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell state and to enter the differentiation pathway. Sxl encodes a female-specific RNA binding protein and in somatic cells serves as the developmental switch gene for somatic sex determination and X-chromosome dosage compensation. None of the known Sxl target genes are required for germline differentiation, leaving open the question of how Sxl promotes the transition from stem cell to committed daughter cell. We address the mechanism by which Sxl regulates this transition through the identification of nanos as one of its target genes. Previous studies have shown that Nanos protein is necessary for GSC self-renewal and is rapidly down-regulated in the daughter cells fated to differentiate in the adult ovary. We find that this dynamic expression pattern is limited to female germ cells and is under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is continuously expressed. Furthermore, this female-specific expression pattern is dependent on the presence of canonical Sxl binding sites located in the nanos 3' untranslated region. These results, combined with the observation that nanos RNA associates with the Sxl protein in ovarian extracts and loss and gain of function studies, suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional down-regulation of nanos expression. These findings connect sexual identity to the stem cell self-renewal/differentiation decision and highlight the importance of posttranscriptional gene regulatory networks in controlling stem cell behavior.

Isolation and characteristics of CD133‑/A2B5+ and CD133‑/A2B5‑ cells from the SHG139s cell line.

PubMed

Han, Yong; Wang, Hangzhou; Huang, Yulun; Cheng, Zhe; Sun, Ting; Chen, Guilin; Xie, Xueshun; Zhou, Youxin; Du, Ziwei

2015-12-01

In glioma tissues, there are small cell populations with the capability of sustaining tumor formation. These cells are referred to as glioma stem cells (GSCs). However, the presence of subpopulations of GSCs, and the differences between each subpopulation remain to be fully elucidated. In the present study, CD133‑/A2B5‑ and CD133‑/A2B5+ cells from the SHG139 GSC cell line (SHG139s) were isolated using magnetic‑activated cell sorting. Following xenografting into nude mice, the two isolated subpopulations generated tumors. The characteristics of the two subpopulations were investigated extensively, and it was found that the two exhibited cancer stem cell characteristics. These cells expressed stem cell markers, exhibited a neurosphere‑like appearance, and were found to exhibit self‑renewal and multipotency capabilities. Subsequently, the self‑renewal and proliferation abilities of the two subpopulations were compared. It was found that the A2B5‑ cells had a higher proliferative index and a higher self‑renewal ability, compared with the A2B5+ cells. In addition, the A2B5‑ cells exhibited increased angiogenic ability. However, the invasion ability of the A2B5+ cells was higher than that of the A2B5‑ cells. Taken together, the results of the present study suggested that there are different cell subpopulations in GSCs, and each subpopulation has its own properties.

Major- and Trace-Element Concentrations in Soils from Northern California: Results from the Geochemical Landscapes Project Pilot Study

USGS Publications Warehouse

Morrison, Jean M.; Goldhaber, Martin B.; Holloway, JoAnn M.; Smith, David B.

2008-01-01

In 2004, the U.S. Geological Survey (USGS), the Geological Survey of Canada (GSC), and the Mexican Geological Survey (Servicio Geologico Mexicano, or SGM) initiated pilot studies in preparation for a soil geochemical survey of North America called the Geochemical Landscapes Project. The purpose of this project is to provide a better understanding of the variability in chemical composition of soils in North America. The data produced by this survey will be used to construct baseline geochemical maps for regions within the continent. Two initial pilot studies were conducted: (1) a continental-scale study involving a north-south and east-west transect across North America and (2) a regional-scale study. The pilot studies were intended to test and refine sample design, sampling protocols, and field logistics for the full continental soils geochemical survey. Smith and others (2005) reported the results from the continental-scale pilot study. The regional-scale California study was designed to represent more detailed, higher resolution geochemical investigations in a region of particular interest that was identified from the low-sample-density continental-scale survey. A 20,000-km2 area of northern California (fig. 1), representing a wide variety of topography, climate, and ecoregions, was chosen for the regional-scale pilot study. This study area also contains diverse geology and soil types and supports a wide range of land uses including agriculture in the Sacramento Valley, forested areas in portions of the Sierra Nevada, and urban/suburban centers such as Sacramento, Davis, and Stockton. Also of interest are potential effects on soil geochemistry from historical hard rock and placer gold mining in the foothills of the Sierra Nevada, historical mercury mining in the Coast Range, and mining of base-metal sulfide deposits in the Klamath Mountains to the north. This report presents the major- and trace-element concentrations from the regional-scale soil geochemical survey in northern California.

Drosophila male and female germline stem cell niches require the nuclear lamina protein Otefin.

PubMed

Barton, Lacy J; Lovander, Kaylee E; Pinto, Belinda S; Geyer, Pamela K

2016-07-01

The nuclear lamina is an extensive protein network that underlies the inner nuclear envelope. This network includes the LAP2-emerin-MAN1-domain (LEM-D) protein family, proteins that share an association with the chromatin binding protein Barrier-to-autointegration factor (BAF). Loss of individual LEM-D proteins causes progressive, tissue-restricted diseases, known as laminopathies. Mechanisms associated with laminopathies are not yet understood. Here we present our studies of one of the Drosophila nuclear lamina LEM-D proteins, Otefin (Ote), a homologue of emerin. Previous studies have shown that Ote is autonomously required for the survival of female germline stem cells (GSCs). We demonstrate that Ote is also required for survival of somatic cells in the ovarian niche, with loss of Ote causing a decrease in cap cell number and altered signal transduction. We show germ cell-restricted expression of Ote rescues these defects, revealing a non-autonomous function for Ote in niche maintenance and emphasizing that GSCs contribute to the maintenance of their own niches. Further, we investigate the requirement of Ote in the male fertility. We show that ote mutant males become prematurely sterile as they age. Parallel to observations in females, this sterility is associated with GSC loss and changes in somatic cells of the niche, phenotypes that are largely rescued by germ cell-restricted Ote expression. Taken together, our studies demonstrate that Ote is required autonomously for survival of two stem cell populations, as well as non-autonomously for maintenance of two somatic niches. Finally, our data add to growing evidence that LEM-D proteins have critical roles in stem cell survival and tissue homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Short-term stability of sleep and heart rate variability in good sleepers and patients with insomnia: for some measures, one night is enough.

PubMed

Israel, Benjamin; Buysse, Daniel J; Krafty, Robert T; Begley, Amy; Miewald, Jean; Hall, Martica

2012-09-01

Quantify the short-term stability of multiple indices of sleep and nocturnal physiology in good sleeper controls and primary insomnia patients. Intra-class correlation coefficients (ICC) were used to quantify the short-term stability of study outcomes. Sleep laboratory. Fifty-four adults with primary insomnia (PI) and 22 good sleeper controls (GSC). Visually scored sleep outcomes included indices of sleep duration, continuity, and architecture. Quantitative EEG outcomes included power in the delta, theta, alpha, sigma, and beta bands during NREM sleep. Power spectral analysis was used to estimate high-frequency heart rate variability (HRV) and the ratio of low- to high-frequency HRV power during NREM and REM sleep. With the exception of percent stage 3+4 sleep; visually scored sleep outcomes did not exhibit short-term stability across study nights. Most QEEG outcomes demonstrated short-term stability in both groups. Although power in the beta band was stable in the PI group (ICC = 0.75), it tended to be less stable in GSCs (ICC = 0.55). Both measures of cardiac autonomic tone exhibited short-term stability in GSCs and PIs during NREM and REM sleep. Most QEEG bandwidths and HRV during sleep show high short-term stability in good sleepers and patients with insomnia alike. One night of data is, thus, sufficient to derive reliable estimates of these outcomes in studies focused on group differences or correlates of QEEG and/or HRV. In contrast, one night of data is unlikely to generate reliable estimates of PSG-assessed sleep duration, continuity or architecture, with the exception of slow wave sleep.

miR-544 Regulates Dairy Goat Male Germline Stem Cell Self-Renewal via Targeting PLZF.

PubMed

Song, Wencong; Mu, Hailong; Wu, Jiang; Liao, Mingzhi; Zhu, Haijing; Zheng, Liming; He, Xin; Niu, Bowen; Zhai, Yuanxin; Bai, Chunling; Lei, Anmin; Li, Guangpeng; Hua, Jinlian

2015-10-01

The balance between the self-renewal and differentiation of male germline stem cells (mGSCs) is critical for the initiation and maintenance of mammalian spermatogenesis. The promyelocytic leukemia zinc finger (PLZF), a zinc finger protein, is a critical factor for maintaining the self-renewal of mGSCs, so, evaluation of the PLZF pathway in mGSCs may provide a deeper insight into mammalian spermatogenesis. miRNA was also an important regulating factor for the self-renewal and differentiation of mGSCs; however, there is currently no data indicating that which miRNA regulate the self-renewal and differentiation of mGSCs via PLZF. Here, we predicted the prospective miRNA targeting to PLZF using the online Bioinformatics database-Targetscan, and performed an analysis of the dual-luciferase recombinant vector, psiCHCEKTM-2-PLZF-3'UTR. miR-544 mimics (miR-544m), miR-544 inhibitors (miR-544i), Control (NC, scrambled oligonucleotides transfection), pPLZF-IRES2-EGFP or PLZF siRNA were transfected into mGSCs; the cells proliferation was evaluated by BRDU incorporation assay and flow cytometry, and the mGSC marker, GFRa1, PLZF, KIT, DAZL, and VASA expression were analyzed by RT-qPCR, immunofluorescence and Western blot. The results showed that miR-544 regulates dairy goat male germline stem cell self-renewal via targeting PLZF. Our study identifies a new regulatory pathway for PLZF and expands upon the PLZF regulatory network in mGSCs. © 2015 Wiley Periodicals, Inc.

miR-135b suppresses tumorigenesis in glioblastoma stem-like cells impairing proliferation, migration and self-renewal.

PubMed

Lulli, Valentina; Buccarelli, Mariachiara; Martini, Maurizio; Signore, Michele; Biffoni, Mauro; Giannetti, Stefano; Morgante, Liliana; Marziali, Giovanna; Ilari, Ramona; Pagliuca, Alfredo; Larocca, Luigi Maria; De Maria, Ruggero; Pallini, Roberto; Ricci-Vitiani, Lucia

2015-11-10

Glioblastoma multiforme (GBM) is the most common and fatal malignant adult primary brain tumor. Currently, the overall prognosis for GBM patients remains poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs) contribute to the pathogenesis of various types of tumor, including GBM. In this study we analyzed the expression of a panel of miRNAs, which are known to be differentially expressed by the brain and GBM tumor, in a collection of patient-derived GBM stem-like cells (GSCs). Notably, the average expression level of miR-135b, was the most downregulated compared to its normal counterpart, suggesting a potential role as anti-oncogene.Restoration of miR-135b in GSCs significantly decreased proliferation, migration and clonogenic abilities. More importantly, miR-135b restoration was able to significantly reduce brain infiltration in mouse models of GBM obtained by intracerebral injection of GSC lines. We identified ADAM12 and confirmed SMAD5 and GSK3β as miR-135b targets and potential mediators of its effects. The whole transcriptome analysis ascertained that the expression of miR-135b downmodulated additional genes driving key pathways in GBM survival and infiltration capabilities.Our results identify a critical role of miR-135b in the regulation of GBM development, suggesting that miR-135b might act as a tumor-suppressor factor and thus providing a potential candidate for the treatment of GBM patients.

Here Be Dragons: Characterization of ACS/WFC Scattered Light Anomalies

NASA Astrophysics Data System (ADS)

Porterfield, B.; Coe, D.; Gonzaga, S.; Anderson, J.; Grogin, N.

2016-11-01

We present a study characterizing scattered light anomalies that occur near the edges of Advanced Camera for Surveys (ACS) Wide Field Channel (WFC) images. We inspected all 8,573 full-frame ACS/WFC raw images with exposure times longer than 350 seconds obtained in the F606W and F814W filters from 2002 to October 2013. We visually identified two particular scattered light artifacts known as "dragon's breath" and edge glow. Using the 2MASS point source catalog and Hubble Guide Star Catalog (GSC II), we identified the stars that caused these artifacts. The stars are all located in narrow bands ( 3" across) just outside the ACS/WFC field of view (2" - 16" away). We provide a map of these risky areas around the ACS/WFC detectors - users should avoid positioning bright stars in these regions when designing ACS/WFC imaging observations. We also provide interactive webpages which display all the image artifacts we identified, allowing users to see examples of the severity of artifacts they might expect for a given stellar magnitude at a given position relative to the ACS/WFC field of view. On average, 10th (18th) magnitude stars produce artifacts about 1,000 (100) pixels long. But the severity of these artifacts can vary strongly with small positional shifts (∼ 1"). The results are similar for both filters (F606W and F814W) when expressed in total fluence, or flux multiplied by exposure time.

Feature-oriented regional modeling and simulations in the Gulf of Maine and Georges Bank

NASA Astrophysics Data System (ADS)

Gangopadhyay, Avijit; Robinson, Allan R.; Haley, Patrick J.; Leslie, Wayne G.; Lozano, Carlos J.; Bisagni, James J.; Yu, Zhitao

2003-03-01

The multiscale synoptic circulation system in the Gulf of Maine and Georges Bank (GOMGB) region is presented using a feature-oriented approach. Prevalent synoptic circulation structures, or 'features', are identified from previous observational studies. These features include the buoyancy-driven Maine Coastal Current, the Georges Bank anticyclonic frontal circulation system, the basin-scale cyclonic gyres (Jordan, Georges and Wilkinson), the deep inflow through the Northeast Channel (NEC), the shallow outflow via the Great South Channel (GSC), and the shelf-slope front (SSF). Their synoptic water-mass ( T- S) structures are characterized and parameterized in a generalized formulation to develop temperature-salinity feature models. A synoptic initialization scheme for feature-oriented regional modeling and simulation (FORMS) of the circulation in the coastal-to-deep region of the GOMGB system is then developed. First, the temperature and salinity feature-model profiles are placed on a regional circulation template and then objectively analyzed with appropriate background climatology in the coastal region. Furthermore, these fields are melded with adjacent deep-ocean regional circulation (Gulf Stream Meander and Ring region) along and across the SSF. These initialization fields are then used for dynamical simulations via the primitive equation model. Simulation results are analyzed to calibrate the multiparameter feature-oriented modeling system. Experimental short-term synoptic simulations are presented for multiple resolutions in different regions with and without atmospheric forcing. The presented 'generic and portable' methodology demonstrates the potential of applying similar FORMS in many other regions of the Global Coastal Ocean.

An Explanation of the Very Low Radio Flux of Young Planet-mass Companions

NASA Astrophysics Data System (ADS)

Wu, Ya-Lin; Close, Laird M.; Eisner, Josh A.; Sheehan, Patrick D.

2017-12-01

We report Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum upper limits for five planetary-mass companions DH Tau B, CT Cha B, GSC 6214-210 B, 1RXS 1609 B, and GQ Lup B. Our survey, together with other ALMA studies, have yielded null results for disks around young planet-mass companions and placed stringent dust mass upper limits, typically less than 0.1 M ⊕, when assuming dust continuum is optically thin. Such low-mass gas/dust content can lead to a disk lifetime estimate (from accretion rates) much shorter than the age of the system. To alleviate this timescale discrepancy, we suggest that disks around wide companions might be very compact and optically thick in order to sustain a few Myr of accretion, yet have very weak (sub)millimeter flux so as to still be elusive to ALMA. Our order-of-magnitude estimate shows that compact optically thick disks might be smaller than 1000 R Jup and only emit ∼μJy of flux in the (sub)millimeter, but their average temperature can be higher than that of circumstellar disks. The high disk temperature could impede satellite formation, but it also suggests that mid- to far-infrared might be more favorable than radio wavelengths to characterize disk properties. Finally, the compact disk size might imply that dynamical encounters between the companion and the star, or any other scatterers in the system, play a role in the formation of planetary-mass companions.

GRODY - GAMMA RAY OBSERVATORY DYNAMICS SIMULATOR IN ADA

NASA Technical Reports Server (NTRS)

Stark, M.

1994-01-01

Analysts use a dynamics simulator to test the attitude control system algorithms used by a satellite. The simulator must simulate the hardware, dynamics, and environment of the particular spacecraft and provide user services which enable the analyst to conduct experiments. Researchers at Goddard's Flight Dynamics Division developed GRODY alongside GROSS (GSC-13147), a FORTRAN simulator which performs the same functions, in a case study to assess the feasibility and effectiveness of the Ada programming language for flight dynamics software development. They used popular object-oriented design techniques to link the simulator's design with its function. GRODY is designed for analysts familiar with spacecraft attitude analysis. The program supports maneuver planning as well as analytical testing and evaluation of the attitude determination and control system used on board the Gamma Ray Observatory (GRO) satellite. GRODY simulates the GRO on-board computer and Control Processor Electronics. The analyst/user sets up and controls the simulation. GRODY allows the analyst to check and update parameter values and ground commands, obtain simulation status displays, interrupt the simulation, analyze previous runs, and obtain printed output of simulation runs. The video terminal screen display allows visibility of command sequences, full-screen display and modification of parameters using input fields, and verification of all input data. Data input available for modification includes alignment and performance parameters for all attitude hardware, simulation control parameters which determine simulation scheduling and simulator output, initial conditions, and on-board computer commands. GRODY generates eight types of output: simulation results data set, analysis report, parameter report, simulation report, status display, plots, diagnostic output (which helps the user trace any problems that have occurred during a simulation), and a permanent log of all runs and errors. The analyst can send results output in graphical or tabular form to a terminal, disk, or hardcopy device, and can choose to have any or all items plotted against time or against each other. Goddard researchers developed GRODY on a VAX 8600 running VMS version 4.0. For near real time performance, GRODY requires a VAX at least as powerful as a model 8600 running VMS 4.0 or a later version. To use GRODY, the VAX needs an Ada Compilation System (ACS), Code Management System (CMS), and 1200K memory. GRODY is written in Ada and FORTRAN.

Improvement in Recursive Hierarchical Segmentation of Data

NASA Technical Reports Server (NTRS)

Tilton, James C.

2006-01-01

A further modification has been made in the algorithm and implementing software reported in Modified Recursive Hierarchical Segmentation of Data (GSC- 14681-1), NASA Tech Briefs, Vol. 30, No. 6 (June 2006), page 51. That software performs recursive hierarchical segmentation of data having spatial characteristics (e.g., spectral-image data). The output of a prior version of the software contained artifacts, including spurious segmentation-image regions bounded by processing-window edges. The modification for suppressing the artifacts, mentioned in the cited article, was addition of a subroutine that analyzes data in the vicinities of seams to find pairs of regions that tend to lie adjacent to each other on opposite sides of the seams. Within each such pair, pixels in one region that are more similar to pixels in the other region are reassigned to the other region. The present modification provides for a parameter ranging from 0 to 1 for controlling the relative priority of merges between spatially adjacent and spatially non-adjacent regions. At 1, spatially-adjacent-/spatially- non-adjacent-region merges have equal priority. At 0, only spatially-adjacent-region merges (no spectral clustering) are allowed. Between 0 and 1, spatially-adjacent- region merges have priority over spatially- non-adjacent ones.

Implementation of a Wavefront-Sensing Algorithm

NASA Technical Reports Server (NTRS)

Smith, Jeffrey S.; Dean, Bruce; Aronstein, David

2013-01-01

A computer program has been written as a unique implementation of an image-based wavefront-sensing algorithm reported in "Iterative-Transform Phase Retrieval Using Adaptive Diversity" (GSC-14879-1), NASA Tech Briefs, Vol. 31, No. 4 (April 2007), page 32. This software was originally intended for application to the James Webb Space Telescope, but is also applicable to other segmented-mirror telescopes. The software is capable of determining optical-wavefront information using, as input, a variable number of irradiance measurements collected in defocus planes about the best focal position. The software also uses input of the geometrical definition of the telescope exit pupil (otherwise denoted the pupil mask) to identify the locations of the segments of the primary telescope mirror. From the irradiance data and mask information, the software calculates an estimate of the optical wavefront (a measure of performance) of the telescope generally and across each primary mirror segment specifically. The software is capable of generating irradiance data, wavefront estimates, and basis functions for the full telescope and for each primary-mirror segment. Optionally, each of these pieces of information can be measured or computed outside of the software and incorporated during execution of the software.

Astrometric Improvements for the USNO-A Catalog

NASA Astrophysics Data System (ADS)

Monet, D.

1997-12-01

The USNO-A1.0 catalog (Monet et al. 1996; 10 CD-ROMs; USNO) contains astrometric and photometric information for 488,006,860 objects. Since its compilation, many areas for improvement have been identified. This paper presents a progress report on the implementation of these improvements and discusses the schedule for the compilation of USNO-A2.0. The most significant improvement will be the incorporation of the International Celestial Reference Frame through the adoption of the ACT Catalog (Urban et al. in preparation; CD-ROM; USNO). (The ACT uses data from the Astrographic Catalog to compute proper motions for stars found in the Hipparcos and Tycho catalogs.) In addition to providing the realization of the astrometric reference frame, the ACT catalog contains a high enough source density to allow for a GSC-free derivation of the systematic components of the astrometric distortions found in the Schmidt telescopes that took the survey plates, and for a determination of the magnitude terms for the Palomar Schmidt using the data from the scans of the UJ plates. Other topics include the development of a numerical refocusing technique to improve the quality of existing scans, and the lessons being learned from the scanning of the Lick Northern Proper Motion survey plates.

Glioblastoma stem cells exploit the αvβ8 integrin-TGFβ1 signaling axis to drive tumor initiation and progression

PubMed Central

Guerrero, PA; Tchaicha, JH; Chen, Z; Morales, JE; McCarty, N; Wang, Q; Sulman, EP; Fuller, G; Lang, FF; Rao, G; McCarty, JH

2018-01-01

Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin αvβ8 and its latent transforming growth factor β1 (TGFβ1) protein ligand have central roles in promoting niche co-option and GBM initiation. αvβ8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of β8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that αvβ8 integrin regulates tumor development, in part, by driving TGFβ1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the αvβ8 integrin-TGFβ1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM. PMID:28783169

Evaluation of the Air Quality Monitor's Performance on the International Space Station

NASA Technical Reports Server (NTRS)

Limero, Thomas; Reese, Eric; Ballard, Ken; Durham, Tamara

2010-01-01

The Air Quality Monitor (AQM) was flown to the International Space Station (ISS) as an experiment to evaluate its potential to replace the aging Volatile Organic Analyzer (VOA), which ceased operations in August 2009. The AQM (Figure 1) is a small gas chromatography/differential mobility spectrometer (GC/DMS) manufactured by Sionex. Data was presented at last year s ISIMS conference that detailed the preparation of the AQM for flight, including instrument calibration. Furthermore, initial AQM data was compared to VOA results from simultaneous runs of the two instruments. Although comparison with VOA data provided a measure of confidence in the AQM performance, it is the comparison with results from simultaneously acquired air samples (grab sample containers-GSCs) that will define the success (or failure) of the AQM performance. This paper will update the progress in the AQM investigation by comparing AQM data to results from the analyses of GSC samples, returned from ISS. Additionally, a couple of example will illustrate the AQM s ability to detect disruptions in the spacecraft s air quality. Discussion will also focus upon a few unexpected issues that have arisen and how these will be a addressed in the final operational unit now being built.

Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients.

PubMed

Assem, Mostafa; Kamal, Samia; Sabry, Dina; Soliman, Nadia; Aly, Riham M

2018-02-15

Stem cells have recently received great interest as potential therapeutics alternative for a variety of diseases. The oral and maxillofacial region, in particular, encompasses a variety of distinctive mesenchymal (MSC) populations and is characterized by a potent multilineage differentiation capacity. In this report, we aimed to investigate the effect of diabetes on the proliferation potential of stem cells isolated from controlled diabetic patients (type 2) and healthy individuals. The proliferation rate of gingival and periodontal derived stem cells isolated from diabetic & healthy individuals were compared using MTT Assay. Expression levels of Survivin in isolated stem cells from all groups were measured by qRt - PCR. There was a significantly positive correlation between proliferation rate and expression of Survivin in all groups which sheds light on the importance of Survivin as a reliable indicator of proliferation. The expression of Survivin further confirmed the proliferation results from MTT Assay where the expression of stem cells from non - diabetic individuals was higher than diabetic patients. Taking together all the results, it could be concluded that PDLSC and GSC are promising candidates for autologous regenerative therapy due to their ease of accessibility in addition to their high proliferative rates.

Conceptualizing a Genomics Software Institute (GSI)

PubMed Central

Gilbert, Jack A.; Catlett, Charlie; Desai, Narayan; Knight, Rob; White, Owen; Robbins, Robert; Sankaran, Rajesh; Sansone, Susanna-Assunta; Field, Dawn; Meyer, Folker

2012-01-01

Microbial ecology has been enhanced greatly by the ongoing ‘omics revolution, bringing half the world's biomass and most of its biodiversity into analytical view for the first time; indeed, it feels almost like the invention of the microscope and the discovery of the new world at the same time. With major microbial ecology research efforts accumulating prodigious quantities of sequence, protein, and metabolite data, we are now poised to address environmental microbial research at macro scales, and to begin to characterize and understand the dimensions of microbial biodiversity on the planet. What is currently impeding progress is the need for a framework within which the research community can develop, exchange and discuss predictive ecosystem models that describe the biodiversity and functional interactions. Such a framework must encompass data and metadata transparency and interoperation; data and results validation, curation, and search; application programming interfaces for modeling and analysis tools; and human and technical processes and services necessary to ensure broad adoption. Here we discuss the need for focused community interaction to augment and deepen established community efforts, beginning with the Genomic Standards Consortium (GSC), to create a science-driven strategic plan for a Genomic Software Institute (GSI). PMID:22675605

Assessment of Air Quality in the Shuttle and International Space Station (ISS) Based on Samples Returned by STS-100 at the Conclusion of 6A

NASA Technical Reports Server (NTRS)

James, John T.

2001-01-01

The toxicological assessment of air samples returned at the end of the STS-100 (6A) flight to the ISS is reported. ISS air samples were taken in March and April 2001 from the Service Module, FGB, and U.S. Laboratory using grab sample canisters (GSCs) and/or formaldehyde badges. An unplanned "first-entry" sample of the MPLM2 (multipurpose logistics module) atmosphere was taken with a GSC, and preflight and end-of-mission samples were obtained from Endeavour using GSCs. Analytical methods have not changed from earlier reports, and all quality control measures were met for the data presented herein. The two general criteria used to assess air quality are the total-non-methane-volatile organic hydrocarbons (NMVOCs) and the total T-value (minus the CO2 and formaldehyde contribution). Because of the Freon 218 (octafluoropropane, OFP) leak, its contribution to the NMVOC is indicated in brackets. When comparing the NMVOC values with the 25 mg/cubic m guideline, the OFP contributions should be subtracted. Control of atmospheric alcohols is important to the water recovery system engineers, hence total alcohols were also assessed in each sample.

Increased prognostic accuracy of TBI when a brain electrical activity biomarker is added to loss of consciousness (LOC).

PubMed

Hack, Dallas; Huff, J Stephen; Curley, Kenneth; Naunheim, Roseanne; Ghosh Dastidar, Samanwoy; Prichep, Leslie S

2017-07-01

Extremely high accuracy for predicting CT+ traumatic brain injury (TBI) using a quantitative EEG (QEEG) based multivariate classification algorithm was demonstrated in an independent validation trial, in Emergency Department (ED) patients, using an easy to use handheld device. This study compares the predictive power using that algorithm (which includes LOC and amnesia), to the predictive power of LOC alone or LOC plus traumatic amnesia. ED patients 18-85years presenting within 72h of closed head injury, with GSC 12-15, were study candidates. 680 patients with known absence or presence of LOC were enrolled (145 CT+ and 535 CT- patients). 5-10min of eyes closed EEG was acquired using the Ahead 300 handheld device, from frontal and frontotemporal regions. The same classification algorithm methodology was used for both the EEG based and the LOC based algorithms. Predictive power was evaluated using area under the ROC curve (AUC) and odds ratios. The QEEG based classification algorithm demonstrated significant improvement in predictive power compared with LOC alone, both in improved AUC (83% improvement) and odds ratio (increase from 4.65 to 16.22). Adding RGA and/or PTA to LOC was not improved over LOC alone. Rapid triage of TBI relies on strong initial predictors. Addition of an electrophysiological based marker was shown to outperform report of LOC alone or LOC plus amnesia, in determining risk of an intracranial bleed. In addition, ease of use at point-of-care, non-invasive, and rapid result using such technology suggests significant value added to standard clinical prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

Total and ionized plasma magnesium concentrations in children after traumatic brain injury.

PubMed

Mendez, Donna Reyes; Corbett, Ronald; Macias, Charles; Laptook, Abbot

2005-03-01

This study examined 1) whether plasma total Mg (TMg) and ionized Mg (IMg) concentrations in children are reduced by traumatic brain injury (TBI) and 2) whether the extent of reduction correlates with severity of trauma assessed by the Glasgow Coma Scale (GSC) score. This was a prospective cohort study of 98 pediatric patients who had TBI and were admitted through the emergency department. A GCS score was assigned and blood was obtained upon presentation and 24 h later. Plasma was analyzed for TMg and IMg. Patients were grouped into three categories-GCS scores 13-15, 8-12, and <8-to designate mild (n=21), moderate (n=37), and severe (n=40) TBI, respectively. Blood was obtained from 50 healthy children before elective surgery as controls. Control subjects had a TMg and an IMg of 0.94 +/- 0.08 and 0.550 +/- 0.06 mM. TBI patients had an initial TMg and IMg of 0.83 +/- 0.09 and 0.520 +/- 0.05 mM, respectively. Initial TMg for mild, moderate, and severe TBI subgroups (0.87 +/- 0.16, 0.81 +/- 0.15, and 0.83 +/- 0.14 mM, respectively) was reduced from control subjects (p <0.01). IMg was reduced only in the severe TBI subgroup (0.516 +/- 0.07 mM; p=0.016). Twenty-four hours later, TMg remained lower than in control subjects for all subgroups of TBI; however, IMg normalized. TBI in children is associated with a reduction in TMg, whereas IMg decreased only with severe TBI. IMg returned to control values by 24 h despite a continued lower TMg, suggesting mechanisms to maintain IMg. Changes in plasma IMg may serve as a marker for TBI but only over a limited time interval.

Bimodal Long-lasting Components in Short Gamma-Ray Bursts: Promising Electromagnetic Counterparts to Neutron Star Binary Mergers

NASA Astrophysics Data System (ADS)

Kisaka, Shota; Ioka, Kunihito; Sakamoto, Takanori

2017-09-01

Long-lasting emission of short gamma-ray bursts (GRBs) is crucial to reveal the physical origin of the central engine as well as to detect electromagnetic (EM) counterparts to gravitational waves (GWs) from neutron star binary mergers. We investigate 65 X-ray light curves of short GRBs, which is six times more than previous studies, by combining both Swift/BAT and XRT data. The light curves are found to consist of two distinct components at >5σ with bimodal distributions of luminosity and duration, I.e., extended (with a timescale of ≲103 s) and plateau emission (with a timescale of ≳103 s), which are likely the central engine activities, but not afterglows. The extended emission has an isotropic energy comparable to the prompt emission, while the plateau emission has ˜0.01-1 times this energy. Half (50%) of our sample has both components, while the other half is consistent with having both components. This leads us to conjecture that almost all short GRBs have both the extended and plateau emission. The long-lasting emission can be explained by the jets from black holes with fallback ejecta, and could power macronovae (or kilonovae) like GRB 130603B and GRB 160821B. Based on the observed properties, we quantify the detectability of EM counterparts to GWs, including the plateau emission scattered to the off-axis angle, with CALET/HXM, INTEGRAL/SPI-ACS, Fermi/GBM, MAXI/GSC, Swift/BAT, XRT, the future ISS-Lobster/WFI, Einstein Probe/WXT, and eROSITA.

Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma.

PubMed

Pangeni, Rajendra P; Zhang, Zhou; Alvarez, Angel A; Wan, Xuechao; Sastry, Namratha; Lu, Songjian; Shi, Taiping; Huang, Tianzhi; Lei, Charles X; James, C David; Kessler, John A; Brennan, Cameron W; Nakano, Ichiro; Lu, Xinghua; Hu, Bo; Zhang, Wei; Cheng, Shi-Yuan

2018-06-21

Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes. We hypothesized that these DNA methylation signatures correlate with gene expression and are uniquely associated either with only GSCs or only GBM bulk tumors. Additional methylation signatures may be commonly associated with both GSCs and GBM bulk tumors, i.e., common to non-stem-like and stem-like tumor cell populations and correlating with the clinical prognosis of glioma patients. We analyzed Illumina 450K methylation array and expression data from a panel of 23 patient-derived GSCs. We referenced these results with The Cancer Genome Atlas (TCGA) GBM datasets to generate methylomic and transcriptomic signatures for GSCs and GBM bulk tumors of each transcriptomically pre-defined tumor subtype. Survival analyses were carried out for these signature genes using publicly available datasets, including from TCGA. We report that DNA methylation signatures in proneural and mesenchymal tumor subtypes are either unique to GSCs, unique to GBM bulk tumors, or common to both. Further, dysregulated DNA methylation correlates with gene expression and clinical prognoses. Additionally, many previously identified transcriptionally-regulated markers are also dysregulated due to DNA methylation. The subtype-specific DNA methylation signatures described in this study could be useful for refining GBM sub-classification, improving prognostic accuracy, and making therapeutic decisions.

Small G protein Rac GTPases regulate the maintenance of glioblastoma stem-like cells in vitro and in vivo.

PubMed

Lai, Yun-Ju; Tsai, Jui-Cheng; Tseng, Ying-Ting; Wu, Meng-Shih; Liu, Wen-Shan; Lam, Hoi-Ian; Yu, Jei-Hwa; Nozell, Susan E; Benveniste, Etty N

2017-03-14

Glioblastoma is the most common and aggressive malignant brain tumor in adults. The existence of glioblastoma stem cells (GSCs) or stem-like cells (stemloids) may account for its invasiveness and high recurrence. Rac proteins belong to the Rho small GTPase subfamily which regulates cell movement, proliferation, and survival. To investigate whether Rac proteins can serve as therapeutic targets for glioblastoma, especially for GSCs or stemloids, we examined the potential roles of Rac1, Rac2 and Rac3 on the properties of tumorspheres derived from glioblastoma cell lines. Tumorspheres are thought to be glioblastoma stem-like cells. We showed that Rac proteins promote the STAT3 and ERK activation and enhance cell proliferation and colony formation of glioblastoma stem-like cells. Knockdown of Rac proteins reduces the expression of GSC markers, such as CD133 and Sox2. The in vivo effects of Rac proteins in glioblastoma were further studied in zebrafish and in the mouse xenotransplantation model. Knocking-down Rac proteins abolished the angiogenesis effect induced by the injected tumorspheres in zebrafish model. In the CD133+-U373-tumorsphere xenotransplanted mouse model, suppression of Rac proteins decreased the incidence of tumor formation and inhibited the tumor growth. Moreover, knockdown of Rac proteins reduced the sphere forming efficiency of cells derived from these tumors. In conclusion, not only Rac1 but also Rac2 and 3 are important for glioblastoma tumorigenesis and can serve as the potential therapeutic targets against glioblastoma and its stem-like cells.

Small G protein Rac GTPases regulate the maintenance of glioblastoma stem-like cells in vitro and in vivo

PubMed Central

Lai, Yun-Ju; Tsai, Jui-Cheng; Tseng, Ying-Ting; Wu, Meng-Shih; Liu, Wen-Shan; Lam, Hoi-Ian; Yu, Jei-Hwa; Nozell, Susan E.; Benveniste, Etty N.

2017-01-01

Glioblastoma is the most common and aggressive malignant brain tumor in adults. The existence of glioblastoma stem cells (GSCs) or stem–like cells (stemloids) may account for its invasiveness and high recurrence. Rac proteins belong to the Rho small GTPase subfamily which regulates cell movement, proliferation, and survival. To investigate whether Rac proteins can serve as therapeutic targets for glioblastoma, especially for GSCs or stemloids, we examined the potential roles of Rac1, Rac2 and Rac3 on the properties of tumorspheres derived from glioblastoma cell lines. Tumorspheres are thought to be glioblastoma stem-like cells. We showed that Rac proteins promote the STAT3 and ERK activation and enhance cell proliferation and colony formation of glioblastoma stem-like cells. Knockdown of Rac proteins reduces the expression of GSC markers, such as CD133 and Sox2. The in vivo effects of Rac proteins in glioblastoma were further studied in zebrafish and in the mouse xenotransplantation model. Knocking-down Rac proteins abolished the angiogenesis effect induced by the injected tumorspheres in zebrafish model. In the CD133+-U373-tumorsphere xenotransplanted mouse model, suppression of Rac proteins decreased the incidence of tumor formation and inhibited the tumor growth. Moreover, knockdown of Rac proteins reduced the sphere forming efficiency of cells derived from these tumors. In conclusion, not only Rac1 but also Rac2 and 3 are important for glioblastoma tumorigenesis and can serve as the potential therapeutic targets against glioblastoma and its stem-like cells. PMID:28160553

Bimodal Long-lasting Components in Short Gamma-Ray Bursts: Promising Electromagnetic Counterparts to Neutron Star Binary Mergers

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

Kisaka, Shota; Sakamoto, Takanori; Ioka, Kunihito, E-mail: kisaka@phys.aoyama.ac.jp, E-mail: tsakamoto@phys.aoyama.ac.jp, E-mail: kunihito.ioka@yukawa.kyoto-u.ac.jp

Long-lasting emission of short gamma-ray bursts (GRBs) is crucial to reveal the physical origin of the central engine as well as to detect electromagnetic (EM) counterparts to gravitational waves (GWs) from neutron star binary mergers. We investigate 65 X-ray light curves of short GRBs, which is six times more than previous studies, by combining both Swift /BAT and XRT data. The light curves are found to consist of two distinct components at >5 σ with bimodal distributions of luminosity and duration, i.e., extended (with a timescale of ≲10{sup 3} s) and plateau emission (with a timescale of ≳10{sup 3} s),more » which are likely the central engine activities, but not afterglows. The extended emission has an isotropic energy comparable to the prompt emission, while the plateau emission has ∼0.01–1 times this energy. Half (50%) of our sample has both components, while the other half is consistent with having both components. This leads us to conjecture that almost all short GRBs have both the extended and plateau emission. The long-lasting emission can be explained by the jets from black holes with fallback ejecta, and could power macronovae (or kilonovae) like GRB 130603B and GRB 160821B. Based on the observed properties, we quantify the detectability of EM counterparts to GWs, including the plateau emission scattered to the off-axis angle, with CALET /HXM, INTEGRAL /SPI-ACS, Fermi /GBM, MAXI /GSC, Swift /BAT, XRT, the future ISS-Lobster /WFI, Einstein Probe /WXT, and eROSITA .« less

Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

PubMed Central

Ning, Jianfang; Wakimoto, Hiroaki

2014-01-01

Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) “armed” viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma. PMID:24999342

Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth

PubMed Central

Hamerlik, Petra; Lathia, Justin D.; Rasmussen, Rikke; Wu, Qiulian; Bartkova, Jirina; Lee, MyungHee; Moudry, Pavel; Bartek, Jiri; Fischer, Walter; Lukas, Jiri

2012-01-01

Although vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) is traditionally regarded as an endothelial cell protein, evidence suggests that VEGFRs may be expressed by cancer cells. Glioblastoma multiforme (GBM) is a lethal cancer characterized by florid vascularization and aberrantly elevated VEGF. Antiangiogenic therapy with the humanized VEGF antibody bevacizumab reduces GBM tumor growth; however, the clinical benefits are transient and invariably followed by tumor recurrence. In this study, we show that VEGFR2 is preferentially expressed on the cell surface of the CD133+ human glioma stem-like cells (GSCs), whose viability, self-renewal, and tumorigenicity rely, at least in part, on signaling through the VEGF-VEGFR2–Neuropilin-1 (NRP1) axis. We find that the limited impact of bevacizumab-mediated VEGF blockage may reflect ongoing autocrine signaling through VEGF–VEGFR2–NRP1, which is associated with VEGFR2–NRP1 recycling and a pool of active VEGFR2 within a cytosolic compartment of a subset of human GBM cells. Whereas bevacizumab failed to inhibit prosurvival effects of VEGFR2-mediated signaling, GSC viability under unperturbed or radiation-evoked stress conditions was attenuated by direct inhibition of VEGFR2 tyrosine kinase activity and/or shRNA-mediated knockdown of VEGFR2 or NRP1. We propose that direct inhibition of VEGFR2 kinase may block the highly dynamic VEGF–VEGFR2–NRP1 pathway and inspire a GBM treatment strategy to complement the currently prevalent ligand neutralization approach. PMID:22393126

WE-G-BRF-09: Force- and Image-Adaptive Strategies for Robotised Placement of 4D Ultrasound Probes

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

Kuhlemann, I; Graduate School for Computing in Life Science, University of Luebeck, Luebeck; Bruder, R

2014-06-15

Purpose: To allow continuous acquisition of high quality 4D ultrasound images for non-invasive live tracking of tumours for IGRT, image- and force-adaptive strategies for robotised placement of 4D ultrasound probes are developed and evaluated. Methods: The developed robotised ultrasound system is based on a 6-axes industrial robot (adept Viper s850) carrying a 4D ultrasound transducer with a mounted force-torque sensor. The force-adaptive placement strategies include probe position control using artificial potential fields and contact pressure regulation by a PD controller strategy. The basis for live target tracking is a continuous minimum contact pressure to ensure good image quality and highmore » patient comfort. This contact pressure can be significantly disturbed by respiratory movements and has to be compensated. All measurements were performed on human subjects under realistic conditions. When performing cardiac ultrasound, rib- and lung shadows are a common source of interference and can disrupt the tracking. To ensure continuous tracking, these artefacts had to be detected to automatically realign the probe. The detection is realised by multiple algorithms based on entropy calculations as well as a determination of the image quality. Results: Through active contact pressure regulation it was possible to reduce the variance of the contact pressure by 89.79% despite respiratory motion of the chest. The results regarding the image processing clearly demonstrate the feasibility to detect image artefacts like rib shadows in real-time. Conclusion: In all cases, it was possible to stabilise the image quality by active contact pressure control and automatically detected image artefacts. This fact enables the possibility to compensate for such interferences by realigning the probe and thus continuously optimising the ultrasound images. This is a huge step towards fully automated transducer positioning and opens the possibility for stable target tracking in ultrasoundguided radiation therapy requiring contact pressure of 5–10 N. This work was supported by the Graduate School for Computing in Medicine and Life Sciences funded by Germany's Excellence Initiative [DFG GSC 235/1].« less

An Occultation by Saturn's Rings on 1991 October 2-3 October 2-3 Observed with the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Elliot, J. L.; Bosh, A. S.; Cooke, M. L.; Bless, R. C.; Nelson, M. J.; Percival, J. W.; Taylor, M. J.; Dolan, J. F.; Robinson, E. L.; Van Citters, G. W.

1993-01-01

An occultation of the star GSC 6323-01396 (V = 11.9) by Saturn's rings was observed with the High-Speed Photometer on the Hubble Space Telescope (HST) on 1991 October 2-3. This occultation occurred when Saturn was near a stationary point, so the apparent motion of Saturn relative to the star was dominated by the HST orbital motion (8 km/s). Data were recorded simultaneously at effective wavelengths of 3200 and 7500 A, with an integration time of 0.15 s. Fifteen segments of occultation data, totaling 6.8 h, were recorded in 13 successive orbits during the 20.0 h interval from UTC 1991 October 2, 19:35 until UTC 1991 October 3, 15:35. Occultations by 43 different features throughout the classical rings were unambiguously identified in the light curve, with a second occultation by 24 of them occurring due to spacecraft orbital parallax during this extremely slow event. Occultation times for features currently presumed circular were measured and employed in a geometrical model for the rings. This model, relating the observed occultation times to feature radii and longitudes, is presented here and is used in a least-squares fit for the pole direction and radius scale of Saturn's ring system.

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

Johnson, John Asher; Morton, T. D.; Winn, J. N.

We report the discovery of HAT-P-30b, a transiting exoplanet orbiting the V = 10.419 dwarf star GSC 0208-00722. The planet has a period P = 2.810595 {+-} 0.000005 days, transit epoch T{sub c} = 2455456.46561 {+-} 0.00037 (BJD), and transit duration 0.0887 {+-} 0.0015 days. The host star has a mass of 1.24 {+-} 0.04 M{sub sun}, radius of 1.21 {+-} 0.05 R{sub sun}, effective temperature of 6304 {+-} 88 K, and metallicity [Fe/H] = +0.13 {+-} 0.08. The planetary companion has a mass of 0.711 {+-} 0.028 M{sub J} and radius of 1.340 {+-} 0.065 R{sub J} yielding amore » mean density of 0.37 {+-} 0.05 g cm{sup -3}. We also present radial velocity measurements that were obtained throughout a transit that exhibit the Rossiter-McLaughlin effect. By modeling this effect, we measure an angle of {lambda} = 73.{sup 0}5 {+-} 9.{sup 0}0 between the sky projections of the planet's orbit normal and the star's spin axis. HAT-P-30b represents another example of a close-in planet on a highly tilted orbit, and conforms to the previously noted pattern that tilted orbits are more common around stars with T{sub eff*} {approx}> 6250 K.« less

Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6.

PubMed

Xi, Zhuo; Wang, Ping; Xue, Yixue; Shang, Chao; Liu, Xiaobai; Ma, Jun; Li, Zhiqing; Li, Zhen; Bao, Min; Liu, Yunhui

2017-04-11

Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis. MiR-29a directly inhibited the expression of Quaking gene isoform 6 (QKI-6) by binding to its 3'-UTR, and thus inhibited GSC malignant behavior. In addition, Wilms' tumor 1-associating protein (WTAP) was identified as a downstream target of QKI-6. Overexpression of miR-29a in GSCs inhibited expression of WTAP and suppressed both phosphoinositide 3-kinase/AKT and extracellular signal-related kinase pathways by downregulating QKI-6, thereby inhibiting cell proliferation, migration, and invasion but promoting apoptosis. We have characterized a novel miR-29a/QKI-6/WTAP axis in GSCs, which may provide theoretical support for the treatment of glioblastoma with miR-29a agomirs.

A confirmatory factor analysis of the Beck Depression Inventory-II in end-stage renal disease patients.

PubMed

Chilcot, Joseph; Norton, Sam; Wellsted, David; Almond, Mike; Davenport, Andrew; Farrington, Ken

2011-09-01

We sought to examine several competing factor structures of the Beck Depression Inventory-II (BDI) in a sample of patients with End-Stage Renal Disease (ESRD), in which setting the factor structure is poorly defined, though depression symptoms are common. In addition, demographic and clinical correlates of the identified factors were examined. The BDI was administered to clinical sample of 460 ESRD patients attending 4 UK renal centres. Competing models of the factor structure of the BDI were evaluated using confirmatory factor analysis. The best fitting model consisted of general depression factor that accounted for 81% of the common variance between all items along with orthogonal cognitive and somatic factors (G-S-C model, CFI=.983, TLI=.979, RMSEA=.037), which explained 8% and 9% of the common variance, respectively. Age, diabetes, and ethnicity were significantly related to the cognitive factor, whereas albumin, dialysis adequacy, and ethnicity were related to the somatic factor. No demographic or clinical variable was associated with the general factor. The general-factor model provides the best fitting and conceptually most acceptable interpretation of the BDI. Furthermore, the cognitive and somatic factors appear to be related to specific demographic and clinical factors. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Chemotherapeutic Drugs: DNA Damage and Repair in Glioblastoma.

PubMed

Annovazzi, Laura; Mellai, Marta; Schiffer, Davide

2017-05-26

Despite improvements in therapeutic strategies, glioblastoma (GB) remains one of the most lethal cancers. The presence of the blood-brain barrier, the infiltrative nature of the tumor and several resistance mechanisms account for the failure of current treatments. Distinct DNA repair pathways can neutralize the cytotoxicity of chemo- and radio-therapeutic agents, driving resistance and tumor relapse. It seems that a subpopulation of stem-like cells, indicated as glioma stem cells (GSCs), is responsible for tumor initiation, maintenance and recurrence and they appear to be more resistant owing to their enhanced DNA repair capacity. Recently, attention has been focused on the pivotal role of the DNA damage response (DDR) in tumorigenesis and in the modulation of therapeutic treatment effects. In this review, we try to summarize the knowledge concerning the main molecular mechanisms involved in the removal of genotoxic lesions caused by alkylating agents, emphasizing the role of GSCs. Beside their increased DNA repair capacity in comparison with non-stem tumor cells, GSCs show a constitutive checkpoint expression that enables them to survive to treatments in a quiescent, non-proliferative state. The targeted inhibition of checkpoint/repair factors of DDR can contribute to eradicate the GSC population and can have a great potential therapeutic impact aiming at sensitizing malignant gliomas to treatments, improving the overall survival of patients.

A Poised Chromatin Platform for TGF-[beta] Access to Master Regulators

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

Xi, Qiaoran; Wang, Zhanxin; Zaromytidou, Alexia-Ileana

2012-02-07

Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-{beta} signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compactingmore » factor HP1, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.« less

Variability Analysis based on POSS1/POSS2 Photometry

NASA Astrophysics Data System (ADS)

Mickaelian, Areg M.; Sarkissian, Alain; Sinamyan, Parandzem K.

2012-04-01

We introduce accurate magnitudes as combined calculations from catalogues based on accurate measurements of POSS1- and POSS2-epoch plates. The photometric accuracy of various catalogues was established, and statistical weights for each of them have been calculated. To achieve the best possible magnitudes, we used weighted averaging of data from APM, MAPS, USNO-A2.0, USNO-B1.0 (for POSS1-epoch), and USNO-B1.0 and GSC 2.3.2 (for POSS2-epoch) catalogues. The r.m.s. accuracy of magnitudes achieved for POSS1 is 0.184 in B and 0.173 mag in R, or 0.138 in B and 0.128 in R for POSS2. By adopting those new magnitudes we examined the First Byurakan Survey (FBS) of blue stellar objects for variability, and uncovered 336 probable and possible variables among 1103 objects with POSS2-POSS1 >= 3σ of the errors, including 161 highly probable variables. We have developed methods to control and exclude accidental errors for any survey. We compared and combined our results with those given in Northern Sky Variability Survey (NSVS) database, and obtained firm candidates for variability. By such an approach it will be possible to conduct investigations of variability for large numbers of objects.

Broadband Seismic Studies at the Mallik Gas Hydrate Research Well

NASA Astrophysics Data System (ADS)

Sun, L. F.; Huang, J.; Lyons-Thomas, P.; Qian, W.; Milkereit, B.; Schmitt, D. R.

2005-12-01

The JAPEX/JNOC/GSC et al. Mallik 3L-38, 4L-38 and 5L-38 scientific wells were drilled in the MacKenzie Delta, NWT, Canada in early 2002 primarily for carrying out initial tests of the feasibility of producing methane gas from the large gas hydrate deposits there [1]. As part of this study, high resolution seismic profiles, a pseudo-3D single fold seismic volume and broadband (8~180Hz) multi-offset vertical seismic profiles (VSP) were acquired at the Mallik site. Here, we provide details on the acquisition program, present the results of the 2D field profile, and discuss the potential implications of these observations for the structure of the permafrost and gas hydrate zones. These zones have long been problematic in seismic imaging due to the lateral heterogeneities. Conventional seismic data processing usually assume a stratified, weak-contrast elastic earth model. However, in permafrost and gas hydrate zones this approximation often becomes invalid. This leads to seismic wave scattering caused by multi-scale perturbation of elastic properties. A 3D viscoelastic finite difference modeling algorithm was employed to simulate wave propagation in a medium with strong contrast. Parameters in this modeling analysis are based on the borehole geophysical log data. In addition, an uncorrelated Vibroseis VSP data set was studied to investigate frequency-dependent absorption and velocity dispersion. Our results indicate that scattering and velocity dispersion are important for a better understanding of attenuation mechanisms in heterogeneous permafrost and gas hydrate zones. [1] Dallimore, S.R., Collett, T.S., Uchida, T., and Weber, M., 2005, Overview of the science program for the Mallik 2002 Gas Hydrate Production Research Well Program; in Scientific Results from Mallik 2002 Gas Hydrate production Research Well Program, MacKenzie Delta, Northwest Territories, Canada, (ed.) S.R. Dallimore and T.S. Collett; Geological Survey of Canada, Bulletin 585, in press.

Seafloor Volcanic and Structural Features Adjacent to the 90deg 50'N Transform - Galapagos Spreading Center: Clues for Understanding Plate Boundary Kinematics and Lithospheric Melting Processes (Invited)

NASA Astrophysics Data System (ADS)

Fornari, D. J.; Soule, S.; Harpp, K. S.; Mittelstaedt, E. L.; Geist, D.; Kurz, M. D.; R/v Melville Mv1007 Cruise Scientific Party

2010-12-01

High-resolution EM122 multibeam and MR-1 sidescan sonar data collected over a wide area of seafloor west and east of the 90deg 50’N transform along the Galapagos Spreading Center (GSC) reveal seafloor morpho-structural fabric created along this intermediate spreading plate boundary. In concert with geochemical and geophysical data collected during the cruise, these data will be used to help unravel the kinematics of hotspot-ridge interactions in the northern Galapagos. West of the transform, the seafloor is dominated by three prominent NW-SE trending seamount lineaments, each ~20-30 km wide, including the prominent Wolf-Darwin Lineament (WDL) as well as two other smaller volcanic chains east of the WDL, which are oriented along intermediate trends that become more subparallel to the N-S trend of the transform from west to east. This suggests a possible strong controlling influence of the transform on the orientation of lithospheric fractures involved in supplying magmas to the volcanic centers. Interestingly, each seamount lineament west of the transform appears to have nascent volcanoes nucleating immediately south of the GSC axis at locations that mark along-axis discontinuities of the spreading center, suggesting ridge-related magmatic focusing is also influencing crustal generation on the Nazca plate in this region. The tectonized terrain associated with the transform is 60 km wide, whereas the transform valley is only 20 km wide. The northern 40 km of the transform has a well-defined linear shear zone and bounding faults. The southern 50 km of the transform are characterized by a wide zone of extensive oblique shear structures that trend NW-SE. Within this zone are numerous small volcanic cones and ridges that decorate the margins and axis of the transform domain. The structural evolution of the transform appears to be undergoing a transition along its length with intra-transform volcanism in the south and more normal shear in the north, however the tectonic imprint of the oblique structures is observed along nearly all of the length of the transform out to 15-20 km from the margins of the transform valley. Terrain east of the transform is markedly different in morphological character and structural elements. A series of five, generally E-W ridges, some of which display clear volcanic constructional terrain, extend from the eastern margin of the oblique fabric associated with the transform domain. Some of these E-W features are linked by N-S structures, creating a general patchwork pattern of seafloor that is unlike any we have observed at well-mapped ridge-transform intersections at fast and intermediate spreading mid-ocean ridges. The terrain bears some similarities to structures developed at microplates. We also note that this region lies at the southwestern extremity of the Cocos Ridge, an aseismic ridge that has undergone a complex history of volcanic and tectonic construction associated with hotspot magmatism and ridge jumps.

Sedimentology and Permafrost Characteristics of Pingo-Like Features (PLFs) from the Beaufort Sea shelf, NWT, Canada

NASA Astrophysics Data System (ADS)

Medioli, B. E.; Dallimore, S. R.; Nixon, F. M.; Dallimore, A.; Blasco, S.; Paull, C. K.; McLaughlin, F.; Ussler, W.; Davies, E.

2004-12-01

Pingo-like features (PLFs) are rounded positive relief features commonly found on Beaufort Sea shelf, NWT. PLFs occur in water depths from 20 to 200m, are typically a few hundred meters in diameter and rise 10 to 35m above the seafloor. In the fall of 2003, an MBARI-USGS-GSC-DFO coring and geophysical study was undertaken of a number of PLFs. The crests, flanks and moats of 8 PLFs, as well as background shelf sites, were vibra-cored. Upon recovery, core temperatures of moat sediments ranged from 2.0 to -0.5 deg C and no ice bonding was observed. Sediments consisted of dark-olive-grey to black muds with shells. Sedimentary structures were rare with some finely laminated to finely-color-banded beds. Intense bioturbation, in situ marine shells and a lack of terriginous macrofossils suggest moat sediments were deposited in a shallow coastal environment. In some instances, a down core grain size coarsening was observed with higher organic content suggesting a gradational environment towards more lagoonal conditions. Core temperatures from the 8 PLFs were 0 to -1.7 deg C, significantly colder than the moat sediments. Ice-bonded permafrost was encountered within 1m of the seabed with visible ice content up to 40% by volume. Several ice-bonded intervals were preserved frozen for detailed investigation in the lab. The observed ground ice in the cores was quite unique when compared with visible ice forms commonly seen in regional terrestrial sections. The ice gave the core a vuggy texture with individual ice-filled vugs 10 to 200 mm3. Vugs were typically flattened to ovoid. When thawed, the ice produced excess water resulting in a very soft texture. In many cases the vuggy texture was maintained with sediment voids forming where the ice was. PLF crest sediments were massive silty clays with clayey silts and muddy fine sand interbeds. They generally lack sedimentary structures, although this may have been due to sediment structure loss upon thawing. The background seafloor sediments consisted of unfrozen, massive silty sands and sandy silts and were distinct from the crest and moat sediments. In several cores, a sharp transition was noted to well-sorted sands. This lower unit may represent a transgressed terrestrial sequence. Research continues to determine the origin of the PLFs and quantify the role of permafrost and ice formation.

[The opportunity to use combined stem cells transplantation for haemopoesis activation in the old and mature laboratory animals under the conditions of ionizing radiation].

PubMed

Grebnev, D U

2014-01-01

The objective of this work was to study the influence of combined transplantation of stem cells (multypotent mesenchimal stromal and hem poetic stem cells) on the haemopoesis of old and mature laboratory animals under the condition of ionizing radiation. The experiments were conducted on 48 white male mice with the body weight of 30 g, age of 3-4 months, and 48 male mice of 3 years of age and body mass of 50 g. The experiments for obtaining the MMSC and HSC cultures were conducted on 16 laboratory animals: female mice of 3-4 months of age and body mass of 30 g., 18 days gestation period. The control group was formed by the animals not under the ionizing radiation. The experimental group animals got the dose of 4 Gr. These animals also got MMSC and HSC mixture intravenously in the doses of 6 mln. c/kg. and 330 thousand cell/kg prospectively. The control group animals got the 0.9% NaCl - 0.2 ml. intravenously. The infusions were made 1 hour after radiation once. As the result of the experiment it was shown that under physiological conditions combined transplantation brings the erithropoesis activation, under the ionizing radiation conditions it brings the erythroid and granulocytopoesis activation. More over the combined MMSC and HSC transplantation gives cytoprotective action on the myeloid tissue due to decrease of cyto genically changed cells in the mature animals under the condition of ionizing radiation, but in the old animals this effect can be seen even under physiological condition. Conclusions: Combined transplantation of MMSC and GSC can be used in the mature and old laboratory animals under the conditions of ionising radiation for the haemopoesis activation.

Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

PubMed

Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

2015-01-01

Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

The DNA-PK Inhibitor VX-984 Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and as Orthotopic Xenografts.

PubMed

Timme, Cindy R; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J

2018-06-01

Radiotherapy is a primary treatment modality for glioblastomas (GBM). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSB), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation. In a similar concentration-dependent manner, VX-984 treatment enhanced the radiosensitivity of each GBM cell line as defined by clonogenic analysis. As determined by γH2AX expression and neutral comet analyses, VX-984 inhibited the repair of radiation-induced DNA double-strand break in U251 and NSC11 GBM cells, suggesting that the VX-984-induced radiosensitization is mediated by an inhibition of DNA repair. Extending these results to an in vivo model, treatment of mice with VX-984 inhibited radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts, indicating that this compound crosses the blood-brain tumor barrier at sufficient concentrations. For mice bearing U251 or NSC11 brain tumors, VX-984 treatment alone had no significant effect on overall survival; radiation alone increased survival. The survival of mice receiving the combination protocol was significantly increased as compared with control and as compared with radiation alone. These results indicate that VX-984 enhances the radiosensitivity of brain tumor xenografts and suggest that it may be of benefit in the therapeutic management of GBM. Mol Cancer Ther; 17(6); 1207-16. ©2018 AACR . ©2018 American Association for Cancer Research.

Effect of GSK-3 inhibitor on the proliferation of multipotent male germ line stem cells (mGSCs) derived from goat testis.

PubMed

Zhu, H; Liu, C; Sun, J; Li, M; Hua, J

2012-06-01

The glycogen synthase kinase 3 (GSK3) inhibitor, 6-bromoindirubin-3'-oxime (BIO), is a key regulator of many signaling pathways to maintain pluripotency of human and mouse embryonic stem cells (ESCs). However, the effect of BIO on derivation of dairy goat male germline stem cells (mGSCs) remains unclear. The objectives of this study were to investigate whether BIO influences derivation of dairy goat mGSCs. Dairy goat mGSCs were cultured in mTeSR containing BIO medium and its effects on the proliferation ability of goat mGSCs (derived from goats ≤2 mo of age) were evaluated by 5-Bromo-2-deoxyuridine (BrdU) incorporation and alkaline phosphatase (AP) staining. Furthermore, its effects on maintenance of the undifferentiated state of mGSCs in late passages of cultures, as well as the capacity of mGSCs to differentiate into embryoid bodies (EBs) were examined. The presence of BIO increased the mitosis index and the number of AP positive colonies, as well as expression of pluripotent markers, Oct4, Nanog, Sox2, C-myc, Klf4, E-cadherin, and the proliferative markers, Pcna and C-myc. In contrast, there was no significant change in expression of apoptosis markers, P53, P21 and cyclin-related genes (Cyclin A, CDK2, Cyclin D1), as determined by RT-PCR analysis. When mGSCs were cultured in mTeSR medium containing BIO, EBs were formed, which were capable of further differentiating into various cell types found in the three embryonic germ layers, as determined by immunofluorescence and/or histologic staining. In conclusion, adding BIO to cultures BIO significantly promoted establishment of goat mGSC colonies and maintained their undifferentiated state. Copyright © 2012 Elsevier Inc. All rights reserved.

HAT-P-17b,c: A TRANSITING, ECCENTRIC, HOT SATURN AND A LONG-PERIOD, COLD JUPITER

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

Howard, A. W.; Marcy, G. W.; Bakos, G. A.

2012-04-20

We report the discovery of HAT-P-17b,c, a multi-planet system with an inner transiting planet in a short-period, eccentric orbit and an outer planet in a 4.4 yr, nearly circular orbit. The inner planet, HAT-P-17b, transits the bright V = 10.54 early K dwarf star GSC 2717-00417, with an orbital period P = 10.338523 {+-} 0.000009 days, orbital eccentricity e = 0.342 {+-} 0.006, transit epoch T{sub c} = 2454801.16943 {+-} 0.00020 (BJD: barycentric Julian dates throughout the paper are calculated from Coordinated Universal Time (UTC)), and transit duration 0.1690 {+-} 0.0009 days. HAT-P-17b has a mass of 0.534 {+-} 0.018more » M{sub J} and radius of 1.010 {+-} 0.029 R{sub J} yielding a mean density of 0.64 {+-} 0.05 g cm{sup -3}. This planet has a relatively low equilibrium temperature in the range 780-927 K, making it an attractive target for follow-up spectroscopic studies. The outer planet, HAT-P-17c, has a significantly longer orbital period P{sub 2} = 1610 {+-} 20 days and a minimum mass m{sub 2}sin i{sub 2} = 1.31{sup +0.18}{sub -0.15} M{sub J}. The orbital inclination of HAT-P-17c is unknown as transits have not been observed and may not be present. The host star has a mass of 0.86 {+-} 0.04 M{sub Sun }, radius of 0.84 {+-} 0.02 R{sub Sun }, effective temperature 5246 {+-} 80 K, and metallicity [Fe/H] = 0.00 {+-} 0.08. HAT-P-17 is the second multi-planet system detected from ground-based transit surveys.« less

Efficient programming of human eye conjunctiva-derived induced pluripotent stem (ECiPS) cells into definitive endoderm-like cells.

PubMed

Massumi, Mohammad; Hoveizi, Elham; Baktash, Parvaneh; Hooti, Abdollah; Ghazizadeh, Leili; Nadri, Samad; Pourasgari, Farzaneh; Hajarizadeh, Athena; Soleimani, Masoud; Nabiuni, Mohammad; Khorramizadeh, Mohammad R

2014-03-10

Due to pluripotency of induced pluripotent stem (iPS) cells, and the lack of immunological incompatibility and ethical issues, iPS cells have been considered as an invaluable cell source for future cell replacement therapy. This study was aimed first at establishment of novel iPS cells, ECiPS, which directly reprogrammed from human Eye Conjunctiva-derived Mesenchymal Stem Cells (EC-MSCs); second, comparing the inductive effects of Wnt3a/Activin A biomolecules to IDE1 small molecule in derivation of definitive endoderm (DE) from the ECiPS cells. To that end, first, the EC-MSCs were transduced by SOKM-expressing lentiviruses and characterized for endogenous expression of embryonic markers Then the established ECiPS cells were induced to DE formation by Wnt3a/Activin A or IDE1. Quantification of GSC, Sox17 and Foxa2 expression, as DE-specific markers, in both mRNA and protein levels revealed that induction of ECiPS cells by either Wnt3a/Activin A or IDE1 could enhance the expression level of the genes; however the levels of increase were higher in Wnt3a/Activin A induced ECiPS-EBs than IDE1 induced cells. Furthermore, the flow cytometry analyses showed no synergistic effect between Activin A and Wnt3a to derive DE-like cells from ECiPS cells. The comparative findings suggest that although both Wnt3a/Activin A signaling and IDE1 molecule could be used for differentiation of iPS into DE cells, the DE-inducing effect of Wnt3a/Activin A was statistically higher than IDE1. Copyright © 2014 Elsevier Inc. All rights reserved.

A Novel Oncolytic Herpes Simplex Virus that Synergizes with Phosphatidylinositol 3-Kinase/Akt Pathway Inhibitors to Target Glioblastoma Stem Cells

PubMed Central

Kanai, Ryuichi; Wakimoto, Hiroaki; Martuza, Robert L.; Rabkin, Samuel D.

2011-01-01

Purpose To develop a new oncolytic herpes simplex virus (oHSV) for glioblastoma therapy that will be effective in glioblastoma stem cells (GSCs), an important and untargeted component of glioblastoma. One approach to enhance oHSV efficacy is by combination with other therapeutic modalities. Experimental design MG18L, containing a US3 deletion and an inactivating LacZ insertion in UL39, was constructed for the treatment of brain tumors. Safety was evaluated after intracerebral injection in HSV-susceptible mice. The efficacy of MG18L in human GSCs and glioma cell lines in vitro was compared to other oHSVs, alone or in combination with PI3K/Akt inhibitors (LY294002, triciribine, GDC-0941, BEZ235). Cytotoxic interactions between MG18L and PI3K/Akt inhibitors were determined using Chou-Talalay analysis. In vivo efficacy studies were performed using a clinically relevant mouse model of GSC-derived glioblastoma. Results MG18L was severely neuroattenuated in mice, replicated well in GSCs, and had anti-glioblastoma activity in vivo. PI3K/Akt inhibitors displayed significant but variable anti-proliferative activities in GSCs, while their combination with MG18L synergized in killing GSCs and glioma lines, but not human astrocytes, through enhanced induction of apoptosis. Importantly, synergy was independent of inhibitor sensitivity. In vivo, the combination of MG18L and LY294002 significantly prolonged survival of mice, as compared to either agent alone, achieving 50% long-term survival in glioblastoma-bearing mice. Conclusions This study establishes a novel therapeutic strategy: oHSV manipulation of critical oncogenic pathways to sensitize cancer cells to molecularly-targeted drugs. MG18L is a promising agent for the treatment of glioblastoma, being especially effective when combined with PI3K/Akt pathway-targeted agents. PMID:21505062

KCTD2, an adaptor of Cullin3 E3 ubiquitin ligase, suppresses gliomagenesis by destabilizing c-Myc

PubMed Central

Kim, Eun-Jung; Kim, Sung-Hak; Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-01-01

Cullin3 E3 ubiquitin ligase ubiquitinates a wide range of substrates through substrate-specific adaptors Bric-a-brac, Tramtrack, and Broad complex (BTB) domain proteins. These E3 ubiquitin ligase complexes are involved in diverse cellular functions. Our recent study demonstrated that decreased Cullin3 expression induces glioma initiation and correlates with poor prognosis of patients with malignant glioma. However, the substrate recognition mechanism associated with tumorigenesis is not completely understood. Through yeast two-hybrid screening, we identified potassium channel tetramerization domain-containing 2 (KCTD2) as a BTB domain protein that binds to Cullin3. The interaction of Cullin3 and KCTD2 was verified using immunoprecipitation and immunofluorescence. Of interest, KCTD2 expression was markedly decreased in patient-derived glioma stem cells (GSCs) compared with non-stem glioma cells. Depletion of KCTD2 using a KCTD2-specific short-hairpin RNA in U87MG glioma cells and primary Ink4a/Arf-deficient murine astrocytes markedly increased self-renewal activity in addition with an increased expression of stem cell markers, and mouse in vivo intracranial tumor growth. As an underlying mechanism for these KCTD2-mediated phenotypic changes, we demonstrated that KCTD2 interacts with c-Myc, which is a key stem cell factor, and causes c-Myc protein degradation by ubiquitination. As a result, KCTD2 depletion acquires GSC features and affects aerobic glycolysis via expression changes in glycolysis-associated genes through c-Myc protein regulation. Of clinical significance was our finding that patients having a profile of KCTD2 mRNA-low and c-Myc gene signature-high, but not KCTD2 mRNA-low and c-Myc mRNA-high, are strongly associated with poor prognosis. This study describes a novel regulatory mode of c-Myc protein in malignant gliomas and provides a potential framework for glioma therapy by targeting c-Myc function. PMID:28060381

Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

PubMed Central

Balz, Ellen; Herzog, Susann; Plantera, Laura; Vogelgesang, Silke; Seifert, Carolin; Bialke, Angela; Venugopal, Chitra; Singh, Sheila K.; Hoffmann, Wolfgang; Schroeder, Henry W. S.

2018-01-01

Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed. PMID:29535786

Effect of non-stationary accretion on spectral state transitions: An example of a persistent neutron star LMXB 4U1636–536

NASA Astrophysics Data System (ADS)

Zhang, Hui; Yu, Wen-Fei

2018-03-01

Observations of black hole and neutron star X-ray binaries show that the luminosity of the hard-to-soft state transition is usually higher than that of the soft-to-hard state transition, indicating additional parameters other than mass accretion rate are required to interpret spectral state transitions. It has been found in some individual black hole or neutron star soft X-ray transients that the luminosity corresponding to the hard-to-soft state transition is positively correlated with the peak luminosity of the following soft state. In this work, we report the discovery of the same correlation in the single persistent neutron star low mass X-ray binary (LMXB) 4U 1636–536 based on data from the All Sky Monitor (ASM) on board RXTE, the Gas Slit Camera (GSC) on board MAXI and the Burst Alert Telescope (BAT) on board Swift. We also found such a positive correlation holds in this persistent neutron star LMXB in a luminosity range spanning about a factor of four. Our results indicate that non-stationary accretion also plays an important role in driving X-ray spectral state transitions in persistent accreting systems with small accretion flares, which is much less dramatic compared with the bright outbursts seen in many Galactic LMXB transients.

Mitogenome metadata: current trends and proposed standards.

PubMed

Strohm, Jeff H T; Gwiazdowski, Rodger A; Hanner, Robert

2016-09-01

Mitogenome metadata are descriptive terms about the sequence, and its specimen description that allow both to be digitally discoverable and interoperable. Here, we review a sampling of mitogenome metadata published in the journal Mitochondrial DNA between 2005 and 2014. Specifically, we have focused on a subset of metadata fields that are available for GenBank records, and specified by the Genomics Standards Consortium (GSC) and other biodiversity metadata standards; and we assessed their presence across three main categories: collection, biological and taxonomic information. To do this we reviewed 146 mitogenome manuscripts, and their associated GenBank records, and scored them for 13 metadata fields. We also explored the potential for mitogenome misidentification using their sequence diversity, and taxonomic metadata on the Barcode of Life Datasystems (BOLD). For this, we focused on all Lepidoptera and Perciformes mitogenomes included in the review, along with additional mitogenome sequence data mined from Genbank. Overall, we found that none of 146 mitogenome projects provided all the metadata we looked for; and only 17 projects provided at least one category of metadata across the three main categories. Comparisons using mtDNA sequences from BOLD, suggest that some mitogenomes may be misidentified. Lastly, we appreciate the research potential of mitogenomes announced through this journal; and we conclude with a suggestion of 13 metadata fields, available on GenBank, that if provided in a mitogenomes's GenBank record, would increase their research value.

Downregulation of mitochondrial UQCRB inhibits cancer stem cell-like properties in glioblastoma.

PubMed

Jung, Narae; Kwon, Ho Jeong; Jung, Hye Jin

2018-01-01

Glioblastoma stem cell targeted therapies have become a powerful strategy for the treatment of this deadliest brain tumor. We demonstrate for the first time that downregulation of mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) inhibits the cancer stem cell-like properties in human glioblastoma cells. The synthetic small molecules targeting UQCRB significantly suppressed not only the self-renewal capacity such as growth and neurosphere formation, but also the metastatic potential such as migration and invasion of glioblastoma stem‑like cells (GSCs) derived from U87MG and U373MG at subtoxic concentrations. Notably, the UQCRB inhibitors repressed c‑Met-mediated downstream signal transduction and hypoxia‑inducible factor‑1α (HIF‑1α) activation, thereby reducing the expression levels of GSC markers including CD133, Nanog, Oct4 and Sox2 in the GSCs. Furthermore, the UQCRB inhibitors decreased mitochondrial ROS generation and mitochondrial membrane potential in the GSCs, indicating that they regulate the mitochondrial function in GSCs. Indeed, the knockdown of UQCRB gene by UQCRB siRNA significantly inhibited the cancer stem cell-like phenotypes as well as the expression of stemness markers by blocking mitochondrial ROS/HIF‑1α/c‑Met pathway in U87MG GSCs. These findings suggest that UQCRB and its inhibitors could be a new therapeutic target and lead compounds for eliminating cancer stem cells in glioblastoma.

Cdc2-like kinase 2 is a key regulator of the cell cycle via FOXO3a/p27 in glioblastoma.

PubMed

Park, Soon Young; Piao, Yuji; Thomas, Craig; Fuller, Gregory N; de Groot, John F

2016-05-03

Cdc2-like kinase 2 (CLK2) is known as a regulator of RNA splicing that ultimately controls multiple physiological processes. However, the function of CLK2 in glioblastoma progression has not been described. Reverse-phase protein array (RPPA) was performed to identify proteins differentially expressed in CLK2 knockdown cells compared to controls. The RPPA results indicated that CLK2 knockdown influenced the expression of survival-, proliferation-, and cell cycle-related proteins in GSCs. Thus, knockdown of CLK2 expression arrested the cell cycle at the G1 and S checkpoints in multiple GSC lines. Depletion of CLK2 regulated the dephosphorylation of AKT and decreased phosphorylation of Forkhead box O3a (FOXO3a), which not only translocated to the nucleus but also increased p27 expression. In two glioblastoma xenograft models, the survival duration of mice with CLK2-knockdown GSCs was significantly longer than mice with control tumors. Additionally, tumor volumes were significantly smaller in CLK2-knockdown mice than in controls. Knockdown of CLK2 expression reduced the phosphorylation of FOXO3a and decreased Ki-67 in vivo. Finally, high expression of CLK2 protien was significantly associated with worse patient survival. These findings suggest that CLK2 plays a critical role in controlling the cell cycle and survival of glioblastoma via FOXO3a/p27.

Cdc2-like kinase 2 is a key regulator of the cell cycle via FOXO3a/p27 in glioblastoma

PubMed Central

Thomas, Craig; Fuller, Gregory N.; de Groot, John F.

2016-01-01

Cdc2-like kinase 2 (CLK2) is known as a regulator of RNA splicing that ultimately controls multiple physiological processes. However, the function of CLK2 in glioblastoma progression has not been described. Reverse-phase protein array (RPPA) was performed to identify proteins differentially expressed in CLK2 knockdown cells compared to controls. The RPPA results indicated that CLK2 knockdown influenced the expression of survival-, proliferation-, and cell cycle-related proteins in GSCs. Thus, knockdown of CLK2 expression arrested the cell cycle at the G1 and S checkpoints in multiple GSC lines. Depletion of CLK2 regulated the dephosphorylation of AKT and decreased phosphorylation of Forkhead box O3a (FOXO3a), which not only translocated to the nucleus but also increased p27 expression. In two glioblastoma xenograft models, the survival duration of mice with CLK2-knockdown GSCs was significantly longer than mice with control tumors. Additionally, tumor volumes were significantly smaller in CLK2-knockdown mice than in controls. Knockdown of CLK2 expression reduced the phosphorylation of FOXO3a and decreased Ki-67 in vivo. Finally, high expression of CLK2 protien was significantly associated with worse patient survival. These findings suggest that CLK2 plays a critical role in controlling the cell cycle and survival of glioblastoma via FOXO3a/p27. PMID:27050366

Effects of High-Temperature-Pressure Polymerized Resin-Infiltrated Ceramic Networks on Oral Stem Cells

PubMed Central

Nassif, Ali; Berbar, Tsouria; Le Goff, Stéphane; Berdal, Ariane; Sadoun, Michael; Fournier, Benjamin P. J.

2016-01-01

Objectives The development of CAD—CAM techniques called for new materials suited to this technique and offering a safe and sustainable clinical implementation. The infiltration of resin in a ceramic network under high pressure and high temperature defines a new class of hybrid materials, namely polymer infiltrated ceramics network (PICN), for this purpose which requires to be evaluated biologically. We used oral stem cells (gingival and pulpal) as an in vitro experimental model. Methods Four biomaterials were grinded, immersed in a culture medium and deposed on stem cells from dental pulp (DPSC) and gingiva (GSC): Enamic (VITA®), Experimental Hybrid Material (EHM), EHM with initiator (EHMi) and polymerized Z100™ composite material (3M®). After 7 days of incubation; viability, apoptosis, proliferation, cytoskeleton, inflammatory response and morphology were evaluated in vitro. Results Proliferation was insignificantly delayed by all the tested materials. Significant cytotoxicity was observed in presence of resin based composites (MTT assay), however no detectable apoptosis and some dead cells were detected like in PICN materials. Cell morphology, major cytoskeleton and extracellular matrix components were not altered. An intimate contact appeared between the materials and cells. Clinical Significance The three new tested biomaterials did not exhibit adverse effects on oral stem cells in our experimental conditions and may be an interesting alternative to ceramics or composite based CAD—CAM blocks. PMID:27196425

Analysis of Dragon's Breath and Scattered Light Detector Anomalies on WFC3/UVIS

NASA Astrophysics Data System (ADS)

Fowler, Julia; Markwardt, Larissa; Bourque, Matthew; Anderson, Jay

2017-02-01

We summarize the examination of the light anomalies known as Dragon's Breath and Scattered Light for the UVIS channel of Wide Field Camera 3 (WFC3) of the Hubble Space Telescope (HST). We present three methods for WFC3 users to help avoid these effects during observation planning. We analyzed all of the full-frame wide and long pass filters with exposure times ≥ 300 seconds, comprising ∼13% of WFC3/UVIS on-orbit data (∼20% of all full-frame data, and ∼35% of all full-frame ≥300 second exposures.) We find that stars producing Dragon's Breath peak at specific orientations to the detector and V-band magnitudes. The bulk of these stars fall along the vertical and horizontal edges, within ∼490 pixels of the image frame. The corners of the detector show significantly fewer instances of Dragon's Breath and Scattered Light, though still a few occurrences. Furthermore, matching stars outside the field of the image to V-band magnitude data from the Hubble Guide Star Catalog II (GSC-II) shows that stars causing the anomaly consistently peak around a V-band magnitude of 11.9 or 14.6, whereas the general trend of objects lying outside the field instead peaks around a magnitude of 16.5 within our exposure time and filter selection.

Culture on 3D Chitosan-Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells.

PubMed

Wang, Kui; Kievit, Forrest M; Erickson, Ariane E; Silber, John R; Ellenbogen, Richard G; Zhang, Miqin

2016-12-01

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient-derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self-adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial-mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold-grown cells also display higher expression of genes that promote resistance to hypoxia-induced oxidative stress. In accord, scaffold-grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

PubMed Central

Giladi, Nis David; Ziv-Av, Amotz; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Ben-Asher, Hiba Waldman; deCarvalho, Ana; Mikkelsen, Tom; Poisson, Laila; Brodie, Chaya

2015-01-01

Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID:26267319

Orbital evolution and search for eccentricity and apsidal motion in the eclipsing HMXB 4U 1700-37

NASA Astrophysics Data System (ADS)

Islam, Nazma; Paul, Biswajit

2016-09-01

In the absence of detectable pulsations in the eclipsing high-mass X-ray binary 4U 1700-37, the orbital period decay is necessarily determined from the eclipse timing measurements. We have used the earlier reported mid-eclipse time measurements of 4U 1700-37 together with the new measurements from long-term light curves obtained with the all sky monitors RXTE-ASM, Swift-BAT and MAXI-GSC, as well as observations with RXTE-PCA, to measure the long-term orbital evolution of the binary. The orbital period decay rate of the system is estimated to be {dot{P}}/P = -(4.7 ± 1.9) × 10^{-7} yr-1, smaller compared to its previous estimates. We have also used the mid-eclipse times and the eclipse duration measurements obtained from 10-years-long X-ray light curve with Swift-BAT to separately put constraints on the eccentricity of the binary system and attempted to measure any apsidal motion. For an apsidal motion rate greater than 5 deg yr-1, the eccentricity is found to be less than 0.008, which limits our ability to determine the apsidal motion rate from the current data. We discuss the discrepancy of the current limit of eccentricity with the earlier reported values from radial velocity measurements of the companion star.

Nucleon scalar and tensor charges using lattice QCD simulations at the physical value of the pion mass

NASA Astrophysics Data System (ADS)

Alexandrou, C.; Constantinou, M.; Dimopoulos, P.; Frezzotti, R.; Hadjiyiannakou, K.; Jansen, K.; Kallidonis, C.; Kostrzewa, B.; Koutsou, G.; Mangin-Brinet, M.; Vaquero Avilès-Casco, A.; Wenger, U.

2017-06-01

We present results on the light, strange and charm nucleon scalar and tensor charges from lattice QCD, using simulations with Nf=2 flavors of twisted mass clover-improved fermions with a physical value of the pion mass. Both connected and disconnected contributions are included, enabling us to extract the isoscalar, strange and charm charges for the first time directly at the physical point. Furthermore, the renormalization is computed nonperturbatively for both isovector and isoscalar quantities. We investigate excited state effects by analyzing several sink-source time separations and by employing a set of methods to probe ground state dominance. Our final results for the scalar charges are gSu=5.20 (42 )(15 )(12 ), gSd=4.27 (26 )(15 )(12 ), gSs=0.33 (7 )(1 )(4 ), and gSc=0.062 (13 )(3 )(5 ) and for the tensor charges gTu=0.794 (16 )(2 )(13 ), gTd=-0.210 (10 )(2 )(13 ), gTs=0.00032 (24 )(0 ), and gTc=0.00062 (85 )(0 ) in the MS ¯ scheme at 2 GeV. The first error is statistical, the second is the systematic error due to the renormalization and the third the systematic arising from estimating the contamination due to the excited states, when our data are precise enough to probe the first excited state.

TrES-5: A MASSIVE JUPITER-SIZED PLANET TRANSITING A COOL G DWARF

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

Mandushev, Georgi; Dunham, Edward W.; Quinn, Samuel N.

2011-11-10

We report the discovery of TrES-5, a massive hot Jupiter that transits the star GSC 03949-00967 every 1.48 days. From spectroscopy of the star we estimate a stellar effective temperature of T{sub eff} = 5171 {+-} 36 K, and from high-precision B, R, and I photometry of the transit we constrain the ratio of the semimajor axis a and the stellar radius R{sub *} to be a/R{sub *} = 6.07 {+-} 0.14. We compare these values to model stellar isochrones to obtain a stellar mass of M{sub *} = 0.893 {+-} 0.024 M{sub Sun }. Based on this estimate andmore » the photometric time series, we constrain the stellar radius to be R{sub *} = 0.866 {+-} 0.013 R{sub Sun} and the planet radius to be R{sub p} = 1.209 {+-} 0.021 R{sub J}. We model our radial-velocity data assuming a circular orbit and find a planetary mass of 1.778 {+-} 0.063 M{sub J}. Our radial-velocity observations rule out line-bisector variations that would indicate a specious detection resulting from a blend of an eclipsing binary system. TrES-5 orbits one of the faintest stars with transiting planets found to date from the ground and demonstrates that precise photometry and followup spectroscopy are possible, albeit challenging, even for such faint stars.« less

A multilingual gold-standard corpus for biomedical concept recognition: the Mantra GSC

PubMed Central

Clematide, Simon; Akhondi, Saber A; van Mulligen, Erik M; Rebholz-Schuhmann, Dietrich

2015-01-01

Objective To create a multilingual gold-standard corpus for biomedical concept recognition. Materials and methods We selected text units from different parallel corpora (Medline abstract titles, drug labels, biomedical patent claims) in English, French, German, Spanish, and Dutch. Three annotators per language independently annotated the biomedical concepts, based on a subset of the Unified Medical Language System and covering a wide range of semantic groups. To reduce the annotation workload, automatically generated preannotations were provided. Individual annotations were automatically harmonized and then adjudicated, and cross-language consistency checks were carried out to arrive at the final annotations. Results The number of final annotations was 5530. Inter-annotator agreement scores indicate good agreement (median F-score 0.79), and are similar to those between individual annotators and the gold standard. The automatically generated harmonized annotation set for each language performed equally well as the best annotator for that language. Discussion The use of automatic preannotations, harmonized annotations, and parallel corpora helped to keep the manual annotation efforts manageable. The inter-annotator agreement scores provide a reference standard for gauging the performance of automatic annotation techniques. Conclusion To our knowledge, this is the first gold-standard corpus for biomedical concept recognition in languages other than English. Other distinguishing features are the wide variety of semantic groups that are being covered, and the diversity of text genres that were annotated. PMID:25948699

IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia.

PubMed

Kuo, Yung-Che; Au, Heng-Kien; Hsu, Jue-Liang; Wang, Hsiao-Feng; Lee, Chiung-Ju; Peng, Syue-Wei; Lai, Ssu-Chuan; Wu, Yu-Chih; Ho, Hong-Nerng; Huang, Yen-Hua

2018-02-13

Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R), and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation) and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A Genome-Wide Association Study Identifies a Novel Major Locus for Glycemic Control in Type 1 Diabetes, as Measured by Both A1C and Glucose

PubMed Central

Paterson, Andrew D.; Waggott, Daryl; Boright, Andrew P.; Hosseini, S. Mohsen; Shen, Enqing; Sylvestre, Marie-Pierre; Wong, Isidro; Bharaj, Bhupinder; Cleary, Patricia A.; Lachin, John M.; Below, Jennifer E.; Nicolae, Dan; Cox, Nancy J.; Canty, Angelo J.; Sun, Lei; Bull, Shelley B.

2010-01-01

OBJECTIVE Glycemia is a major risk factor for the development of long-term complications in type 1 diabetes; however, no specific genetic loci have been identified for glycemic control in individuals with type 1 diabetes. To identify such loci in type 1 diabetes, we analyzed longitudinal repeated measures of A1C from the Diabetes Control and Complications Trial. RESEARCH DESIGN AND METHODS We performed a genome-wide association study using the mean of quarterly A1C values measured over 6.5 years, separately in the conventional (n = 667) and intensive (n = 637) treatment groups of the DCCT. At loci of interest, linear mixed models were used to take advantage of all the repeated measures. We then assessed the association of these loci with capillary glucose and repeated measures of multiple complications of diabetes. RESULTS We identified a major locus for A1C levels in the conventional treatment group near SORCS1 (10q25.1, P = 7 × 10−10), which was also associated with mean glucose (P = 2 × 10−5). This was confirmed using A1C in the intensive treatment group (P = 0.01). Other loci achieved evidence close to genome-wide significance: 14q32.13 (GSC) and 9p22 (BNC2) in the combined treatment groups and 15q21.3 (WDR72) in the intensive group. Further, these loci gave evidence for association with diabetic complications, specifically SORCS1 with hypoglycemia and BNC2 with renal and retinal complications. We replicated the SORCS1 association in Genetics of Diabetes in Kidneys (GoKinD) study control subjects (P = 0.01) and the BNC2 association with A1C in nondiabetic individuals. CONCLUSIONS A major locus for A1C and glucose in individuals with diabetes is near SORCS1. This may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications. PMID:19875614

Transient stability enhancement of wind farms using power electronics and facts controllers

NASA Astrophysics Data System (ADS)

Mohammadpour, Hossein Ali

Nowadays, it is well-understood that the burning of fossil fuels in electric power station has a significant influence on the global climate due to greenhouse gases. In many countries, the use of cost-effective and reliable low-carbon electricity energy sources is becoming an important energy policy. Among different kinds of clean energy resources- such as solar power, hydro-power, ocean wave power and so on, wind power is the fastest-growing form of renewable energy at the present time. Moreover, adjustable speed generator wind turbines (ASGWT) has key advantages over the fixed-speed generator wind turbines (FSGWT) in terms of less mechanical stress, improved power quality, high system efficiency, and reduced acoustic noise. One important class of ASGWT is the doubly-fed induction generator (DFIG), which has gained a significant attention of the electric power industry due to their advantages over the other class of ASGWT, i.e. fully rated converter-based wind turbines. Because of increased integration of DFIG-based wind farms into electric power grids, it is necessary to transmit the generated power from wind farms to the existing grids via transmission networks without congestion. Series capacitive compensation of DFIG-based wind farm is an economical way to increase the power transfer capability of the transmission line connecting wind farm to the grid. For example, a study performed by ABB reveals that increasing the power transfer capability of an existing transmission line from 1300 MW to 2000 MW using series compensation is 90% less than the cost of building a new transmission line. However, a factor hindering the extensive use of series capacitive compensation is the potential risk of sub- synchronous resonance (SSR). The SSR is a condition where the wind farm exchanges energy with the electric network, to which it is connected, at one or more natural frequencies of the electric or mechanical part of the combined system, comprising the wind farm and the network, and the frequency of the exchanged energy is below the fundamental frequency of the system. This phenomenon may cause severe damage in the wind farm, if not prevented. Therefore, this dissertation deals with the SSR phenomena in a capacitive series compensated wind farm. A DFIG-based wind farm, which is connected to a series compensated transmission line, is considered as a case study. The small-signal stability analysis of the system is presented, and the eigenvalues of the system are obtained. Using both modal analysis and time-domain simulation, it is shown that the system is potentially unstable due to the SSR mode. Then, three different possibilities for the addition of SSR damping controller (SSRDC) are investigated. The SSRDC can be added to (1) gate-controlled series capacitor (GCSC), (2) thyristor-controlled series capacitor (TCSC), or (3) DFIG rotor-side converter (RSC) and grid-side converter (GSC) controllers. The first and second cases are related to the series flexible AC transmission systems (FACTS) family, and the third case uses the DFIG back-to-back converters to damp the SSR. The SSRDC is designed using residue-based analysis and root locus diagrams. Using residue-based analysis, the optimal input control signal (ICS) to the SSRDC is identified that can damp the SSR mode without destabilizing other modes, and using root-locus analysis, the required gain for the SSRDC is determined. Moreover, two methods are discussed in order to estimate the optimum input signal to the SSRDC, without measuring it directly. In this dissertation, MATLAB/Simulink is used as a tool for modeling and design of the SSRDC, and PSCAD/EMTDC is used to perform time-domain simulation in order to verify the design process.