Sample records for e2 modulate critical

  1. Review article: Critical Care Airway Management eLearning modules.

    PubMed

    Doshi, Deepak; McCarthy, Sally; Mowatt, Elizabeth; Cahill, Angela; Peirce, Bronwyn; Hawking, Geoff; Osborne, Ruth; Hibble, Belinda; Ebbs, Katharine

    2017-11-16

    The Australasian College for Emergency Medicine (ACEM) has recently launched the Critical Care Airway Management eLearning modules to support emergency medicine trainees in developing their airway management skills in the ED. A team of emergency physicians and trainees worked collaboratively to develop the eLearning resources ensuring extensive stakeholder consultation. A comprehensive resource manual was written to provide learners with knowledge that underpins the modules. ACEM provided project coordination as well as administrative and technical team support to the production. Although specifically developed with early ACEM trainees in mind, it is envisaged the resources will be useful for all emergency clinicians. The project was funded by the Australian Commonwealth Department of Health. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  2. Available, intuitive and free! Building e-learning modules using web 2.0 services.

    PubMed

    Tam, Chun Wah Michael; Eastwood, Anne

    2012-01-01

    E-learning is part of the mainstream in medical education and often provides the most efficient and effective means of engaging learners in a particular topic. However, translating design and content ideas into a useable product can be technically challenging, especially in the absence of information technology (IT) support. There is little published literature on the use of web 2.0 services to build e-learning activities. To describe the web 2.0 tools and solutions employed to build the GP Synergy evidence-based medicine and critical appraisal online course. We used and integrated a number of free web 2.0 services including: Prezi, a web-based presentation platform; YouTube, a video sharing service; Google Docs, a online document platform; Tiny.cc, a URL shortening service; and Wordpress, a blogging platform. The course consisting of five multimedia-rich, tutorial-like modules was built without IT specialist assistance or specialised software. The web 2.0 services used were free. The course can be accessed with a modern web browser. Modern web 2.0 services remove many of the technical barriers for creating and sharing content on the internet. When used synergistically, these services can be a flexible and low-cost platform for building e-learning activities. They were a pragmatic solution in our context.

  3. E2f1–3 Are Critical for Myeloid Development*

    PubMed Central

    Trikha, Prashant; Sharma, Nidhi; Opavsky, Rene; Reyes, Andres; Pena, Clarissa; Ostrowski, Michael C.; Roussel, Martine F.; Leone, Gustavo

    2011-01-01

    Hematopoietic development involves the coordinated activity of differentiation and cell cycle regulators. In current models of mammalian cell cycle control, E2f activators (E2f1, E2f2, and E2f3) are portrayed as the ultimate transcriptional effectors that commit cells to enter and progress through S phase. Using conditional gene knock-out strategies, we show that E2f1–3 are not required for the proliferation of early myeloid progenitors. Rather, these E2fs are critical for cell survival and proliferation at two distinct steps of myeloid development. First, E2f1–3 are required as transcriptional repressors for the survival of CD11b+ myeloid progenitors, and then they are required as activators for the proliferation of CD11b+ macrophages. In bone marrow macrophages, we show that E2f1–3 respond to CSF1-Myc mitogenic signals and serve to activate E2f target genes and promote their proliferation. Together, these findings expose dual functions for E2f1–3 at distinct stages of myeloid development in vivo, first as repressors in cell survival and then as activators in cell proliferation. In summary, this work places E2f1–3 in a specific signaling cascade that is critical for myeloid development in vivo. PMID:21115501

  4. eLearning to facilitate the education and implementation of the Chelsea Critical Care Physical Assessment: a novel measure of function in critical illness

    PubMed Central

    Corner, Evelyn J; Handy, Jonathan M; Brett, Stephen J

    2016-01-01

    Objective To evaluate the efficacy of eLearning in the widespread standardised teaching, distribution and implementation of the Chelsea Critical Care Physical Assessment (CPAx) tool—a validated tool to assess physical function in critically ill patients. Design Prospective educational study. An eLearning module was developed through a conceptual framework, using the four-stage technique for skills teaching to teach clinicians how to use the CPAx. Example and test video case studies of CPAx assessments were embedded within the module. The CPAx scores for the test case studies and demographic data were recorded in a secure area of the website. Data were analysed for inter-rater reliability using intraclass correlation coefficients (ICCs) to see if an eLearning educational package facilitated consistent use of the tool. A utility and content validity questionnaire was distributed after 1 year to eLearning module registrants (n=971). This was to evaluate uptake of the CPAx in clinical practice and content validity of the CPAx from the perspective of clinical users. Setting The module was distributed for use via professional forums (n=2) and direct contacts (n=95). Participants Critical care clinicians. Primary outcome measure ICC of the test case studies. Results Between July and October 2014, 421 candidates from 15 countries registered for the eLearning module. The ICC for case one was 0.996 (95% CI 0.990 to 0.999; n=207). The ICC for case two was 0.988 (0.996 to 1.000; n=184). The CPAx has a strong total scale content validity index (s-CVI) of 0.94 and is well used. Conclusions eLearning is a useful and reliable way of teaching psychomotor skills, such as the CPAx. The CPAx is a well-used measure with high content validity rated by clinicians. PMID:27067895

  5. eLearning to facilitate the education and implementation of the Chelsea Critical Care Physical Assessment: a novel measure of function in critical illness.

    PubMed

    Corner, Evelyn J; Handy, Jonathan M; Brett, Stephen J

    2016-04-11

    To evaluate the efficacy of eLearning in the widespread standardised teaching, distribution and implementation of the Chelsea Critical Care Physical Assessment (CPAx) tool-a validated tool to assess physical function in critically ill patients. Prospective educational study. An eLearning module was developed through a conceptual framework, using the four-stage technique for skills teaching to teach clinicians how to use the CPAx. Example and test video case studies of CPAx assessments were embedded within the module. The CPAx scores for the test case studies and demographic data were recorded in a secure area of the website. Data were analysed for inter-rater reliability using intraclass correlation coefficients (ICCs) to see if an eLearning educational package facilitated consistent use of the tool. A utility and content validity questionnaire was distributed after 1 year to eLearning module registrants (n=971). This was to evaluate uptake of the CPAx in clinical practice and content validity of the CPAx from the perspective of clinical users. The module was distributed for use via professional forums (n=2) and direct contacts (n=95). Critical care clinicians. ICC of the test case studies. Between July and October 2014, 421 candidates from 15 countries registered for the eLearning module. The ICC for case one was 0.996 (95% CI 0.990 to 0.999; n=207). The ICC for case two was 0.988 (0.996 to 1.000; n=184). The CPAx has a strong total scale content validity index (s-CVI) of 0.94 and is well used. eLearning is a useful and reliable way of teaching psychomotor skills, such as the CPAx. The CPAx is a well-used measure with high content validity rated by clinicians. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. 2D Materials for Optical Modulation: Challenges and Opportunities.

    PubMed

    Yu, Shaoliang; Wu, Xiaoqin; Wang, Yipei; Guo, Xin; Tong, Limin

    2017-04-01

    Owing to their atomic layer thickness, strong light-material interaction, high nonlinearity, broadband optical response, fast relaxation, controllable optoelectronic properties, and high compatibility with other photonic structures, 2D materials, including graphene, transition metal dichalcogenides and black phosphorus, have been attracting increasing attention for photonic applications. By tuning the carrier density via electrical or optical means that modifies their physical properties (e.g., Fermi level or nonlinear absorption), optical response of the 2D materials can be instantly changed, making them versatile nanostructures for optical modulation. Here, up-to-date 2D material-based optical modulation in three categories is reviewed: free-space, fiber-based, and on-chip configurations. By analysing cons and pros of different modulation approaches from material and mechanism aspects, the challenges faced by using these materials for device applications are presented. In addition, thermal effects (e.g., laser induced damage) in 2D materials, which are critical to practical applications, are also discussed. Finally, the outlook for future opportunities of these 2D materials for optical modulation is given. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Atypical E2f functions are critical for pancreas polyploidization

    PubMed Central

    Moreno, Eva; Toussaint, Mathilda J. M.; Tooten, Peter C. J.; van Essen, Saskia C.; van Liere, Elsbeth A.; Youssef, Sameh A.; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age. PMID:29329320

  8. Atypical E2f functions are critical for pancreas polyploidization.

    PubMed

    Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  9. Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes.

    PubMed

    Harizi, Hedi; Grosset, Christophe; Gualde, Norbert

    2003-06-01

    We have reported previously that PGE(2) inhibits dendritic cells (DC) functions. Because E prostanoid receptor (EPR) subtypes involved in this action are unknown, expression and functions of these receptors were examined in DC. Western blot and flow cytometry analyses showed that all EPRs were coexpressed in DC. In a dose-dependent manner, lipopolysaccharide (LPS) enhanced EP(2)R/EP(4)R but not EP(1)R/EP(3)R expressions. NS-398, a cyclooxygenase (COX)-2-selective inhibitor, suppressed LPS-enhanced EP(2)R/EP(4)R expression, suggesting that COX-2-issued prostaglandin E(2) (PGE(2)) modulates DC function through stimulation of specific EPR subtypes. Using selective agonists, we found that butaprost, an EP(2)R agonist, and PGE(1) alcohol, an EP(2)R and EP(2)R/EP(4)R agonist, inhibited major histocompatibility complex class II expression and enhanced interleukin-10 production from DC. However, no effect was observed with sulprostone and 17-phenyl-omega-trinor-PGE(2), selective agonists for EP(1)R and EP(1)R/EP(3)R, respectively. Treatment of DC with dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, mimics PGE(2)-induced, inhibitory effects. Taken together, our data demonstrate that EP(2)R/EP(4)R are efficient for mediating PGE(2)-induced modulation of DC functions.

  10. The Tomato U-Box Type E3 Ligase PUB13 Acts With Group III Ubiquitin E2 Enzymes to Modulate FLS2-Mediated Immune Signaling

    PubMed Central

    Zhou, Bangjun; Zeng, Lirong

    2018-01-01

    In Arabidopsis and rice, the ubiquitin ligase PUB13-mediated protein degradation plays a significant role in plant pattern-triggered immunity (PTI) and flowering time control. The Arabidopsis PUB13 has been shown to attenuate the pattern recognition receptor FLS2-mediated immune signaling by ubiquitinating FLS2 and consequently promoting its degradation by the 26S proteasome. Nevertheless, the cognate ubiquitin-conjugating enzymes (E2) with which PUB13 acts to modulate FLS2-mediated PTI are unknown. To address this question, we investigate here the tomato (Solanum lycopersicum) homolog of PUB13, SlPUB13 by utilizing the recently characterized complete set of tomato E2s. Of the 13 groups of tomato E2s, only members in group III are found to interact and act with SlPUB13. Knocking-down of the group III E2 genes enhances callose deposition and induction of the RbohB gene in the immunity-associated, early oxidative burst after flg22 treatment. The group III E2s are also found to work with SlPUB13 to ubiquitinate FLS2 in vitro and are required for PUB13-mediated degradation of FLS2 in vivo upon flg22 treatment, suggesting an essential role for group III E2s in the modulation of FLS2-mediated immune signaling by PUB13. Additionally, another immunity-associated E3, NtCMPG1 is shown to also work specifically with members of group III E2 in the in vitro ubiquitination assay, which implies the group III E2 enzymes may cooperate with many E3 ligases to regulate different aspects of PTI. Taken together, these data corroborate the notion that group III E2 enzymes play an important role in PTI and build a foundation for further functional and mechanistic characterization of tomato PUB13.

  11. Low-noise magnetometer based on inductance modulation in high-critical-temperature superconductor coil

    NASA Astrophysics Data System (ADS)

    Enpuku, Keiji; Matsuo, Masaaki; Yoshida, Yujiro; Yamashita, Shigeya; Sasayama, Teruyoshi; Yoshida, Takashi

    2018-06-01

    We developed a magnetometer based on inductance modulation of a coil made from a high-critical-temperature superconducting material. The coil inductance was modulated over time via a modulation current applied to a magnetic wire that was inserted into the coil. The magnetic field was then converted into a signal voltage using this time-dependent inductance. The relationship between magnetometer performance and the modulation current conditions was studied. Under appropriate conditions, the magnetometer had responsivity of 885 V/T. The magnetic field noise was 1.3 pT/Hz1/2 in the white noise region and 5.6 pT/Hz1/2 at f = 1 Hz.

  12. Adaptive eLearning modules for cytopathology education: A review and approach.

    PubMed

    Samulski, T Danielle; La, Teresa; Wu, Roseann I

    2016-11-01

    Clinical training imposes time and resource constraints on educators and learners, making it difficult to provide and absorb meaningful instruction. Additionally, innovative and personalized education has become an expectation of adult learners. Fortunately, the development of web-based educational tools provides a possible solution to these challenges. Within this review, we introduce the utility of adaptive eLearning platforms in pathology education. In addition to a review of the current literature, we provide the reader with a suggested approach for module creation, as well as a critical assessment of an available platform, based on our experience in creating adaptive eLearning modules for teaching basic concepts in gynecologic cytopathology. Diagn. Cytopathol. 2016;44:944-951. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Natural science modules with SETS approach to improve students’ critical thinking ability

    NASA Astrophysics Data System (ADS)

    Budi, A. P. S.; Sunarno, W.; Sugiyarto

    2018-05-01

    SETS (Science, Environment, Technology and Society) approach for learning is important to be developed for middle school, since it can improve students’ critical thinking ability. This research aimed to determine feasibility and the effectiveness of Natural Science Module with SETS approach to increase their critical thinking ability. The module development was done by invitation, exploration, explanation, concept fortifying, and assessment. Questionnaire and test performed including pretest and posttest with control group design were used as data collection technique in this research. Two classes were selected randomly as samples and consisted of 32 students in each group. Descriptive data analysis was used to analyze the module feasibility and t-test was used to analyze their critical thinking ability. The results showed that the feasibility of the module development has a very good results based on assessment of the experts, practitioners and peers. Based on the t-test results, there was significant difference between control class and experiment class (0.004), with n-gain score of control and the experiment class respectively 0.270 (low) and 0.470 (medium). It showed that the module was more effective than the textbook. It was able to improve students’ critical thinking ability and appropriate to be used in learning process.

  14. Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)*

    PubMed Central

    Atagi, Yuka; Liu, Chia-Chen; Painter, Meghan M.; Chen, Xiao-Fen; Verbeeck, Christophe; Zheng, Honghua; Li, Xia; Rademakers, Rosa; Kang, Silvia S.; Xu, Huaxi; Younkin, Steven; Das, Pritam; Fryer, John D.; Bu, Guojun

    2015-01-01

    Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Here, we report apolipoprotein E (apoE) as a novel ligand for TREM2. Using a biochemical assay, we demonstrated high-affinity binding of apoE to human TREM2. The functional significance of this binding was highlighted by increased phagocytosis of apoE-bound apoptotic N2a cells by primary microglia in a manner that depends on TREM2 expression. Moreover, when the AD-associated TREM2-R47H mutant was used in biochemical assays, apoE binding was vastly reduced. Our data demonstrate that apoE-TREM2 interaction in microglia plays critical roles in modulating phagocytosis of apoE-bound apoptotic neurons and establish a critical link between two proteins whose genes are strongly linked to the risk for AD. PMID:26374899

  15. Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.

    PubMed

    Melas, Philippe A; Qvist, Johanna S; Deidda, Matteo; Upreti, Chirag; Wei, Ya Bin; Sanna, Fabrizio; Fratta, Walter; Scherma, Maria; Fadda, Paola; Kandel, Denise B; Kandel, Eric R

    2018-03-13

    Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

    PubMed

    Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

    2006-07-01

    Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

  17. ROMPS critical design review. Volume 2: Robot module design documentation

    NASA Technical Reports Server (NTRS)

    Dobbs, M. E.

    1992-01-01

    The robot module design documentation for the Remote Operated Materials Processing in Space (ROMPS) experiment is compiled. This volume presents the following information: robot module modifications; Easylab commands definitions and flowcharts; Easylab program definitions and flowcharts; robot module fault conditions and structure charts; and C-DOC flow structure and cross references.

  18. Detection of eQTL modules mediated by activity levels of transcription factors.

    PubMed

    Sun, Wei; Yu, Tianwei; Li, Ker-Chau

    2007-09-01

    Studies of gene expression quantitative trait loci (eQTL) in different organisms have shown the existence of eQTL hot spots: each being a small segment of DNA sequence that harbors the eQTL of a large number of genes. Two questions of great interest about eQTL hot spots arise: (1) which gene within the hot spot is responsible for the linkages, i.e. which gene is the quantitative trait gene (QTG)? (2) How does a QTG affect the expression levels of many genes linked to it? Answers to the first question can be offered by available biological evidence or by statistical methods. The second question is harder to address. One simple situation is that the QTG encodes a transcription factor (TF), which regulates the expression of genes linked to it. However, previous results have shown that TFs are not overrepresented in the eQTL hot spots. In this article, we consider the scenario that the propagation of genetic perturbation from a QTG to other linked genes is mediated by the TF activity. We develop a procedure to detect the eQTL modules (eQTL hot spots together with linked genes) that are compatible with this scenario. We first detect 27 eQTL modules from a yeast eQTL data, and estimate TF activity profiles using the method of Yu and Li (2005). Then likelihood ratio tests (LRTs) are conducted to find 760 relationships supporting the scenario of TF activity mediation: (DNA polymorphism --> cis-linked gene --> TF activity --> downstream linked gene). They are organized into 4 eQTL modules: an amino acid synthesis module featuring a cis-linked gene LEU2 and the mediating TF Leu3; a pheromone response module featuring a cis-linked gene GPA1 and the mediating TF Ste12; an energy-source control module featuring two cis-linked genes, GSY2 and HAP1, and the mediating TF Hap1; a mitotic exit module featuring four cis-linked genes, AMN1, CSH1, DEM1 and TOS1, and the mediating TF complex Ace2/Swi5. Gene Ontology is utilized to reveal interesting functional groups of the downstream

  19. A-7E Software Module Guide.

    DTIC Science & Technology

    1981-12-08

    o 14 A& B:2.1 Function Driver Module.. ..... .... 14’ ’: B:2.2 Shared Services Module . . . o o . 0 -15 M’ 5:3 Software Decision Module...2.1.13 Weapon Release Functions... ........24 C:2.l.14 Ground Test Functions .. ........... 24 C:2.2 Shared Services Module Decomposition. ........24 C...Driver (FD) Module supported by a Shared Services (SS) Module. B:2.1 FUNCTION DRIVER MODULE The Function Driver Module consists of a set of individual

  20. Recommendations for the development of e-modules for the continuing professional development of European dentists.

    PubMed

    Kavadella, A; Kossioni, A E; Tsiklakis, K; Cowpe, J; Bullock, A; Barnes, E; Bailey, S; Thomas, H; Thomas, R; Karaharju-Suvanto, T; Suomalainen, K; Kersten, H; Povel, E; Giles, M; Walmsley, D; Soboleva, U; Liepa, A; Akota, I

    2013-05-01

    To provide evidence-based and peer-reviewed recommendations for the development of dental continuing professional development (CPD) learning e-modules. The present recommendations are consensus recommendations of the DentCPD project team and were informed by a literature research, consultations from e-learning and IT expert, discussions amongst the participants attending a special interest group during the 2012 ADEE meeting, and feedback from the evaluation procedures of the exemplar e-module (as described in a companion paper within this Supplement). The main focus of these recommendations is on the courses and modules organised and offered by dental schools. E-modules for dental CPD, as well as for other health professionals' continuing education, have been implemented and evaluated for a number of years. Research shows that the development of e-modules is a team process, undertaken by academics, subject experts, pedagogists, IT and web designers, learning technologists and librarians. The e-module must have clear learning objectives (outcomes), addressing the learners' individual needs, and must be visually attractive, relevant, interactive, promoting critical thinking and providing feedback. The text, graphics and animations must support the objectives and enable the learning process by creating an attractive, easy to navigate and interactive electronic environment. Technology is usually a concern for learners and tutors; therefore, it must be kept simple and interoperable within different systems and software. The pedagogical and technological proficiency of educators is of paramount importance, yet remains a challenge in many instances. The development of e-courses and modules for dental CPD is an endeavour undertaken by a group of professionals. It must be underpinned by sound pedagogical and e-learning principles and must incorporate elements for effective visual learning and visual design and a simple, consistent technology. © 2013 John Wiley & Sons A/S.

  1. Modulation of critical brain dynamics using closed-loop neurofeedback stimulation.

    PubMed

    Zhigalov, Alexander; Kaplan, Alexander; Palva, J Matias

    2016-08-01

    EEG long-range temporal correlations (LRTCs) are a significant for both human cognition and brain disorders, but beyond suppression by sensory disruption, there are little means for influencing them non-invasively. We hypothesized that LRTCs could be controlled by engaging intrinsic neuroregulation through closed-loop neurofeedback stimulation. We used a closed-loop-stimulation paradigm where supra-threshold α-waves trigger visual flash stimuli while the subject performs the standard eyes-closed resting-state task. As a "sham" control condition, we applied similar stimulus sequences without the neurofeedback. Over three sessions, a significant difference in the LRTCs of α-band oscillations (U=89, p<0.028, Wilcoxon rank sum test) and their scalp topography (T=-2.92, p<0.010, T-test) emerged between the neurofeedback and sham conditions so that the LRTCs were stronger during neurofeedback than sham. No changes (F=0.16, p>0.69, ANOVA test) in the scalp topography of α-band power were observed in either condition. This study provides proof-of-concept for that EEG LRTCs, and hence critical brain dynamics, can be modulated with closed-loop stimulation in an automatic, involuntary fashion. We suggest that this modulation is mediated by an excitation-inhibition balance change achieved by the closed-loop neuroregulation. Automatic LRTC modulation opens novel avenues for both examining the functional roles of brain criticality in healthy subjects and for developing novel therapeutic approaches for brain disorders associated with abnormal LRTCs. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Potential-induced degradation in photovoltaic modules: a critical review

    DOE PAGES

    Luo, Wei; Khoo, Yong Sheng; Hacke, Peter; ...

    2016-11-21

    Potential-induced degradation (PID) has received considerable attention in recent years due to its detrimental impact on photovoltaic (PV) module performance under field conditions. Both crystalline silicon (c-Si) and thin-film PV modules are susceptible to PID. While extensive studies have already been conducted in this area, the understanding of the PID phenomena is still incomplete and it remains a major problem in the PV industry. Herein, a critical review of the available literature is given to serve as a one-stop source for understanding the current status of PID research. This article also aims to provide an overview of future research pathsmore » to address PID-related issues. This paper consists of three parts. In the first part, the modelling of leakage current paths in the module package is discussed. The PID mechanisms in both c-Si and thin-film PV modules are also comprehensively reviewed. The second part summarizes various test methods to evaluate PV modules for PID. The last part focuses on studies related to PID in the omnipresent p-type c-Si PV modules. The dependence of temperature, humidity and voltage on the progression of PID is examined. Preventive measures against PID at the cell, module and system levels are illustrated. Moreover, PID recovery in standard p-type c-Si PV modules is also studied. Most of the findings from p-type c-Si PV modules are also applicable to other PV module technologies.« less

  3. NO2 inhalation promotes Alzheimer’s disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication

    NASA Astrophysics Data System (ADS)

    Yan, Wei; Yun, Yang; Ku, Tingting; Li, Guangke; Sang, Nan

    2016-03-01

    Air pollution has been reported to be associated with increased risks of cognitive impairment and neurodegenerative diseases. Because NO2 is a typical primary air pollutant and an important contributor to secondary aerosols, NO2-induced neuronal functional abnormalities have attracted greater attention, but the available experimental evidence, modulating mechanisms, and targeting medications remain ambiguous. In this study, we exposed C57BL/6J and APP/PS1 mice to dynamic NO2 inhalation and found for the first time that NO2 inhalation caused deterioration of spatial learning and memory, aggravated amyloid β42 (Aβ42) accumulation, and promoted pathological abnormalities and cognitive defects related to Alzheimer’s disease (AD). The microarray and bioinformation data showed that the cyclooxygenase-2 (COX-2)-mediated arachidonic acid (AA) metabolism of prostaglandin E2 (PGE2) played a key role in modulating this aggravation. Furthermore, increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented PGE2 production, neuroinflammation-associated Aβ42 accumulation, and neurodegeneration, indicating a therapeutic target for relieving cognitive impairment caused by NO2 exposure.

  4. Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation.

    PubMed

    Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C; Sessa, William C

    2015-08-18

    Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. Copyright © 2015, American Association for the Advancement of Science.

  5. Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

    PubMed Central

    Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C.; Sessa, William C.

    2016-01-01

    Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID:26286023

  6. Study of modulation property to incident laser by surface micro-defects on KH2PO4 crystal

    NASA Astrophysics Data System (ADS)

    Chen, Ming-Jun; Cheng, Jian; Li, Ming-Quan; Xiao, Yong

    2012-06-01

    KH2PO4 crystal is a crucial optical component of inertial confinement fusion. Modulation of an incident laser by surface micro-defects will induce the growth of surface damage, which largely restricts the enhancement of the laser induced damage threshold. The modulation of an incident laser by using different kinds of surface defects are simulated by employing the three-dimensional finite-difference time-domain method. The results indicate that after the modulation of surface defects, the light intensity distribution inside the crystal is badly distorted, with the light intensity enhanced symmetrically. The relations between modulation properties and defect geometries (e.g., width, morphology, and depth of defects) are quite different for different defects. The modulation action is most obvious when the width of surface defects reaches 1.064 μm. For defects with smooth morphology, such as spherical pits, the degree of modulation is the smallest and the light intensity distribution seems relatively uniform. The degree of modulation increases rapidly with the increase of the depth of surface defects and becomes stable when the depth reaches a critical value. The critical depth is 1.064 μm for cuboid pits and radial cracks, while for ellipsoidal pits the value depends on both the width and the length of the defects.

  7. Critical Analysis of an e-Learning and Interactive Teaching Module with Respect to the Interpretation of Emergency Computed Tomography of the Brain.

    PubMed

    Groth, Michael; Barthe, Käthe Greta; Riemer, Martin; Ernst, Marielle; Herrmann, Jochen; Fiehler, Jens; Buhk, Jan-Hendrik

    2018-04-01

    interactive teaching methods in radiology requires learning content-based considerations. · Groth M, Barthe KG, Riemer M et al. Critical Analysis of an e-Learning and Interactive Teaching Module with Respect to the Interpretation of Emergency Computed Tomography of the Brain. Fortschr Röntgenstr 2017; 190: 334 - 340. © Georg Thieme Verlag KG Stuttgart · New York.

  8. The β2-adrenoreceptor gene promoter polymorphisms may modulate β2-agonist- and glucocorticoid-induced IgE synthesis.

    PubMed

    Chalubinski, M; Grzegorczyk, J; Grzelak, A; Jarzebska, M; Kowalski, M L

    2014-01-01

    β2-adrenoreceptor (β2-AR) agonists and glucocorticoids (GCS) were shown to induce IgE synthesis in human PBMCs. Serum total IgE levels are associated with single nucleotide polymorphisms (SNPs) of the β2-AR gene. We aimed to assess the association of the effect of fenoterol (β2-AR agonist) on IL-4-driven and budesonide-induced IgE synthesis with genetic variants of β2-AR. The study included 25 individuals: 13 with allergic asthma and/or allergic rhinitis and 12 healthy volunteers. PBMCs were cultured with IL-4, fenoterol and/or budesonide, and IgE concentrations in supernatants were assessed. Five SNPs in positions: -47, -20, 46, 79 and 252 of β2-AR were determined by direct DNA sequencing. In -47 T/T and -20 T/T patients, incubation with fenoterol resulted in decreased IgE production, whereas in -47 C/T and -47 C/C as well as in -20 C/T and -20 C/C individuals, it was enhanced. In contrast to fenoterol, budesonide-induced IgE synthesis was significantly increased in -47 T/T and -20 T/T patients as compared to -47 C/T, -47 C/C, -20 C/T and -47 C/C individuals. Polymorphisms in positions 46, 79 and 252 were not associated with fenoterol- or budesonide-modulated IgE synthesis. No differences in the distribution of IgE synthesis was seen between atopic and non-atopic individuals carrying the same alleles. The differential effect of β2-agonists and GCS on IgE synthesis may be associated with genetic variants of promoter region of the β2-AR gene. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  9. Scale-4 Analysis of Pressurized Water Reactor Critical Configurations: Volume 2-Sequoyah Unit 2 Cycle 3

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

    Bowman, S.M.

    1995-01-01

    The requirements of ANSI/ANS 8.1 specify that calculational methods for away-from-reactor criticality safety analyses be validated against experimental measurements. If credit for the negative reactivity of the depleted (or spent) fuel isotopics is desired, it is necessary to benchmark computational methods against spent fuel critical configurations. This report summarizes a portion of the ongoing effort to benchmark away-from-reactor criticality analysis methods using critical configurations from commercial pressurized-water reactors. The analysis methodology selected for all the calculations reported herein is based on the codes and data provided in the SCALE-4 code system. The isotopic densities for the spent fuel assemblies inmore » the critical configurations were calculated using the SAS2H analytical sequence of the SCALE-4 system. The sources of data and the procedures for deriving SAS2H input parameters are described in detail. The SNIKR code module was used to extract the necessary isotopic densities from the SAS2H results and provide the data in the format required by the SCALE criticality analysis modules. The CSASN analytical sequence in SCALE-4 was used to perform resonance processing of the cross sections. The KENO V.a module of SCALE-4 was used to calculate the effective multiplication factor (k{sub eff}) of each case. The SCALE-4 27-group burnup library containing ENDF/B-IV (actinides) and ENDF/B-V (fission products) data was used for all the calculations. This volume of the report documents the SCALE system analysis of three reactor critical configurations for the Sequoyah Unit 2 Cycle 3. This unit and cycle were chosen because of the relevance in spent fuel benchmark applications: (1) the unit had a significantly long downtime of 2.7 years during the middle of cycle (MOC) 3, and (2) the core consisted entirely of burned fuel at the MOC restart. The first benchmark critical calculation was the MOC restart at hot, full-power (HFP) critical

  10. Post-translational regulation of P2X receptor channels: modulation by phospholipids

    PubMed Central

    Bernier, Louis-Philippe; Ase, Ariel R.; Séguéla, Philippe

    2013-01-01

    P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn) are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane. All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e., homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C (PLC)-linked metabotropic receptors and P2X receptor channels in dorsal root ganglion sensory neurons and microglia. PMID:24324400

  11. Ubiquitination independent of E1 and E2 enzymes by bacterial effectors

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

    Qiu, Jiazhang; Sheedlo, Michael J.; Yu, Kaiwen

    Signaling by ubiquitination regulates virtually every cellular process in eukaryotes. Covalent attachment of ubiquitin to a substrate is catalyzed by the E1, E2 and E3 three-enzyme cascade 1, which links the C terminus of ubiquitin via an isopeptide bond mostly to the ε-amino group of a lysine of the substrate. Given the essential roles of ubiquitination in the regulation of the immune system, it is not surprising that the ubiquitination network is a common target for diverse infectious agents 2. For example, many bacterial pathogens exploit ubiquitin signaling using virulence factors that function as E3 ligases, deubiquitinases 3 or asmore » enzymes that directly attack ubiquitin 4. The bacterial pathogen Legionella pneumophila utilizes approximately 300 effectors that modulate diverse host processes to create a niche permissive for its replication in phagocytes 5. Here we demonstrate that members of the SidE effector family (SidEs) of L. pneumophila ubiquitinate multiple Rab small GTPases associated with the endoplasmic reticulum (ER). Moreover, we show that these proteins are capable of catalyzing ubiquitination without the need for the E1 and E2 enzymes. The E1/E2-independent ubiquitination catalyzed by these enzymes requires NAD but not ATP and Mg2+. A putative mono ADP-ribosyltransferase (mART) motif critical for the ubiquitination activity is also essential for the role of SidEs in intracellular bacterial replication in a protozoan host. These results establish that ubiquitination can be catalyzed by a single enzyme.« less

  12. Brd4 modulates the innate immune response through Mnk2-eIF4E pathway-dependent translational control of IκBα.

    PubMed

    Bao, Yan; Wu, Xuewei; Chen, Jinjing; Hu, Xiangming; Zeng, Fuxing; Cheng, Jianjun; Jin, Hong; Lin, Xin; Chen, Lin-Feng

    2017-05-16

    Bromodomain-containing factor Brd4 has emerged as an important transcriptional regulator of NF-κB-dependent inflammatory gene expression. However, the in vivo physiological function of Brd4 in the inflammatory response remains poorly defined. We now demonstrate that mice deficient for Brd4 in myeloid-lineage cells are resistant to LPS-induced sepsis but are more susceptible to bacterial infection. Gene-expression microarray analysis of bone marrow-derived macrophages (BMDMs) reveals that deletion of Brd4 decreases the expression of a significant amount of LPS-induced inflammatory genes while reversing the expression of a small subset of LPS-suppressed genes, including MAP kinase-interacting serine/threonine-protein kinase 2 ( Mknk2 ). Brd4 -deficient BMDMs display enhanced Mnk2 expression and the corresponding eukaryotic translation initiation factor 4E (eIF4E) activation after LPS stimulation, leading to an increased translation of IκBα mRNA in polysomes. The enhanced newly synthesized IκBα reduced the binding of NF-κB to the promoters of inflammatory genes, resulting in reduced inflammatory gene expression and cytokine production. By modulating the translation of IκBα via the Mnk2-eIF4E pathway, Brd4 provides an additional layer of control for NF-κB-dependent inflammatory gene expression and inflammatory response.

  13. Active Site Gate Dynamics Modulate the Catalytic Activity of the Ubiquitination Enzyme E2-25K.

    PubMed

    Rout, Manoj K; Lee, Brian L; Lin, Aiyang; Xiao, Wei; Spyracopoulos, Leo

    2018-05-03

    The ubiquitin proteasome system (UPS) signals for degradation of proteins through attachment of K48-linked polyubiquitin chains, or alterations in protein-protein recognition through attachment of K63-linked chains. Target proteins are ubiquitinated in three sequential chemical steps by a three-component enzyme system. Ubiquitination, or E2 enzymes, catalyze the central step by facilitating reaction of a target protein lysine with the C-terminus of Ub that is attached to the active site cysteine of the E2 through a thioester bond. E2 reactivity is modulated by dynamics of an active site gate, whose central residue packs against the active site cysteine in a closed conformation. Interestingly, for the E2 Ubc13, which specifically catalyzes K63-linked ubiquitination, the central gate residue adopts an open conformation. We set out to determine if active site gate dynamics play a role in catalysis for E2-25K, which adopts the canonical, closed gate conformation, and which selectively synthesizes K48-linked ubiquitin chains. Gate dynamics were characterized using mutagenesis of key residues, combined with enzyme kinetics measurements, and main chain NMR relaxation. The experimental data were interpreted with all atom MD simulations. The data indicate that active site gate opening and closing rates for E2-25K are precisely balanced.

  14. Development of an e-Learning Research Module Using Multimedia Instruction Approach.

    PubMed

    Kowitlawakul, Yanika; Chan, Moon Fai; Tan, Sharon Swee Lin; Soong, Alan Swee Kit; Chan, Sally Wai Chi

    2017-03-01

    Students nowadays feel more comfortable with new technologies, which increase their motivation and, as a result, improve their academic performance. In the last two decades, the use of information communication technology has been increasing in many disciplines in higher education. Online learning or e-learning has been used and integrated into the curriculum around the world. A team of nursing faculty and educational technology specialists have developed an e-learning research module and integrate it into the nursing curriculum. The aim was to assist master of nursing and postgraduate nursing students in developing their research knowledge before and throughout their enrollment in the research course. This e-learning module includes interactive multimedia such as audiovisual presentation, graphical theme, animation, case-based learning, and pretest and posttest for each topic area. The module focuses on three main topic areas: (1) basic research principles (for review), (2) quantitative method, and (3) qualitative method. The e-learning module is an innovative use of the information and communication technology to enhance student engagement and learning outcomes in a local context. This article discusses the development journey, piloting process, including the variety of evaluation perspectives, and the ways in which the results influenced the e-learning resource before its wider distribution.

  15. Stromal Cells Positively and Negatively Modulate the Growth of Cancer Cells: Stimulation via the PGE2-TNFα-IL-6 Pathway and Inhibition via Secreted GAPDH-E-Cadherin Interaction

    PubMed Central

    Kawada, Manabu; Inoue, Hiroyuki; Ohba, Shun-ichi; Yoshida, Junjiro; Masuda, Tohru; Yamasaki, Manabu; Usami, Ihomi; Sakamoto, Shuichi; Abe, Hikaru; Watanabe, Takumi; Yamori, Takao; Shibasaki, Masakatsu; Nomoto, Akio

    2015-01-01

    Fibroblast-like stromal cells modulate cancer cells through secreted factors and adhesion, but those factors are not fully understood. Here, we have identified critical stromal factors that modulate cancer growth positively and negatively. Using a cell co-culture system, we found that gastric stromal cells secreted IL-6 as a growth and survival factor for gastric cancer cells. Moreover, gastric cancer cells secreted PGE2 and TNFα that stimulated IL-6 secretion by the stromal cells. Furthermore, we found that stromal cells secreted glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Extracellular GAPDH, or its N-terminal domain, inhibited gastric cancer cell growth, a finding confirmed in other cell systems. GAPDH bound to E-cadherin and downregulated the mTOR-p70S6 kinase pathway. These results demonstrate that stromal cells could regulate cancer cell growth through the balance of these secreted factors. We propose that negative regulation of cancer growth using GAPDH could be a new anti-cancer strategy. PMID:25785838

  16. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

    PubMed

    Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

    2014-12-01

    Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Critical field-exponents for secure message-passing in modular networks

    NASA Astrophysics Data System (ADS)

    Shekhtman, Louis M.; Danziger, Michael M.; Bonamassa, Ivan; Buldyrev, Sergey V.; Caldarelli, Guido; Zlatić, Vinko; Havlin, Shlomo

    2018-05-01

    We study secure message-passing in the presence of multiple adversaries in modular networks. We assume a dominant fraction of nodes in each module have the same vulnerability, i.e., the same entity spying on them. We find both analytically and via simulations that the links between the modules (interlinks) have effects analogous to a magnetic field in a spin-system in that for any amount of interlinks the system no longer undergoes a phase transition. We then define the exponents δ, which relates the order parameter (the size of the giant secure component) at the critical point to the field strength (average number of interlinks per node), and γ, which describes the susceptibility near criticality. These are found to be δ = 2 and γ = 1 (with the scaling of the order parameter near the critical point given by β = 1). When two or more vulnerabilities are equally present in a module we find δ = 1 and γ = 0 (with β ≥ 2). Apart from defining a previously unidentified universality class, these exponents show that increasing connections between modules is more beneficial for security than increasing connections within modules. We also measure the correlation critical exponent ν, and the upper critical dimension d c , finding that ν {d}c=3 as for ordinary percolation, suggesting that for secure message-passing d c = 6. These results provide an interesting analogy between secure message-passing in modular networks and the physics of magnetic spin-systems.

  18. Hepatitis C Virus Strain-Dependent Usage of Apolipoprotein E Modulates Assembly Efficiency and Specific Infectivity of Secreted Virions.

    PubMed

    Weller, Romy; Hueging, Kathrin; Brown, Richard J P; Todt, Daniel; Joecks, Sebastian; Vondran, Florian W R; Pietschmann, Thomas

    2017-09-15

    Hepatitis C virus (HCV) is extraordinarily diverse and uses entry factors in a strain-specific manner. Virus particles associate with lipoproteins, and apolipoprotein E (ApoE) is critical for HCV assembly and infectivity. However, whether ApoE dependency is common to all HCV genotypes remains unknown. Therefore, we compared the roles of ApoE utilizing 10 virus strains from genotypes 1 through 7. ApoA and ApoC also support HCV assembly, so they may contribute to virus production in a strain-dependent fashion. Transcriptome sequencing (RNA-seq) revealed abundant coexpression of ApoE, ApoB, ApoA1, ApoA2, ApoC1, ApoC2, and ApoC3 in primary hepatocytes and in Huh-7.5 cells. Virus production was examined in Huh-7.5 cells with and without ApoE expression and in 293T cells where individual apolipoproteins (ApoE1, -E2, -E3, -A1, -A2, -C1, and -C3) were provided in trans All strains were strictly ApoE dependent. However, ApoE involvement in virus production was strain and cell type specific, because some HCV strains poorly produced infectious virus in ApoE-expressing 293T cells and because ApoE knockout differentially affected virus production of HCV strains in Huh-7.5 cells. ApoE allelic isoforms (ApoE2, -E3, and -E4) complemented virus production of HCV strains to comparable degrees. All tested strains assembled infectious progeny with ApoE in preference to other exchangeable apolipoproteins (ApoA1, -A2, -C1, and -C3). The specific infectivity of HCV particles was similar for 293T- and Huh-7.5-derived particles for most strains; however, it differed by more than 100-fold in some viruses. Collectively, this study reveals strain-dependent and host cell-dependent use of ApoE during HCV assembly. These differences relate to the efficacy of virus production and also to the properties of released virus particles and therefore govern viral fitness at the level of assembly and cell entry. IMPORTANCE Chronic HCV infections are a major cause of liver disease. HCV is highly variable

  19. Large Work Function Modulation of Monolayer MoS2 by Ambient Gases.

    PubMed

    Lee, Si Young; Kim, Un Jeong; Chung, JaeGwan; Nam, Honggi; Jeong, Hye Yun; Han, Gang Hee; Kim, Hyun; Oh, Hye Min; Lee, Hyangsook; Kim, Hyochul; Roh, Young-Geun; Kim, Jineun; Hwang, Sung Woo; Park, Yeonsang; Lee, Young Hee

    2016-06-28

    Although two-dimensional monolayer transition-metal dichalcogenides reveal numerous unique features that are inaccessible in bulk materials, their intrinsic properties are often obscured by environmental effects. Among them, work function, which is the energy required to extract an electron from a material to vacuum, is one critical parameter in electronic/optoelectronic devices. Here, we report a large work function modulation in MoS2 via ambient gases. The work function was measured by an in situ Kelvin probe technique and further confirmed by ultraviolet photoemission spectroscopy and theoretical calculations. A measured work function of 4.04 eV in vacuum was converted to 4.47 eV with O2 exposure, which is comparable with a large variation in graphene. The homojunction diode by partially passivating a transistor reveals an ideal junction with an ideality factor of almost one and perfect electrical reversibility. The estimated depletion width obtained from photocurrent mapping was ∼200 nm, which is much narrower than bulk semiconductors.

  20. The need analysis of chemistry module based on REACT (relating, experiencing, applying, cooperating and transferring) to improve critical thinking ability

    NASA Astrophysics Data System (ADS)

    Tyffani, D. M.; Utomo, S. B.; Rahardjo, S. B.

    2018-05-01

    This research was aimed to find out how students’ need of chemistry module based REACT (Relating, Experiencing, Applying, Cooperating and Transferring) to improve students’ critical thinking ability. The subjects of this research was the studentsof XI grade in three school in even semester of academic year 2016-2017 that contained of 48 students of Senior High School 2 Bandar Lampung, 38 students of Senior High School 3 Bandar Lampung and 46 students of Senior High School 12 Bandar Lampung. The data was gathering used non-test method by using open questionnaire with 13 questions. The results showed that 84,84% of students stated that the development of chemistry module based REACT on colloid material is needed. The analysis of hand’s book was used aspects of critical thinking proposed by Facione (2011) are interpretation, analysis, evaluation, conclusion, and explanation. Based on the result of the analysis of hand’s book at Senior High School 12 Bandar Lampung for critical thinking in colloid material that indicate 50% indicator is appropriate, while for indicator of inference and explanation only 16,67% appropriate, then for indicator analysis and evaluation doesn’t have conformity. Based on the results of the analysis shows that the hand’s book used have not empowered critical thinking ability with maximum. The development of chemistry module on colloid material is needed to overcome the problem of hand’s book that hasn’t maximized critical thinking ability, then the development of module oriented to REACT learning model (Relating, Experiencing, Applying, Cooperating, and Transferring).

  1. 20-Hydroxyecdysone (20E) Primary Response Gene E93 Modulates 20E Signaling to Promote Bombyx Larval-Pupal Metamorphosis*

    PubMed Central

    Liu, Xi; Dai, Fangyin; Guo, Enen; Li, Kang; Ma, Li; Tian, Ling; Cao, Yang; Zhang, Guozheng; Palli, Subba R.; Li, Sheng

    2015-01-01

    As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis. PMID:26378227

  2. 20-Hydroxyecdysone (20E) Primary Response Gene E93 Modulates 20E Signaling to Promote Bombyx Larval-Pupal Metamorphosis.

    PubMed

    Liu, Xi; Dai, Fangyin; Guo, Enen; Li, Kang; Ma, Li; Tian, Ling; Cao, Yang; Zhang, Guozheng; Palli, Subba R; Li, Sheng

    2015-11-06

    As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Impact of Interactive e-Learning Modules on Appropriateness of Imaging Referrals: A Multicenter, Randomized, Crossover Study.

    PubMed

    Velan, Gary M; Goergen, Stacy K; Grimm, Jane; Shulruf, Boaz

    2015-11-01

    Health care expenditure on diagnostic imaging investigations is increasing, and many tests are ordered inappropriately. Validated clinical decision rules (CDRs) for certain conditions are available to aid in assessing the need for imaging. However, awareness and utilization of CDRs are lacking. This study compared the efficacy and perceived impact of interactive e-learning modules versus static versions of CDRs, for learning about appropriate imaging referrals. A multicenter, randomized, crossover trial was performed; participants were volunteer medical students and recent graduates. In week 1, group 1 received an e-learning module on appropriate imaging referrals for pulmonary embolism; group 2 received PDF versions of relevant CDRs, and an online quiz with feedback. In week 2, the groups crossed over, focusing on imaging referrals for cervical spine trauma in adults. Online assessments were administered to both groups at the end of each week, and participants completed an online questionnaire at the end of the trial. Group 1 (e-learning module) performed significantly better on the pulmonary embolism knowledge assessment. After the crossover, participants in group 2 (e-learning module) were significantly more likely to improve their scores in the assessment of cervical spine trauma knowledge. Both groups gave positive evaluations of the e-learning modules. Interactive e-learning was significantly more effective for learning in this cohort, compared with static CDRs. We believe that the authentic clinical scenarios, feedback, and integration provided by the e-learning modules contributed to their impact. This study has implications for implementation of e-learning tools to facilitate appropriate referrals for imaging investigations in clinical practice. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  4. Web-based resources for critical care education.

    PubMed

    Kleinpell, Ruth; Ely, E Wesley; Williams, Ged; Liolios, Antonios; Ward, Nicholas; Tisherman, Samuel A

    2011-03-01

    To identify, catalog, and critically evaluate Web-based resources for critical care education. A multilevel search strategy was utilized. Literature searches were conducted (from 1996 to September 30, 2010) using OVID-MEDLINE, PubMed, and the Cumulative Index to Nursing and Allied Health Literature with the terms "Web-based learning," "computer-assisted instruction," "e-learning," "critical care," "tutorials," "continuing education," "virtual learning," and "Web-based education." The Web sites of relevant critical care organizations (American College of Chest Physicians, American Society of Anesthesiologists, American Thoracic Society, European Society of Intensive Care Medicine, Society of Critical Care Medicine, World Federation of Societies of Intensive and Critical Care Medicine, American Association of Critical Care Nurses, and World Federation of Critical Care Nurses) were reviewed for the availability of e-learning resources. Finally, Internet searches and e-mail queries to critical care medicine fellowship program directors and members of national and international acute/critical care listserves were conducted to 1) identify the use of and 2) review and critique Web-based resources for critical care education. To ensure credibility of Web site information, Web sites were reviewed by three independent reviewers on the basis of the criteria of authority, objectivity, authenticity, accuracy, timeliness, relevance, and efficiency in conjunction with suggested formats for evaluating Web sites in the medical literature. Literature searches using OVID-MEDLINE, PubMed, and the Cumulative Index to Nursing and Allied Health Literature resulted in >250 citations. Those pertinent to critical care provide examples of the integration of e-learning techniques, the development of specific resources, reports of the use of types of e-learning, including interactive tutorials, case studies, and simulation, and reports of student or learner satisfaction, among other general

  5. MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in endometrial carcinoma

    PubMed Central

    Lu, Zheng; Nian, Zhou; Jingjing, Zhang; Tao, Luo; Quan, Li

    2017-01-01

    Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro. Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC. PMID:29371986

  6. The Student Experience of a Collaborative E-Learning University Module

    ERIC Educational Resources Information Center

    Biasutti, Michele

    2011-01-01

    The aim of this paper is to present a picture of student experience of a collaborative e-learning module in an asynchronous e-learning environment. A distance learning module on music education worth five credit points for a bachelor online degree for primary school educating teachers was assessed using a self-evaluation questionnaire that…

  7. p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

    PubMed Central

    Deng, Wen; Zhou, Yuan; Tiwari, Agnes FY; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie LM; Guan, Xin-Yuan; Tsao, Sai Wah

    2015-01-01

    Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. PMID:25131797

  8. Impact of a multimedia e-learning module on colon cancer literacy: a community-based pilot study.

    PubMed

    Holubar, Stefan D; Hassinger, J Peyton; Dozois, Eric J; Wolff, Bruce G; Kehoe, Michael; Cima, Robert R

    2009-10-01

    We aimed to determine if an e-learning module could improve colon cancer literacy in a community-based cohort, while obtaining variability estimates for subsequent study. A convenience sample of subjects attending a health-education fair was surveyed to determine colon cancer literacy before-and-after viewing a colon cancer e-learning module. The difference in cancer literacy scores was assessed for significance using univariate analysis. Twenty-two eligible subjects completed the survey: mean age 77.2+/-7.5 y, 55% women; 67% had at least some graduate-level education. Baseline colon cancer literacy was 72.6% +/- 11.6%; after the e-learning module, the mean colon cancer literacy score was 75.5% +/- 12.2%, representing a 3% improvement (P=0.33). After excluding a single problematic item identified by item analysis, the adjusted improvement was 7% (P=0.04). Invasiveness, malignant, and metastatic remained poorly understood concepts, while a large improvement (45%) was seen regarding the role of routine lymphadenectomy. Subject satisfaction with the module was universally (100%) high or very high. Use of an e-learning module is associated with high patient satisfaction, and has potential to improve colon cancer literacy in laypersons. Randomized study is warranted to determine the incremental impact of this and other multimedia educational interventions.

  9. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes.

    PubMed

    Overmiller, Andrew M; Pierluissi, Jennifer A; Wermuth, Peter J; Sauma, Sami; Martinez-Outschoorn, Ubaldo; Tuluc, Madalina; Luginbuhl, Adam; Curry, Joseph; Harshyne, Larry A; Wahl, James K; South, Andrew P; Mahoney, Mỹ G

    2017-08-01

    Extracellular vesicles (EVs) are nanoscale membrane-derived vesicles that serve as intercellular messengers carrying lipids, proteins, and genetic material. Substantial evidence has shown that cancer-derived EVs, secreted by tumor cells into the blood and other bodily fluids, play a critical role in modulating the tumor microenvironment and affecting the pathogenesis of cancer. Here we demonstrate for the first time that squamous cell carcinoma (SCC) EVs were enriched with the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in malignancies. Overexpression of Dsg2 increased EV release and mitogenic content including epidermal growth factor receptor and c-Src. Inhibiting ectodomain shedding of Dsg2 with the matrix metalloproteinase inhibitor GM6001 resulted in accumulation of full-length Dsg2 in EVs and reduced EV release. When cocultured with Dsg2/green fluorescence protein-expressing SCC cells, green fluorescence protein signal was detected by fluorescence-activated cell sorting analysis in the CD90 + fibroblasts. Furthermore, SCC EVs activated Erk1/2 and Akt signaling and enhanced fibroblast cell proliferation. In vivo, Dsg2 was highly up-regulated in the head and neck SCCs, and EVs isolated from sera of patients with SCC were enriched in Dsg2 C-terminal fragment and epidermal growth factor receptor. This study defines a mechanism by which Dsg2 expression in cancer cells can modulate the tumor microenvironment, a step critical for tumor progression.-Overmiller, A. M., Pierluissi, J. A., Wermuth, P. J., Sauma, S., Martinez-Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L. A., Wahl, J. K. III, South, A. P., Mahoney, M. G. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes. © FASEB.

  10. Product Module Rig Test

    NASA Technical Reports Server (NTRS)

    Holdeman, James D. (Technical Monitor); Chiappetta, Louis, Jr.; Hautman, Donald J.; Ols, John T.; Padget, Frederick C., IV; Peschke, William O. T.; Shirley, John A.; Siskind, Kenneth S.

    2004-01-01

    The low emissions potential of a Rich-Quench-Lean (RQL) combustor for use in the High Speed Civil Transport (HSCT) application was evaluated as part of Work Breakdown Structure (WBS) 1.0.2.7 of the NASA Critical Propulsion Components (CPC) Program under Contract NAS3-27235. Combustion testing was conducted in cell 1E of the Jet Burner Test Stand at United Technologies Research Center. Specifically, a Rich-Quench-Lean combustor, utilizing reduced scale quench technology implemented in a quench vane concept in a product-like configuration (Product Module Rig), demonstrated the capability of achieving an emissions index of nitrogen oxides (NOx EI) of 8.5 gm/Kg fuel at the supersonic flight condition (relative to the program goal of 5 gm/Kg fuel). Developmental parametric testing of various quench vane configurations in the more fundamental flametube, Single Module Rig Configuration, demonstrated NOx EI as low as 5.2. All configurations in both the Product Module Rig configuration and the Single Module Rig configuration demonstrated exceptional efficiencies, greater than 99.95 percent, relative to the program goal of 99.9 percent efficiency at supersonic cruise conditions. Sensitivity of emissions to quench orifice design parameters were determined during the parametric quench vane test series in support of the design of the Product Module Rig configuration. For the rectangular quench orifices investigated, an aspect ratio (length/width) of approximately 2 was found to be near optimum. An optimum for orifice spacing was found to exist at approximately 0.167 inches, resulting in 24 orifices per side of a quench vane, for the 0.435 inch quench zone channel height investigated in the Single Module Rig. Smaller quench zone channel heights appeared to be beneficial in reducing emissions. Measurements were also obtained in the Single Module Rig configuration on the sensitivity of emissions to the critical combustor parameters of fuel/air ratio, pressure drop, and residence

  11. Developing Critically Thoughtful e-Learning Communities of Practice

    ERIC Educational Resources Information Center

    Balcaen, Philip L.; Hirtz, Janine R.

    2007-01-01

    In this paper, we consider an approach to developing critically thoughtful e-Learning communities of practice--where participants are deliberate about the use of specific intellectual tools supporting critical thinking. We address Garrison & Anderson's (2003) argument that such critical thinking should play a central role within the ecology of…

  12. E-type cyclins modulate telomere integrity in mammalian male meiosis.

    PubMed

    Manterola, Marcia; Sicinski, Piotr; Wolgemuth, Debra J

    2016-06-01

    We have shown that E-type cyclins are key regulators of mammalian male meiosis. Depletion of cyclin E2 reduced fertility in male mice due to meiotic defects, involving abnormal pairing and synapsis, unrepaired DNA, and loss of telomere structure. These defects were exacerbated by additional loss of cyclin E1, and complete absence of both E-type cyclins produces a meiotic catastrophe. Here, we investigated the involvement of E-type cyclins in maintaining telomere integrity in male meiosis. Spermatocytes lacking cyclin E2 and one E1 allele (E1+/-E2-/-) displayed a high rate of telomere abnormalities but can progress to pachytene and diplotene stages. We show that their telomeres exhibited an aberrant DNA damage repair response during pachynema and that the shelterin complex proteins TRF2 and RAP2 were significantly decreased in the proximal telomeres. Moreover, the insufficient level of these proteins correlated with an increase of γ-H2AX foci in the affected telomeres and resulted in telomere associations involving TRF1 and telomere detachment in later prophase-I stages. These results suggest that E-type cyclins are key modulators of telomere integrity during meiosis by, at least in part, maintaining the balance of shelterin complex proteins, and uncover a novel role of E-type cyclins in regulating chromosome structure during male meiosis.

  13. The relationship between amplitude modulation, coherent structure and critical layers in wall turbulence

    NASA Astrophysics Data System (ADS)

    McKeon, Beverley

    2015-11-01

    The importance of critical layers in determining aspects of the structure of wall turbulence is discussed. We have shown (Jacobi & McKeon, 2013) that the amplitude modulation coefficient investigated most recently by Hutchins & Marusic (2007) and co-authors, which describes the correlation between large scales above a (spatial) wavelength filter with the envelope of small scales below the filter, is dominated by very large scale motion (VLSM) at a single wavelength. The resolvent analysis of McKeon & Sharma (2010) gives a suitable model for the three-dimensional, three-component form of the VLSM and energetic structure at other wavelengths. This model is used to identify the three-dimensional spatial variation of instantaneous critical layers in the presence of a mean velocity profile and to relate this to earlier observations of coherent structure in unperturbed flows (both experimental and via the resolvent model, Sharma & McKeon, 2013); to the phase relationships between scales identified by Chung & McKeon (2010, 2014); and to the structure of wall turbulence that has been modified by the addition of single synthetic scales, e.g. Jacobi & McKeon (2011), Duvvuri & McKeon (2015). The support of AFOSR under grant number FA 9550-12-1-0469 is gratefully acknowledged.

  14. Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

    ERIC Educational Resources Information Center

    Florida, Jennifer

    2012-01-01

    The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

  15. Structural crossover from nonmodulated to long-period modulated tetragonal phase and anomalous change in ferroelectric properties in the lead-free piezoelectric N a1 /2B i1 /2Ti O3-BaTi O3

    NASA Astrophysics Data System (ADS)

    Rao, Badari Narayana; Khatua, Dipak Kumar; Garg, Rohini; Senyshyn, Anatoliy; Ranjan, Rajeev

    2015-06-01

    The highly complex structure-property interrelationship in the lead-free piezoelectric (x )N a1 /2B i1 /2Ti O3- (1 -x ) BaTi O3 is a subject of considerable contemporary debate. Using comprehensive x-ray, neutron diffraction, dielectric, and ferroelectric studies, we have shown the existence of a new criticality in this system at x =0.80 , i.e., well within the conventional tetragonal phase field. This criticality manifests as a nonmonotonic variation of the tetragonality and coercivity and is shown to be associated with a crossover from a nonmodulated tetragonal phase (for x <0.8 ) to a long-period modulated tetragonal phase (for x >0.80 ). It is shown that the stabilization of long-period modulation introduces a characteristic depolarization temperature in the system. While differing qualitatively from the two-phase model often suggested for the critical compositions of this system, our results support the view with regard to the tendency in perovskites to stabilize long-period modulated structures as a result of complex interplay of antiferrodistortive modes [Bellaiche and Iniguez, Phys. Rev. B 88, 014104 (2013), 10.1103/PhysRevB.88.014104; Prosandeev, Wang, Ren, Iniguez, ands Bellaiche, Adv. Funct. Mater. 23, 234 (2013), 10.1002/adfm.201201467].

  16. β2-adrenoceptor-induced modulation of transglutaminase 2 transamidase activity in cardiomyoblasts.

    PubMed

    Vyas, Falguni S; Nelson, Carl P; Freeman, Fiona; Boocock, David J; Hargreaves, Alan J; Dickenson, John M

    2017-10-15

    Tissue transglutaminase 2 (TG2) is modulated by protein kinase A (PKA) mediated phosphorylation: however, the precise mechanism(s) of its modulation by G-protein coupled receptors coupled to PKA activation are not fully understood. In the current study we investigated the potential regulation of TG2 activity by the β 2 -adrenoceptor in rat H9c2 cardiomyoblasts. Transglutaminase transamidation activity was assessed using amine-incorporating and protein cross-linking assays. TG2 phosphorylation was determined via immunoprecipitation and Western blotting. The long acting β 2 -adrenoceptor agonist formoterol induced time- and concentration-dependent increases in TG2 transamidation. Increases in TG2 activity were reduced by the TG2 inhibitors Z-DON (Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-L-valinyl-L-prolinyl-L-leucinmethylester) and R283 ((1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride). Responses to formoterol were blocked by pharmacological inhibition of PKA, extracellular signal-regulated kinase 1 and 2 (ERK1/2), or phosphatidylinositol 3-kinase (PI-3K) signalling. Furthermore, the removal of extracellular Ca 2+ also attenuated formoterol-induced TG2 activation. Fluorescence microscopy demonstrated TG2-induced biotin-X-cadaverine incorporation into proteins. Formoterol increased the levels of TG2-associated phosphoserine and phosphothreonine, which were blocked by inhibition of PKA, ERK1/2 or PI-3K signalling. Subsequent proteomic analysis identified known (e.g. lactate dehydrogenase A chain) and novel (e.g. Protein S100-A6) protein substrates for TG2. Taken together, the data obtained suggest that β 2 -adrenoceptor-induced modulation of TG2 represents a novel paradigm in β 2 -adrenoceptor cell signalling, expanding the repertoire of cellular functions responsive to catecholamine stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.

    PubMed

    Reineke, Lucas C; Merrick, William C

    2009-12-01

    Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using DeltaeIF2A yeast. We found that the stability of the stem-loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.

  18. A fixed-jaw method to protect critical organs during intensity-modulated radiotherapy

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

    Chen, Jiayun; Chen, Xinyuan; Huang, Manni, E-mail: dai_jianrong@163.com

    2014-01-01

    Intensity-modulated radiotherapy (IMRT) plays an important role in cancer radiotherapy. For some patients being treated with IMRT, the extremely low tolerances of critical organs (such as lens, ovaries, and testicles) cannot be met during treatment planning. The aim of this article is to introduce a new planning method to overcome that problem. In current planning practice, jaw positions are automatically set to cover all target volumes by the planning system (e.g., Pinnacle{sup 3} system). Because of such settings, critical organs may be fully blocked by the multileaf collimator (MLC), but they still sit in the field that is shaped bymore » collimator jaws. These critical organs receive doses from the transmission and leakage of MLC leaves. We manually fixed jaw positions to block them to further reduce such doses. This method has been used for different treatment sites in our clinic, and it was thoroughly evaluated in patients with radical hysterectomy plus ovarian transposition after surgery. For each patient, 2 treatment plans were designed with the same optimization parameters: the original plan with automatically chosen jaw positions (called O-plan) and the plan with fixed-jaw positions (named F-plan). In the F-plan, the jaws were manually fixed to block the ovaries. For target coverage, the mean conformity index (CI) of the F-plan (1.28 ± 0.02) was remarkably lower than that of the O-plan (1.53 ± 0.09) (p < 0.05). The F-plan and the O-plan performed similarly in target dose homogeneity. Meanwhile, for the critical organ sparing, the mean dose of both ovaries were much lower in the F-plan than that in the O-plan (p < 0.05). The V{sub 20}, V{sub 30}, and V{sub 40} of bladder were also lower in the F-plan (93.57 ± 1.98, 73.99 ± 5.76, and 42.33 ± 3.7, respectively) than those in the O-plan (97.98 ± 1.11, 85.07 ± 4.04, and 49.71 ± 3.63, respectively) (p < 0.05). The maximum dose to the spinal cord planning organ at risk (OAR) volume (PRV) in the O

  19. Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.

    PubMed

    Rasmiena, Aliki A; Barlow, Christopher K; Stefanovic, Nada; Huynh, Kevin; Tan, Ricardo; Sharma, Arpeeta; Tull, Dedreia; de Haan, Judy B; Meikle, Peter J

    2015-12-01

    We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The effectiveness of module with critical thinking approach on hydrolysis and buffer materials in chemistry learning

    NASA Astrophysics Data System (ADS)

    Nuswowati, M.; Purwanti, E.

    2018-03-01

    The research aims is to find out the effectiveness of critical thinking approach in Chemistry learning especially on hydrolysis and buffer materials. The level of its effectiveness was viewed from the students’ learning outcomes including knowledge, attitude and skill domains. The data were collected through validation sheets, questionnaires and tests, which were then analyzed by using descriptive quantitative method. The first step conducted was validating the module that was going to be used in the learning processes. The students’ learning outcome on knowledge domain was very good, viewed from the classical attainment by 88.63% with N-gain 0.718 with high criteria. It was also viewed from the students’ criticality level in solving the given problems. The result of the study revealed that more than 75% of the students obtained critical and very critical criteria in solving the given problems. The students’ attitudes and skills values were viewed through observation sheets during the learning processes. The result of the observation stated that more than 75% of the students showed good and very good attitudes and skills values. Based on the data, it could be concluded that the module with critical thinking approach was effective to be used on hydrolysis and buffer materials.

  1. Anion exchanger 2 is critical for CD8(+) T cells to maintain pHi homeostasis and modulate immune responses.

    PubMed

    Concepcion, Axel R; Salas, January T; Sarvide, Sarai; Sáez, Elena; Ferrer, Alex; López, María; Portu, Ainhoa; Banales, Jesús M; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P J; Prieto, Jesús; Medina, Juan F

    2014-05-01

    Mitogenic stimulation of lymphocytes involves alkalinization of intracellular pH (pHi ). Subsequent pHi regulation may involve HCO3 (-) extrusion through Cl(-) /HCO3 (-) exchangers and/or Na(+) -HCO3 (-) co-transporters with acid-loading capability. Abnormalities in these mechanisms could result in immune dysfunctions, as suggested by the CD8(+) T-cell expansion encountered in mice lacking Ae2 (a widely expressed acid loader with electroneutral and Na(+) -independent Cl(-) /HCO3 (-) anion-exchange activity). Here we report that CD8(+) T cells but not CD4(+) T cells or other lymphocyte populations, are crucially dependent on Ae2 for pHi regulation. While total lymphocytes (including isolated CD4(+) T cells) exhibit Ae1 expression and Na(+) -HCO3 (-) co-transport with acidifying potential, CD8(+) T cells lack these acid-loading mechanisms. In Ae2-KO mice, CD4(+) but not CD8(+) T cells upregulate these potential Ae2 surrogates. As a consequence, Ae2-KO CD8(+) T cells exhibit alkalinized pHi , and dramatically increase their pHi upon CD3 stimulation. Moreover, stimulated Ae2-deficient CD8(+) T cells show enhanced intracellular production of IL-2 and membrane expression of its receptor IL-2Rα, together with increased cell proliferation and activation. These findings demonstrate that CD8(+) T cells are critically dependent on Ae2 for pHi homeostasis and tuning of cell proliferation and activation. Ae2 thus constitutes a novel target to modulate CD8(+) T-cell responses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Improvements in world-wide intercomparison of PV module calibration

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

    Salis, E.; Pavanello, D.; Field, M.

    The calibration of the electrical performance of seven photovoltaic (PV) modules was compared between four reference laboratories on three continents. The devices included two samples in standard and two in high-efficiency crystalline silicon technology, two CI(G)S and one CdTe module. The reference value for each PV module parameter was calculated from the average of the results of all four laboratories, weighted by the respective measurement uncertainties. All single results were then analysed with respect to this reference value using the E n number approach. For the four modules in crystalline silicon technology, the results agreed in general within +/-0.5%, withmore » all values within +/-1% and all E n numbers well within [-1, 1], indicating further scope for reducing quoted measurement uncertainty. Regarding the three thin-film modules, deviations were on average roughly twice as large, i.e. in general from +/-1% to +/-2%. A number of inconsistent results were observable, although within the 5% that can be statistically expected on the basis of the E n number approach. Most inconsistencies can be traced to the preconditioning procedure of one participant, although contribution of other factors cannot be ruled out. After removing these obvious inconsistent results, only two real outliers remained, representing less than 2% of the total number of measurands. The results presented show improved agreement for the calibration of PV modules with respect to previous international exercises. For thin-film PV modules, the preconditioning of the devices prior to calibration measurements is the most critical factor for obtaining consistent results, while the measurement processes seem consistent and repeatable.« less

  3. Improvements in world-wide intercomparison of PV module calibration

    DOE PAGES

    Salis, E.; Pavanello, D.; Field, M.; ...

    2017-09-14

    The calibration of the electrical performance of seven photovoltaic (PV) modules was compared between four reference laboratories on three continents. The devices included two samples in standard and two in high-efficiency crystalline silicon technology, two CI(G)S and one CdTe module. The reference value for each PV module parameter was calculated from the average of the results of all four laboratories, weighted by the respective measurement uncertainties. All single results were then analysed with respect to this reference value using the E n number approach. For the four modules in crystalline silicon technology, the results agreed in general within +/-0.5%, withmore » all values within +/-1% and all E n numbers well within [-1, 1], indicating further scope for reducing quoted measurement uncertainty. Regarding the three thin-film modules, deviations were on average roughly twice as large, i.e. in general from +/-1% to +/-2%. A number of inconsistent results were observable, although within the 5% that can be statistically expected on the basis of the E n number approach. Most inconsistencies can be traced to the preconditioning procedure of one participant, although contribution of other factors cannot be ruled out. After removing these obvious inconsistent results, only two real outliers remained, representing less than 2% of the total number of measurands. The results presented show improved agreement for the calibration of PV modules with respect to previous international exercises. For thin-film PV modules, the preconditioning of the devices prior to calibration measurements is the most critical factor for obtaining consistent results, while the measurement processes seem consistent and repeatable.« less

  4. Potential-induced degradation of Cu(In,Ga)Se2 photovoltaic modules

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Seira; Jonai, Sachiko; Hara, Kohjiro; Komaki, Hironori; Shimizu-Kamikawa, Yukiko; Shibata, Hajime; Niki, Shigeru; Kawakami, Yuji; Masuda, Atsushi

    2015-08-01

    Potential-induced degradation (PID) of Cu(In,Ga)Se2 (CIGS) photovoltaic (PV) modules fabricated from integrated submodules is investigated. PID tests were performed by applying a voltage of -1000 V to connected submodule interconnector ribbons at 85 °C. The normalized energy conversion efficiency of a standard module decreases to 0.2 after the PID test for 14 days. This reveals that CIGS modules suffer PID under this experimental condition. In contrast, a module with non-alkali glass shows no degradation, which implies that the degradation occurs owing to alkali metal ions, e.g., Na+, migrating from the cover glass. The results of dynamic secondary ion mass spectrometry show Na accumulation in the n-ZnO transparent conductive oxide layer of the degraded module. A CIGS PV module with an ionomer (IO) encapsulant instead of a copolymer of ethylene and vinyl acetate shows no degradation. This reveals that the IO encapsulant can prevent PID of CIGS modules. A degraded module can recover from its performance losses by applying +1000 V to connected submodule interconnector ribbons from an Al plate placed on the test module.

  5. Interface Specifications for the A-7E Shared Services Module.

    DTIC Science & Technology

    1982-09-08

    To illustrate the principles, the onboard software for the Navy’s A-7E aircraft will be redesigned and rewritten. The Shared Services module provides...purpose of the Shared Services module is to allow the remainder of the software to remain unchanged when the requirements-based rules for these values and...services change. This report describes the modular structure of the Shared Services module, and contains the abstract interface specifications for all

  6. jsc2018m000130_Orion Crew Module for Ascent Abort-2 Arrives in Houston

    NASA Image and Video Library

    2018-03-08

    Ascent Abort-2 Module Arrives in Houston---------------------------------------------------------- NASA’s Johnson Space Center is the center of activity leading the design and build up for a critical safety test of America’s new exploration spacecraft. An Orion crew module was delivered to Houston last week for assembly and outfitting for the April 2019 Ascent Abort-2 test, to demonstrate the ability of the spacecraft’s Launch Abort System to pull the crew module to safety if an emergency ever arises during ascent to space. Doing this work at JSC is part of a lean approach to development, to minimize cost and schedule risks associated with the test. _______________________________________ FOLLOW ORION! Twitter: https://twitter.com/NASA_Orion/ Facebook: https://www.facebook.com/NASAOrion/ Instagram: https://www.instagram.com/explorenasa/

  7. Development and evaluation of a critical care e-learning scenario.

    PubMed

    Tait, Michael; Tait, Desiree; Thornton, Frances; Edwards, Mark

    2008-11-01

    This paper describes the development and evaluation of a critical care e-learning scenario for student nurses. At present, there are insufficient opportunities in the United Kingdom (UK) for student nurses to experience clinical placements where their skills in care of the critically-ill can be developed. There is therefore a need for new learning materials that help learners recognise the signs of clinical deterioration and rehearse the management of critically-ill patients. One way of meeting this need is by using electronic care scenarios. Several electronic care scenarios have been developed at Swansea University as part of the eWARD project. This article describes the design and evaluation of a critical care scenario that follows the care of a road casualty (John Macadam) after admission to an intensive care unit. The scenario was designed by an advisory team comprising a clinical lecturer and e-learning specialists. After using the scenario, 144 nursing students completed a Web-based questionnaire that collected demographic and attitudinal data for analysis using SPSS. Nursing students had a strongly positive attitude to the scenario with median scores in excess of 20 compared to maxima of 25 for scales measuring ease-of-use, interactivity, realism and confidence. None of the demographic data collected had a significant effect on these attitudes. The positive attitude of student nurses to this scenario strongly supports its use to help learners to (1) acquire knowledge and awareness when real life placements in these settings are not available and (2) extend their knowledge after coming across similar situations in practice.

  8. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control

    PubMed Central

    Jennings, Martin D.; Kershaw, Christopher J.; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P.; Costello, Joseph L.; Donaldson, Ian J.; Zhou, Yu; Pavitt, Graham D.

    2016-01-01

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. PMID:27458202

  9. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

    PubMed

    Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

    2016-11-16

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. 2D materials in electro-optic modulation: energy efficiency, electrostatics, mode overlap, material transfer and integration

    NASA Astrophysics Data System (ADS)

    Ma, Zhizhen; Hemnani, Rohit; Bartels, Ludwig; Agarwal, Ritesh; Sorger, Volker J.

    2018-02-01

    Here we discuss the physics of electro-optic modulators deploying 2D materials. We include a scaling laws analysis and show how energy-efficiency and speed change for three underlying cavity systems as a function of critical device length scaling. A key result is that the energy-per-bit of the modulator is proportional to the volume of the device, thus making the case for submicron-scale modulators possible deploying a plasmonic optical mode. We then show how Graphene's Pauli-blocking modulation mechanism is sensitive to the device operation temperature, whereby a reduction of the temperature enables a 10× reduction in modulator energy efficiency. Furthermore, we show how the high-index tunability of graphene is able to compensate for the small optical overlap factor of 2D-based material modulators, which is unlike classical silicon-based dispersion devices. Lastly, we demonstrate a novel method towards a 2D material printer suitable for cross-contamination free and on-demand printing. The latter paves the way to integrate 2D materials seamlessly into taped-out photonic chips.

  11. eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

    PubMed

    Silva, Bruno M; Barbosa, Thales C; Neves, Fabricia J; Sales, Allan K; Rocha, Natalia G; Medeiros, Renata F; Pereira, Felipe S; Garcia, Vinicius P; Cardoso, Fabiane T; Nobrega, Antonio C L

    2014-12-01

    Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Map3k8 Modulates Monocyte State and Atherogenesis in ApoE-/- Mice.

    PubMed

    Sanz-Garcia, Carlos; Sánchez, Ángela; Contreras-Jurado, Constanza; Cales, Carmela; Barranquero, Cristina; Muñoz, Marta; Merino, Ramón; Escudero, Paula; Sanz, Maria-Jesús; Osada, Jesús; Aranda, Ana; Alemany, Susana

    2017-02-01

    Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R (nucleotide-binding oligomerization domain-like 2R), adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. We show here that Map3k8 deficiency results in smaller numbers of Ly6C high CD11c low and Ly6C low CD11c high monocytes in ApoE - /- mice fed a high-fat diet (HFD). Map3k8 -/- ApoE -/- monocytes displayed high rates of apoptosis and reduced amounts of Nr4a1, a transcription factor known to modulate apoptosis in Ly6C low CD11c high monocytes. Map3k8 -/- ApoE -/- splenocytes and macrophages showed irregular patterns of cytokine and chemokine expression. Map3k8 deficiency altered cell adhesion and migration in vivo and decreased CCR2 expression, a determinant chemokine receptor for monocyte mobilization, on circulating Ly6C high CD11c low monocytes. Map3k8 -/- ApoE -/- mice fed an HFD showed decreased cellular infiltration in the atherosclerotic plaque, with low lipid content. Lesions had similar size after Map3k8 +/+ ApoE -/- bone marrow transplant into Map3k8 -/- ApoE -/- and Map3k8 +/+ ApoE -/- mice fed an HFD, whereas smaller plaques were observed after the transplantation of bone marrow lacking both ApoE and Map3k8. Map3k8 decreases apoptosis of monocytes and enhances CCR2 expression on Ly6C high CD11c low monocytes of ApoE -/- mice fed an HFD. These findings explain the smaller aortic lesions in ApoE -/- mice with Map3k8 -/- ApoE -/- bone marrow cells fed an HFD, supporting further studies of Map3k8 as an antiatherosclerotic target. © 2016 American Heart Association, Inc.

  13. Indirubin-3′-(2,3 dihydroxypropyl)-oximether (E804) is a potent modulator of LPS-stimulated macrophage functions

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

    Babcock, Abigail S.; Anderson, Amy L.; Graduate Program in Environmental Toxicology, Clemson University, Clemson, SC 29634

    2013-01-01

    Indirubin is a deep-red bis-indole isomer of indigo blue, both of which are biologically active ingredients in Danggui Longhui Wan, an ancient Chinese herbal tea mixture used to treat neoplasia and chronic inflammation and to enhance detoxification of xenobiotics. Multiple indirubin derivatives have been synthesized and shown to inhibit cyclin-dependent kinases (CDKs) and glycogen-synthase kinase (GSK-3β) with varying degrees of potency. Several indirubins are also aryl hydrocarbon receptor (AhR) agonists, with AhR-associated activities covering a wide range of potencies, depending on molecular structure. This study examined the effects of indirubin-3′-(2,3 dihydroxypropyl)-oximether (E804), a novel indirubin with potent STAT3 inhibitory properties,more » on basal and LPS-inducible activities in murine RAW264.7 macrophages. Using a focused commercial qRT-PCR array platform (SuperArray®), the effects of E804 on expression of a suite of genes associated with stress and toxicity were determined. Most genes up-regulated by LPS treatment were suppressed by E804; including LPS-induced expression of pro-inflammatory cytokines and receptors, apoptosis control genes, and oxidative stress response genes. Using qRT-PCR as a follow up to the commercial arrays, E804 treatment suppressed LPS-induced COX-2, iNOS, IL-6 and IL-10 gene expression, though the effects on iNOS and COX-2 protein expression were less dramatic. E804 also inhibited LPS-induced secretion of IL-6 and IL-10. Functional endpoints, including iNOS and lysozyme enzymatic activity, phagocytosis of fluorescent latex beads, and intracellular killing of bacteria, were also examined, and in each experimental condition E804 suppressed activities. Collectively, these results indicate that E804 is a potent modulator of pro-inflammatory profiles in LPS-treated macrophages. -- Highlights: ► RAW 264.7 macrophages were treated with 1 μM Indirubin E804, 1 μg/ml LPS, or both. ► E804 suppresses LPS

  14. Interactive E-learning module in pharmacology: a pilot project at a rural medical college in India.

    PubMed

    Gaikwad, Nitin; Tankhiwale, Suresh

    2014-01-01

    Many medical educators are experimenting with innovative ways of E-learning. E-learning provides opportunities to students for self-directed learning in addition to other advantages. In this study, we designed and evaluated an interactive E-learning module in pharmacology for effectiveness, acceptability and feasibility, with the aim of promoting active learning in this fact-filled subject. A quasi-experimental single-group pre-test/post-test study was conducted with fourth-semester students of the second professionals course (II MBBS), selected using non-probability convenience sampling method. An E-learning module in endocrine pharmacology was designed to comprise three units of interactive PowerPoint presentations. The pre-validated presentations were uploaded on the website according to a predefined schedule and the 42 registered students were encouraged to self-learning using these interactive presentations. Cognitive gain was assessed using an online pre- and post-test for each unit. Students' perceptions were recorded using an online feedback questionnaire on a 5-point Likert scale. Finally, focused group discussion was conducted to further explore students' views on E-learning activity. Significant attrition was observed during the E-learning activity. Of the 42 registered students, only 16 students completed the entire E-learning module. The summed average score of all three units (entire module) was increased significantly from 38.42 % (summed average pre-test score: 11.56/30 ± 2.90) to 66.46 % (summed average post-test score: 19.94/30 ± 6.13). The class-average normalized gain for the entire module was 0.4542 (45.42). The students accepted this E-learning activity well as they perceived it to be innovative, convenient, flexible and useful. The average rating was between 4 (agree) and 5 (strongly agree). The interactive E-learning module in pharmacology was moderately effective and well perceived by the students. The simple, cost-effective and

  15. Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches Induced by a Serotonergic Hallucinogen in Mice

    PubMed Central

    Benvenga, Mark J.; Chaney, Stephen F.; Baez, Melvyn; Britton, Thomas C.; Hornback, William J.; Monn, James A.; Marek, Gerard J.

    2018-01-01

    There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT) mice were administered (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and observed for head twitch activity. DOI failed to produce significant head twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM) CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice. Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor potentiator CBiPES was able to attenuate the increase in the HTR produced by LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are consistent with the hypothesis that that DOI-induced head twitches are modulated by mGlu2 receptor activation. These results also are in keeping with a critical autoreceptor function for mGlu2 receptors in the prefrontal cortex with differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2 receptor KO mice). The robust attenuation of DOI-induced head twitches in the mGlu2 receptor KO mice appears to reflect the critical role of glutamate in ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future experiments with inducible knockouts for the mGlu2 receptor and/or selective mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in understanding glutamatergic modulation of prefrontal

  16. Critical success factors for implementing healthcare e-Learning.

    PubMed

    Lee, Te-Shu; Kuo, Mu-Hsing; Borycki, Elizabeth M; Yunyong, David

    2011-01-01

    The use of e-Learning in educational institutes has rapidly increased along with the development of information and communication technology (ICT). In healthcare, more medical educators are using e-Learning to support their curriculum design, delivery and evaluation. However, no systematic work exists on characterizing a collective set of Critical Success Factors (CSFs) for implementing e-Learning in the healthcare education institutions. The aim of this paper is to study the CSFs of implementing healthcare e-Learning.

  17. Analysing Users' Satisfaction with E-Learning Using a Negative Critical Incidents Approach

    ERIC Educational Resources Information Center

    Chen, Nian-Shing; Lin, Kan-Min; Kinshuk

    2008-01-01

    One critical success factor for e-learning is learners' satisfaction with it. This is affected by both positive and negative experiences in a learning process. This paper examines the impact of such critical incidents on learners' satisfaction in e-learning. In particular, frequent occurrence of negative critical incidents has significant…

  18. RCRA, superfund and EPCRA hotline training module. Introduction to: RCRA treatment, storage, and disposal facilities (40 cfr parts 264/265, subparts a-e) updated July 1996

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

    NONE

    1996-07-01

    The management of hazardous waste at treatment, storage, and disposal facilities (TSDFs) plays a large and critical role in the Resource Conservation and Recovery Act (RCRA) regulatory scheme. The training module presents an overview of the general TSDF standards found in 40 CFR Parts 264/265, Subparts A through E.

  19. SU-E-T-624: Quantitative Evaluation of 2D Versus 3D Dosimetry for Stereotactic Volumetric Modulated Arc Delivery Using COMPASS

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

    Vikraman, S; Karrthick, K; Rajesh, T

    2014-06-15

    Purpose: The purpose of this study was to evaluate quantitatively 2D versus 3D dosimetry for stereotactic volumetric modulated arc delivery using COMPASS with 2D array. Methods: Twenty-five patients CT images and RT structures of different sites like brain, head and neck, thorax, abdomen and spine were taken from Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in Cyberknife. For each patient, linac based VMAT stereotactic plans were generated in Monaco TPS v 3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5-20Gy/fraction.TPS calculated VMAT plan delivery accuracy was quantitatively evaluated withmore » COMPASS measured dose and calculated dose based on DVH metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using Multicube. Results: For each site, D{sub 9} {sub 5} was achieved with 100% of prescription dose with maximum 0.05SD. Conformity index (CI) was observed closer to 1.15 in all cases. Maximum deviation of 2.62 % was observed for D{sub 9} {sub 5} when compared TPS versus COMPASS measured. Considerable deviations were observed in head and neck cases compare to other sites. The maximum mean and standard deviation for D{sub 9} {sub 5}, average target dose and average gamma were -0.78±1.72, -1.10±1.373 and 0.39±0.086 respectively. Numbers of pixels passing 2D fluence verification were observed as a mean of 99.36% ±0.455 SD with 3% dose difference and 3mm DTA. For critical organs in head and neck cases, significant dose differences were observed in 3D dosimetry while the target doses were matched well within limit in both 2D and 3D dosimetry. Conclusion: The quantitative evaluations of 2D versus 3D dosimetry for stereotactic volumetric modulated plans showed the potential of highlighting the delivery errors. This study reveals that COMPASS 3D dosimetry is an effective tool for

  20. Spliceosomal protein E regulates neoplastic cell growth by modulating expression of cyclin E/CDK2 and G2/M checkpoint proteins.

    PubMed

    Li, Z; Pützer, B M

    2008-12-01

    Small nuclear ribonucleoproteins are essential splicing factors. We previously identified the spliceosomal protein E (SmE) as a downstream effector of E2F1 in p53-deficient human carcinoma cells. Here, we investigated the biological relevance of SmE in determining the fate of cancer and non-tumourigenic cells. Adenovirus-mediated expression of SmE selectively reduces growth of cancerous cells due to decreased cell proliferation but not apoptosis. A similar growth inhibitory effect for SmD1 suggests that this is a general function of Sm-family members. Deletion of Sm-motifs reveals the importance of the Sm-1 domain for growth suppression. Consistently, SmE overexpression leads to inhibition of DNA synthesis and G2 arrest as shown by BrdU-incorporation and MPM2-staining. Real-time RT-PCR and immunoblotting showed that growth arrest by SmE directly correlates with the reduction of cyclin E, CDK2, CDC25C and CDC2 expression, and up-regulation of p27Kip. Importantly, SmE activity was not associated with enhanced expression of other spliceosome components such as U1 SnRNP70, suggesting that the growth inhibitory effect of SmE is distinct from its pre-mRNA splicing function. Furthermore, specific inactivation of SmE by shRNA significantly increased the percentage of cells in S phase, whereas the amount of G2/M arrested cells was reduced. Our data provide evidence that Sm proteins function as suppressors of tumour cell growth and may have major implications as cancer therapeutics.

  1. Cooperative Learning and Web 2.0: A Social Perspective on Critical Thinking

    ERIC Educational Resources Information Center

    Schipke, Rae Carrington

    2018-01-01

    This article discusses how cooperative learning as a socioinstructional approach, relates to both socially-based emerging technologies (i.e. Web 2.0) and to critical thinking with respect to co-cognition. It begins with a discussion of the importance of connecting cooperative learning, Web 2.0, and critical thinking. This is followed by the need…

  2. Implementing the CASPiE course-based research experience at the United States Military Academy: Affective responses and effects on critical thinking

    NASA Astrophysics Data System (ADS)

    Chase, Anthony Michael

    The Center for Authentic Science Practices in Education (CASPiE) pioneered a course-based research experience approach to teaching chemistry laboratory courses. The method had previously been studied in a variety of institutional settings. Recently, the United States Military Academy at West Point decided to develop CASPiE-style modules for the introductory honors chemistry course. This research setting presents clean experimental-control comparisons and a group of faculty who were completely new to the method. Equipping students with authentic research experiences early in their education is important regardless of the institution. However, cadets at a military academy must make decisions relatively early (the outset of their second year) as to what their career trajectory will be as eventual officers. In the new CASPiE-based experience, cadets are given the opportunity to select from one of three different modules (analytical chemistry, toxicology, and chemical engineering) in which to participate during the course. These three modules represent subsections of an overall Army waste-to-energy research project. Cadets generate unique hypotheses, real data, and research posters towards the advancement of the project. Posters are then presented in a session. that includes an audience of project stakeholders, course instructors, and other academy faculty and staff. Here, I will present my research methods, evaluative procedures, and findings in the affective domain, critical thinking, and laboratory content comprehension.

  3. Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety.

    PubMed

    Bedse, Gaurav; Hartley, Nolan D; Neale, Emily; Gaulden, Andrew D; Patrick, Toni A; Kingsley, Philip J; Uddin, Md Jashim; Plath, Niels; Marnett, Lawrence J; Patel, Sachin

    2017-10-01

    Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood. We utilized pharmacological augmentation and depletion combined with behavioral and electrophysiological approaches to probe the role of 2-AG signaling in the modulation of stress-induced anxiety and the functional redundancy between AEA and 2-AG signaling in the modulation of anxiety-like behaviors in mice. Selective 2-AG augmentation reduced anxiety in the light/dark box assay and prevented stress-induced increases in anxiety associated with limbic AEA deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors, which was normalized by selective pharmacological augmentation of AEA signaling and via direct cannabinoid receptor 1 stimulation with Δ 9 -tetrahydrocannabinol. Electrophysiological studies revealed 2-AG modulation of amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic effects of 2-AG augmentation. Although AEA and 2-AG likely subserve distinct physiological roles, a pharmacological and functional redundancy between these canonical eCB signaling pathways exists in the modulation of anxiety-like behaviors. These data support development of eCB-based treatment approaches for mood and anxiety disorders and suggest a potentially wider therapeutic overlap between AEA and 2-AG augmentation approaches than was previously appreciated. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial.

    PubMed

    Morgulis, Yuri; Kumar, Rakesh K; Lindeman, Robert; Velan, Gary M

    2012-05-28

    e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group's evaluation of the module was overwhelmingly positive. A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  5. Ability of the bed bug (Hemiptera: Cimicidae) defensive secretions (E)-2-hexenal and (E)-2-octenal to attract adult bed bugs

    USDA-ARS?s Scientific Manuscript database

    Accurate and timely surveillance of bed bug infestations is critical for development of effective control strategies. While the bed bug produced volatiles (E)-2-hexenal and (E)-2-octenal are considered defensive secretions, through use of EthoVision® video-tracking software we demonstrate that low ...

  6. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    PubMed Central

    2012-01-01

    Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines. PMID:22640463

  7. Ribonuclease E modulation of the bacterial SOS response.

    PubMed

    Manasherob, Robert; Miller, Christine; Kim, Kwang-sun; Cohen, Stanley N

    2012-01-01

    Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes-leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed.

  8. Ribonuclease E Modulation of the Bacterial SOS Response

    PubMed Central

    Manasherob, Robert; Miller, Christine; Kim, Kwang-sun; Cohen, Stanley N.

    2012-01-01

    Plants, animals, bacteria, and Archaea all have evolved mechanisms to cope with environmental or cellular stress. Bacterial cells respond to the stress of DNA damage by activation of the SOS response, the canonical RecA/LexA-dependent signal transduction pathway that transcriptionally derepresses a multiplicity of genes–leading to transient arrest of cell division and initiation of DNA repair. Here we report the previously unsuspected role of E. coli endoribonuclease RNase E in regulation of the SOS response. We show that RNase E deletion or inactivation of temperature-sensitive RNase E protein precludes normal initiation of SOS. The ability of RNase E to regulate SOS is dynamic, as down regulation of RNase E following DNA damage by mitomycin C resulted in SOS termination and restoration of RNase E function leads to resumption of a previously aborted response. Overexpression of the RraA protein, which binds to the C-terminal region of RNase E and modulates the actions of degradosomes, recapitulated the effects of RNase E deficiency. Possible mechanisms for RNase E effects on SOS are discussed. PMID:22719885

  9. Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes.

    PubMed

    Vallerie, Sara N; Kramer, Farah; Barnhart, Shelley; Kanter, Jenny E; Breyer, Richard M; Andreasson, Katrin I; Bornfeldt, Karin E

    2016-01-01

    Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis.

  10. Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes

    PubMed Central

    Vallerie, Sara N.; Kramer, Farah; Barnhart, Shelley; Kanter, Jenny E.; Breyer, Richard M.; Andreasson, Katrin I.; Bornfeldt, Karin E.

    2016-01-01

    Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis. PMID:27351842

  11. Undergraduate teaching modules featuring geodesy data applied to critical social topics (GETSI: GEodetic Tools for Societal Issues)

    NASA Astrophysics Data System (ADS)

    Pratt-Sitaula, B. A.; Walker, B.; Douglas, B. J.; Charlevoix, D. J.; Miller, M. M.

    2015-12-01

    The GETSI project, funded by NSF TUES, is developing and disseminating teaching and learning materials that feature geodesy data applied to critical societal issues such as climate change, water resource management, and natural hazards (serc.carleton.edu/getsi). It is collaborative between UNAVCO (NSF's geodetic facility), Mt San Antonio College, and Indiana University. GETSI was initiated after requests by geoscience faculty for geodetic teaching resources for introductory and majors-level students. Full modules take two weeks but module subsets can also be used. Modules are developed and tested by two co-authors and also tested in a third classroom. GETSI is working in partnership with the Science Education Resource Center's (SERC) InTeGrate project on the development, assessment, and dissemination to ensure compatibility with the growing number of resources for geoscience education. Two GETSI modules are being published in October 2015. "Ice mass and sea level changes" includes geodetic data from GRACE, satellite altimetry, and GPS time series. "Imaging Active Tectonics" has students analyzing InSAR and LiDAR data to assess infrastructure earthquake vulnerability. Another three modules are in testing during fall 2015 and will be published in 2016. "Surface process hazards" investigates mass wasting hazard and risk using LiDAR data. "Water resources and geodesy" uses GRACE, vertical GPS, and reflection GPS data to have students investigating droughts in California and the High Great Plains. "GPS, strain, and earthquakes" helps students learn about infinitesimal and coseismic strain through analysis of horizontal GPS data and includes an extension module on the Napa 2014 earthquake. In addition to teaching resources, the GETSI project is compiling recommendations on successful development of geodesy curricula. The chief recommendations so far are the critical importance of including scientific experts in the authorship team and investing significant resources in

  12. 47 CFR 2.1047 - Measurements required: Modulation characteristics.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Measurements required: Modulation characteristics. 2.1047 Section 2.1047 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY... Certification § 2.1047 Measurements required: Modulation characteristics. (a) Voice modulated communication...

  13. 47 CFR 2.1047 - Measurements required: Modulation characteristics.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Measurements required: Modulation characteristics. 2.1047 Section 2.1047 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY... Certification § 2.1047 Measurements required: Modulation characteristics. (a) Voice modulated communication...

  14. Encapsulation and backsheet adhesion metrology for photovoltaic modules

    DOE PAGES

    Tracy, Jared; Bosco, Nick; Novoa, Fernando; ...

    2016-09-26

    Photovoltaic modules are designed to operate for decades in terrestrial environments. However, mechanical stress, moisture, and ultraviolet radiation eventually degrade protective materials in modules, particularly their adhesion properties, eventually leading to reduced solar cell performance. Despite the significance of interfacial adhesion to module durability, currently there is no reliable technique for characterizing module adhesion properties. We present a simple and reproducible metrology for characterizing adhesion in photovoltaic modules that is grounded in fundamental concepts of beam and fracture mechanics. Using width-tapered cantilever beam fracture specimens, interfacial adhesion was evaluated on relevant interfaces of encapsulation and backsheet structures of new andmore » 27-year-old historic modules. The adhesion energy, Gc [J/m 2], was calculated from the critical value of the strain energy release rate, G, using G = βP2, where β (a mechanical and geometric parameter of the fracture specimen) and P (the experimentally measured critical load) are constants. Under some circumstances where testing may result in cracking of brittle layers in the test specimen, measurement of the delamination length in addition to the critical load was necessary to determine G. Relative to new module materials, backsheet adhesion was 95% and 98% lower for historic modules that were exposed (operated in the field) and unexposed (stored on-site, but out of direct sunlight), respectively. Encapsulation adhesion was 87-94% lower in the exposed modules and 31% lower in the unexposed module. As a result, the metrology presented here can be used to improve module materials and assess long-term reliability.« less

  15. e-Healthcare in India: critical success factors for sustainable health systems.

    PubMed

    Taneja, Udita; Sushil

    2007-01-01

    As healthcare enterprises seek to move towards an integrated, sustainable healthcare delivery model an IT-enabled or e-Healthcare strategy is being increasingly adopted. In this study we identified the critical success factors influencing the effectiveness of an e-Healthcare strategy in India. The performance assessment criteria used to measure effectiveness were increasing reach and reducing cost of healthcare delivery. A survey of healthcare providers was conducted. Analytic Hierarchy Process (AHP) and Interpretive Structural Modeling (ISM) were the analytical tools used to determine the relative importance of the critical success factors in influencing effectiveness of e-Healthcare and their interplay with each other. To succeed in e-Healthcare initiatives the critical success factors that need to be in place are appropriate government policies, literacy levels, and telecommunications and power infrastructure in the country. The focus should not be on the IT tools and biomedical engineering technologies as is most often the case. Instead the nontechnology factors such as healthcare provider and consumer mindsets should be addressed to increase acceptance of, and enhance the effectiveness of, sustainable e-Healthcare services.

  16. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.

    PubMed

    Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

    2015-10-01

    Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53(-/-) mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy.

  17. Advanced intensity-modulation continuous-wave lidar techniques for ASCENDS CO2 column measurements

    NASA Astrophysics Data System (ADS)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. W.; Obland, Michael D.; Meadows, Byron

    2015-10-01

    Global atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity- Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud contamination. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby eliminating the need to correct for sidelobe bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. A comparison of BPSK and linear swept-frequency is also discussed in this paper. These results are extended to include Richardson-Lucy deconvolution techniques to extend the resolution of the lidar beyond that implied by limit of the bandwidth of the modulation, where it is shown useful for making tree canopy measurements.

  18. Advanced Intensity-Modulation Continuous-Wave Lidar Techniques for ASCENDS O2 Column Measurements

    NASA Technical Reports Server (NTRS)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. Wallace; Obland, Michael D.; Meadows, Byron

    2015-01-01

    Global atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity- Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud contamination. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby eliminating the need to correct for sidelobe bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. A comparison of BPSK and linear swept-frequency is also discussed in this paper. These results are extended to include Richardson-Lucy deconvolution techniques to extend the resolution of the lidar beyond that implied by limit of the bandwidth of the modulation, where it is shown useful for making tree canopy measurements.

  19. Pairwise domain adaptation module for CNN-based 2-D/3-D registration.

    PubMed

    Zheng, Jiannan; Miao, Shun; Jane Wang, Z; Liao, Rui

    2018-04-01

    Accurate two-dimensional to three-dimensional (2-D/3-D) registration of preoperative 3-D data and intraoperative 2-D x-ray images is a key enabler for image-guided therapy. Recent advances in 2-D/3-D registration formulate the problem as a learning-based approach and exploit the modeling power of convolutional neural networks (CNN) to significantly improve the accuracy and efficiency of 2-D/3-D registration. However, for surgery-related applications, collecting a large clinical dataset with accurate annotations for training can be very challenging or impractical. Therefore, deep learning-based 2-D/3-D registration methods are often trained with synthetically generated data, and a performance gap is often observed when testing the trained model on clinical data. We propose a pairwise domain adaptation (PDA) module to adapt the model trained on source domain (i.e., synthetic data) to target domain (i.e., clinical data) by learning domain invariant features with only a few paired real and synthetic data. The PDA module is designed to be flexible for different deep learning-based 2-D/3-D registration frameworks, and it can be plugged into any pretrained CNN model such as a simple Batch-Norm layer. The proposed PDA module has been quantitatively evaluated on two clinical applications using different frameworks of deep networks, demonstrating its significant advantages of generalizability and flexibility for 2-D/3-D medical image registration when a small number of paired real-synthetic data can be obtained.

  20. Critical Success Factors for E-Learning Acceptance: Confirmatory Factor Models

    ERIC Educational Resources Information Center

    Selim, Hassan M.

    2007-01-01

    E-learning, one of the tools emerged from information technology, has been integrated in many university programs. There are several factors that need to be considered while developing or implementing university curriculums that offer e-learning based courses. This paper is intended to specify e-learning critical success factors (CSFs) as…

  1. The amino-terminus of the hepatitis C virus (HCV) p7 viroporin and its cleavage from glycoprotein E2-p7 precursor determine specific infectivity and secretion levels of HCV particle types

    PubMed Central

    Denolly, Solène; Bourlet, Thomas; Amirache, Fouzia

    2017-01-01

    Viroporins are small transmembrane proteins with ion channel activities modulating properties of intracellular membranes that have diverse proviral functions. Hepatitis C virus (HCV) encodes a viroporin, p7, acting during assembly, envelopment and secretion of viral particles (VP). HCV p7 is released from the viral polyprotein through cleavage at E2-p7 and p7-NS2 junctions by signal peptidase, but also exists as an E2p7 precursor, of poorly defined properties. Here, we found that ectopic p7 expression in HCVcc-infected cells reduced secretion of particle-associated E2 glycoproteins. Using biochemical assays, we show that p7 dose-dependently slows down the ER-to-Golgi traffic, leading to intracellular retention of E2, which suggested that timely E2p7 cleavage and p7 liberation are critical events to control E2 levels. By studying HCV mutants with accelerated E2p7 processing, we demonstrate that E2p7 cleavage controls E2 intracellular expression and secretion levels of nucleocapsid-free subviral particles and infectious virions. In addition, our imaging data reveal that, following p7 liberation, the amino-terminus of p7 is exposed towards the cytosol and coordinates the encounter between NS5A and NS2-based assembly sites loaded with E1E2 glycoproteins, which subsequently leads to nucleocapsid envelopment. We identify punctual mutants at p7 membrane interface that, by abrogating NS2/NS5A interaction, are defective for transmission of infectivity owing to decreased secretion of core and RNA and to increased secretion of non/partially-enveloped particles. Altogether, our results indicate that the retarded E2p7 precursor cleavage is essential to regulate the intracellular and secreted levels of E2 through p7-mediated modulation of the cell secretory pathway and to unmask critical novel assembly functions located at p7 amino-terminus. PMID:29253880

  2. Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

    DOE PAGES

    Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira; ...

    2015-10-15

    Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [ 11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiBmore » SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.« less

  3. Intensity Modulation Techniques for Continuous-Wave Lidar for Column CO2 Measurements

    NASA Astrophysics Data System (ADS)

    Campbell, J. F.; Lin, B.; Obland, M. D.; Kooi, S. A.; Fan, T. F.; Meadows, B.; Browell, E. V.; Erxleben, W. H.; McGregor, D.; Dobler, J. T.; Pal, S.; O'Dell, C.

    2017-12-01

    Global and regional atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission and the Atmospheric Carbon and Transport (ACT) - America project are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity-Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space and airborne platforms to meet the ASCENDS and ACT-America science measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) and Linear Swept Frequency modulations to uniquely discriminate surface lidar returns from intermediate aerosol and cloud returns. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby eliminating bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that take advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques and provides very high (at sub-meter level) range resolution. We compare BPSK to linear swept frequency and introduce a new technique to eliminate sidelobes in situations from linear swept frequency where the SNR is high with results that rival BPSK. We also investigate the effects of non-linear modulators, which can in some circumstances degrade the orthogonality of the waveforms, and show how to avoid this. These techniques are used in a new data processing architecture written in

  4. Vitamin E Isoforms as Modulators of Lung Inflammation

    PubMed Central

    Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

    2013-01-01

    Asthma and allergic diseases are complex conditions caused by a combination of genetic and environmental factors. Clinical studies suggest a number of protective dietary factors for asthma, including vitamin E. However, studies of vitamin E in allergy commonly result in seemingly conflicting outcomes. Recent work indicates that allergic inflammation is inhibited by supplementation with the purified natural vitamin E isoform α-tocopherol but elevated by the isoform γ-tocopherol when administered at physiological tissue concentrations. In this review, we discuss opposing regulatory effects of α-tocopherol and γ-tocopherol on allergic lung inflammation in clinical trials and in animal studies. A better understanding of the differential regulation of inflammation by isoforms of vitamin E provides a basis towards the design of clinical studies and diets that would effectively modulate inflammatory pathways in lung disease. PMID:24184873

  5. SU-E-T-550: Modulation Index for VMAT

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

    Park, J; Park, S; Kim, J

    2015-06-15

    Purpose: To present modulation indices (MIs) for volumetric modulated arc therapy (VMAT). Methods: A total of 40 VMAT plans were retrospectively selected. To investigate the delivery accuracy of each VMAT plan, gamma passing rates, differences in modulating parameters between plans and log files, and differences between the original plans and the plans reconstructed with the log files were acquired. A modulation index (MIt) was designed by multiplications of the weighted quantifications of MLC speeds, MLC accelerations, gantry accelerations and dose-rate variations. Textural features including angular second moment, inverse difference moment, contrast, variance, correlation and entropy were calculated from the fluencesmore » of each VMAT plan. To test the performance of suggested MIs, Spearman’s rank correlation coefficients (r) with the plan delivery accuracy were calculated. Conventional modulation indices for VMAT including the modulation complexity score for VMAT (MCSv), leaf travel modulation complexity score (LTMCS) and MI by Li & Xing were calculated, and their correlations were also analyzed in the same way. Results: The r values of contrast (particular displacement distance, d = 1), variance (d = 1), MIt, MCSv, LTMCS and MI by Li&Xing to the local gamma passing rates with 2%/2 mm were 0.547 (p < 0.001), 0.519 (p < 0.001), −0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and −0.455 (p = 0.003), respectively. The r values of those to the MLC errors were −0.863, −0.828, 0.917, −0.635, − 0.857 and 0.795, respectively (p < 0.001). For dose-volumetric parameters, MIt showed higher statistically significant correlations than did the conventional modulation indices. Conclusion: The MIt, contrast (d = 1) and variance (d = 1) showed good performance to predict the VMAT delivery accuracy showing higher correlations to the results of various types of verification methods for VMAT. This work was in part supported by the National Research

  6. Advanced Intensity-Modulation Continuous-Wave Lidar Techniques for Column CO2 Measurements

    NASA Astrophysics Data System (ADS)

    Campbell, J. F.; Lin, B.; Nehrir, A. R.; Obland, M. D.; Liu, Z.; Browell, E. V.; Chen, S.; Kooi, S. A.; Fan, T. F.

    2015-12-01

    Global and regional atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission and Atmospheric Carbon and Transport (ACT) - America airborne investigation are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity-Modulated Continuous-Wave (IM-CW) lidar techniques are being investigated as a means of facilitating CO2 measurements from space and airborne platforms to meet the mission science measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud returns. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of intervening optically thin clouds, thereby minimizing bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the Earth's surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. This approach works well for both BPSK and linear swept-frequency modulation techniques and provides very high (at sub-meter level) range resolution. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. A comparison of BPSK and linear swept-frequency is also discussed in this paper. These techniques are used in a new data processing architecture to support the ASCENDS CarbonHawk Experiment Simulator (ACES) and ACT-America programs.

  7. NPY2-receptor variation modulates iconic memory processes.

    PubMed

    Arning, Larissa; Stock, Ann-Kathrin; Kloster, Eugen; Epplen, Jörg T; Beste, Christian

    2014-08-01

    Sensory memory systems are modality-specific buffers that comprise information about external stimuli, which represent the earliest stage of information processing. While these systems have been the subject of cognitive neuroscience research for decades, little is known about the neurobiological basis of sensory memory. However, accumulating evidence suggests that the glutamatergic system and systems influencing glutamatergic neural transmission are important. In the current study we examine if functional promoter variations in neuropeptide Y (NPY) and its receptor gene NPY2R affect iconic memory processes using a partial report paradigm. We found that iconic memory decayed much faster in individuals carrying the rare promoter NPY2R G allele which is associated with increased expression of the Y2 receptor. Possibly this effect is due to altered presynaptic inhibition of glutamate release, known to be modulated by Y2 receptors. Altogether, our results provide evidence that the functionally relevant single nucleotide polymorphism (SNP) in the NPY2R promoter gene affect circumscribed processes of early sensory processing, i.e. only the stability of information in sensory memory buffers. This leads us to suggest that especially the stability of information in sensory memory buffers depends on glutamatergic neural transmission and factors modulating glutamatergic turnover. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  8. Processing and characterization of device solder interconnection and module attachment for power electronics modules

    NASA Astrophysics Data System (ADS)

    Haque, Shatil

    This research is focused on the processing of an innovative three-dimensional packaging architecture for power electronics building blocks with soldered device interconnections and subsequent characterization of the module's critical interfaces. A low-cost approach termed metal posts interconnected parallel plate structure (MPIPPS) was developed for packaging high-performance modules of power electronics building blocks (PEBB). The new concept implemented direct bonding of copper posts, not wire bonding of fine aluminum wires, to interconnect power devices as well as joining the different circuit planes together. We have demonstrated the feasibility of this packaging approach by constructing PEBB modules (consisting of Insulated Gate Bipolar Transistors (IGBTs), diodes, and a few gate driver elements and passive components). In the 1st phase of module fabrication with IGBTs with Si3N 4 passivation, we had successfully fabricated packaged devices and modules using the MPIPPS technique. These modules were tested electrically and thermally, and they operated at pulse-switch and high power stages up to 6kW. However, in the 2nd phase of module fabrication with polyimide passivated devices, we experienced significant yield problems due to metallization difficulties of these devices. The under-bump metallurgy scheme for the development of a solderable interface involved sputtering of Ti-Ni-Cu and Cr-Cu, and an electroless deposition of Zn-Ni-Au metallization. The metallization process produced excellent yield in the case of Si3N4 passivated devices. However, under the same metallization schemes, devices with a polyimide passivation exhibited inconsistent electrical contact resistance. We found that organic contaminants such as hydrocarbons remain in the form of thin monolayers on the surface, even in the case of as-received devices from the manufacturer. Moreover, in the case of polyimide passivated devices, plasma cleaning introduced a few carbon constituents on the

  9. Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

    DTIC Science & Technology

    1994-05-01

    lipopolysaccharide- and TNF-induced cartilage breakdown in bovine nasal cartilage(121’. The use of medications that modulate PGE2 production may have an adverse...Levine, P. Goldhaber. 1972. Evidence that the bone resorption stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2. J. Exp. Med

  10. MYC2 Differentially Modulates Diverse Jasmonate-Dependent Functions in Arabidopsis[W

    PubMed Central

    Dombrecht, Bruno; Xue, Gang Ping; Sprague, Susan J.; Kirkegaard, John A.; Ross, John J.; Reid, James B.; Fitt, Gary P.; Sewelam, Nasser; Schenk, Peer M.; Manners, John M.; Kazan, Kemal

    2007-01-01

    The Arabidopsis thaliana basic helix-loop-helix Leu zipper transcription factor (TF) MYC2/JIN1 differentially regulates jasmonate (JA)-responsive pathogen defense (e.g., PDF1.2) and wound response (e.g., VSP) genes. In this study, genome-wide transcriptional profiling of wild type and mutant myc2/jin1 plants followed by functional analyses has revealed new roles for MYC2 in the modulation of diverse JA functions. We found that MYC2 negatively regulates Trp and Trp-derived secondary metabolism such as indole glucosinolate biosynthesis during JA signaling. Furthermore, MYC2 positively regulates JA-mediated resistance to insect pests, such as Helicoverpa armigera, and tolerance to oxidative stress, possibly via enhanced ascorbate redox cycling and flavonoid biosynthesis. Analyses of MYC2 cis binding elements and expression of MYC2-regulated genes in T-DNA insertion lines of a subset of MYC2–regulated TFs suggested that MYC2 might modulate JA responses via differential regulation of an intermediate spectrum of TFs with activating or repressing roles in JA signaling. MYC2 also negatively regulates its own expression, and this may be one of the mechanisms used in fine-tuning JA signaling. Overall, these results provide new insights into the function of MYC2 and the transcriptional coordination of the JA signaling pathway. PMID:17616737

  11. 47 CFR 2.1513 - Measurements of modulation characteristics.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Measurements of modulation characteristics. 2.1513 Section 2.1513 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS... Measurements of modulation characteristics. (a) Set-up. Test of modulation characteristics are to be performed...

  12. 47 CFR 2.1513 - Measurements of modulation characteristics.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Measurements of modulation characteristics. 2.1513 Section 2.1513 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY ALLOCATIONS... Measurements of modulation characteristics. (a) Set-up. Test of modulation characteristics are to be performed...

  13. Swap intensified WDR CMOS module for I2/LWIR fusion

    NASA Astrophysics Data System (ADS)

    Ni, Yang; Noguier, Vincent

    2015-05-01

    The combination of high resolution visible-near-infrared low light sensor and moderate resolution uncooled thermal sensor provides an efficient way for multi-task night vision. Tremendous progress has been made on uncooled thermal sensors (a-Si, VOx, etc.). It's possible to make a miniature uncooled thermal camera module in a tiny 1cm3 cube with <1W power consumption. For silicon based solid-state low light CCD/CMOS sensors have observed also a constant progress in terms of readout noise, dark current, resolution and frame rate. In contrast to thermal sensing which is intrinsic day&night operational, the silicon based solid-state sensors are not yet capable to do the night vision performance required by defense and critical surveillance applications. Readout noise, dark current are 2 major obstacles. The low dynamic range at high sensitivity mode of silicon sensors is also an important limiting factor, which leads to recognition failure due to local or global saturations & blooming. In this context, the image intensifier based solution is still attractive for the following reasons: 1) high gain and ultra-low dark current; 2) wide dynamic range and 3) ultra-low power consumption. With high electron gain and ultra low dark current of image intensifier, the only requirement on the silicon image pickup device are resolution, dynamic range and power consumption. In this paper, we present a SWAP intensified Wide Dynamic Range CMOS module for night vision applications, especially for I2/LWIR fusion. This module is based on a dedicated CMOS image sensor using solar-cell mode photodiode logarithmic pixel design which covers a huge dynamic range (> 140dB) without saturation and blooming. The ultra-wide dynamic range image from this new generation logarithmic sensor can be used directly without any image processing and provide an instant light accommodation. The complete module is slightly bigger than a simple ANVIS format I2 tube with <500mW power consumption.

  14. Modified Coulomb-Dipole Theory for 2e Photoionization

    NASA Technical Reports Server (NTRS)

    2004-01-01

    In the light of recent experiment on 2e photoionization of Li near threshold, we have considered a modification of the Coulomb-dipole theory, retaining the basic assumption that the threshold is dominated by asymmetric events in phase space [implies r(sub 1), k(sub 1)) greater than or equal to 2(r(sub 2), k(sub )]. In this region [in a collinear model, 2/r(sub 12) approached + 2/(r(sub 1)+r(sub 2)] the interaction reduces to V(rIsub 1) is greater than or equal to 2r(sub 2) is identically equal to [(-Z/r(sub 2)-(A-1)/r(sub 1)] + [(-2r(sub 2)/r(sub 1 exp 2)] is identically equal to V(sub c)+[V(sub d)]. For two electron emission Z = 2, thus both electrons see a Coulomb potential (V(sub c)) asymptotically, albeit each seeing a different charge. The residual potential (V(sub d)) is dipole in character. Writing the total psi = psi (sub c) + psi(sub d) = delta psi, and noting that. (T+V(sub c)-E)psy(sub c) = 0 and (T+V(sub c))psi(sub d) = 0 can be solved exactly, we find, substituting psi into the complete Schrod. Eq., that delta psi = -(H-E)(exp -1)(V(sub d) psi(sub 0)+V(sub c psi (sub 1). Using the fact that the absolute value of V(sub c) is much more than the absolute value of V(sub d) in almost all of configuration space, we can replace H by H(sub 0) in 9H-E)(exp -1) to obtain an improved approximation psi (improved) = psi(sub c) + psi(sub d) -(H(sub 0)-E)(exp -1) (V(sub c) psi (sub 0) + V(sub c) psi(sub 1). Here's the Green's function (H(sub 0)-E)(exp -1), can be exhibited explicitly, but the last term in psi (improved) is small, compared to the first two terms. Inserting them into the transition matrix element, which one handles in the usual way, we obtain in the limit E approaches 0, the threshold law: Q(E) alpha E + M(E)E(exp 5/4) + higher order (Eq. 1a). The modulation function, M(E), is a well-defined (but very non-trivial integral, but it is expected to be well approximated by a sinusoidal function containing a dipole phase term (M(E) = c sin[alpha log (E

  15. RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment

    DOE PAGES

    Hodge, Curtis D.; Ismail, Ismail H.; Edwards, Ross A.; ...

    2016-02-22

    DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. In this paper, we defined the activated RNF8-Ubc13~ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13more » active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. Finally, these findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment.« less

  16. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses.

    PubMed

    Chiurchiù, Valerio; Leuti, Alessandro; Dalli, Jesmond; Jacobsson, Anders; Battistini, Luca; Maccarrone, Mauro; Serhan, Charles N

    2016-08-24

    Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. Copyright © 2016, American Association for the Advancement of Science.

  17. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution

    PubMed Central

    Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

    2015-01-01

    Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53−/− mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy. PMID:25656653

  18. Designing an Affordable Usability Test for E-Learning Modules

    ERIC Educational Resources Information Center

    O'Bryan, Corliss A.; Johnson, Donald M.; Shores-Ellis, Katrina D.; Crandall, Philip G.; Marcy, John A.; Seideman, Steve C.; Ricke, Steven C.

    2010-01-01

    This article provides background and an introduction to a user-centered design and usability test in an inexpensive format that allows content experts who are novices in e-learning development to perform testing on newly developed technical training modules prior to their release. The use of a small number of test participants, avoidance of…

  19. Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer

    PubMed Central

    Sen, Prakriti; Ganguly, Pooja; Ganguly, Niladri

    2018-01-01

    Human papillomaviruses (HPVs) are double stranded circular DNA viruses that infect cutaneous and mucosal epithelial cells. Almost 99% of cervical cancer has a HPV infection. The early oncoproteins E6 and E7 are important in this cellular transformation process. Epigenetic mechanisms have long been known to result in decisive alterations in DNA, leading to alterations in DNA-protein interactions, alterations in chromatin structure and compaction and significant alterations in gene expression. The enzymes responsible for these epigenetic modifications are DNA methyl transferases (DNMTs), histone acetylases and deacetylases. Epigenetics has an important role in cancer development by modifying the cellular micro environment. In this review, the authors discuss the role of HPV oncoproteins E6 and E7 in modulating the epigenetic mechanisms inside the host cell. The oncoproteins induce the expression of DNMTs which lead to aberrant DNA methylations and disruption of the normal epigenetic processes. The E7 oncoprotein may additionally directly bind and induce methyl transferase activity of the enzyme. These modulations lead to altered gene expression levels, particularly the genes involved in apoptosis, cell cycle and cell adhesion. In addition, the present review discusses how epigenetic mechanisms may be targeted for possible therapeutic interventions for HPV mediated cervical cancer. PMID:29285184

  20. An ELMO2-RhoG-ILK network modulates microtubule dynamics

    PubMed Central

    Jackson, Bradley C.; Ivanova, Iordanka A.; Dagnino, Lina

    2015-01-01

    ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin–dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca2+-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. PMID:25995380

  1. Environmental testing of block 2 solar cell modules

    NASA Technical Reports Server (NTRS)

    Griffith, J. S.

    1979-01-01

    The testing procedures and results of samples of the LSA Project Block 2 procurement of silicon solar cell modules are described. Block 2 was the second large scale procurement of silicon solar cell modules made by the JPL Low-cost Solar Array Project with deliveries in 1977 and early 1978. The results showed that the Block 2 modules were greatly improved over Block 1 modules. In several cases it was shown that design improvements were needed to reduce environmental test degradation. These improvements were incorporated during this production run.

  2. MODULATION OF RAT LEYDIG CELL STEROIDOGENIC FUNCTION BY DI(2-ETHYLHEXYL)PHTHALATE

    EPA Science Inventory

    Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate.

    Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, Zirkin BR, Hardy MP.

    Center for Biomedical Research, Population Council, New York, New York 10021, USA. benson@popcbr...

  3. Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia

    PubMed Central

    Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia; Risso, Guillermo; Srebrow, Anabella; Alfaro, Jennifer; Colman-Lerner, Alejandro

    2013-01-01

    The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate. PMID:23922774

  4. Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling

    PubMed Central

    Joo, Adriane; Long, Roger; Cheng, Zhiqiang; Alexander, Courtney; Chang, Wenhan; Klein, Ophir D.

    2016-01-01

    Skeletal development is regulated by the coordinated activity of signaling molecules that are both produced locally by cartilage and bone cells and also circulate systemically. During embryonic development and postnatal bone remodeling, receptor tyrosine kinase (RTK) superfamily members play critical roles in the proliferation, survival, and differentiation of chondrocytes, osteoblasts, osteoclasts, and other bone cells. Recently, several molecules that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1–4). We report that Spry2 plays an important role in regulation of endochondral bone formation. Mice in which the Spry2 gene has been deleted have defective chondrogenesis and endochondral bone formation, with a postnatal decrease in skeletal size and trabecular bone mass. In these constitutive Spry2 mutants, both chondrocytes and osteoblasts undergo increased cell proliferation and impaired terminal differentiation. Tissue-specific Spry2 deletion by either osteoblast- (Col1-Cre) or chondrocyte- (Col2-Cre) specific drivers led to decreased relative bone mass, demonstrating the critical role of Spry2 in both cell types. Molecular analyses of signaling pathways in Spry2−/− mice revealed an unexpected upregulation of BMP signaling and decrease in RTK signaling. These results identify Spry2 as a critical regulator of endochondral bone formation that modulates signaling in both osteoblast and chondrocyte lineages. PMID:27130872

  5. Developing Critical Thinking in E-Learning Environment: Kuwait University as a Case Study

    ERIC Educational Resources Information Center

    Al-Fadhli, Salah; Khalfan, Abdulwahed

    2009-01-01

    This article investigated the impact of using e-learning models' with the principles of constructivism to enhance the critical thinking skills of students in higher education institutions. The study examines the effectiveness of e-learning model in enhancing critical thinking of students at university level. This effectiveness is measured by a…

  6. A Rutile Chevron Modulation in Delafossite-Like Ga 3–x In 3 Ti x O 9+x/2

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

    Rickert, Karl; Boullay, Philippe; Malo, Sylvie

    2016-05-02

    The structure solution of the modulated, delafossite-related, orthorhombic Ga 3–xIn 3Ti xO 9+x/2 for x = 1.5 is reported here in conjunction with a model describing the modulation as a function of x for the entire system. Previously reported structures in the related A 3–xIn 3Ti xO 9+x/2 (A = Al, Cr, or Fe) systems use X-ray diffraction to determine that the anion lattice is the source of modulation. Neutron diffraction, with its enhanced sensitivity to light atoms, offers a route to solving the modulation and is used here, in combination with precession electron diffraction tomography (PEDT), to solve themore » structure of Ga 1.5In 3Ti 1.5O 9.75. We construct a model that describes the anion modulation through the formation of rutile chevrons as a function of x. This model accommodates the orthorhombic phase (1.5 ≤ x ≤ 2.1) in the Ga 3-xIn 3Ti xO 9+x/2 system, which transitions to a biphasic mixture (2.2 ≤ x ≤ 2.3) with a monoclinic, delafossite-related phase (2.4 ≤ x ≤ 2.5). The optical band gaps of this system are determined, and are stable at ~3.4 eV before a ~0.4 eV decrease between x = 1.9 and 2.0. After this decrease, stability resumes at ~3.0 eV. Resistance to oxidation and reduction is also presented.« less

  7. Doubling immunochemistry laboratory testing efficiency with the cobas e 801 module while maintaining consistency in analytical performance.

    PubMed

    Findeisen, P; Zahn, I; Fiedler, G M; Leichtle, A B; Wang, S; Soria, G; Johnson, P; Henzell, J; Hegel, J K; Bendavid, C; Collet, N; McGovern, M; Klopprogge, K

    2018-06-04

    The new immunochemistry cobas e 801 module (Roche Diagnostics) was developed to meet increasing demands on routine laboratories to further improve testing efficiency, while maintaining high quality and reliable data. During a non-interventional multicenter evaluation study, the overall performance, functionality and reliability of the new module was investigated under routine-like conditions. It was tested as a dedicated immunochemistry system at four sites and as a consolidator combined with clinical chemistry at three sites. We report on testing efficiency and analytical performance of the new module. Evaluation of sample workloads with site-specific routine request patterns demonstrated increased speed and almost doubled throughput (maximal 300 tests per h), thus revealing that one cobas e 801 module can replace two cobas e 602 modules while saving up to 44% floor space. Result stability was demonstrated by QC analysis per assay throughout the study. Precision testing over 21 days yielded excellent results within and between labs, and, method comparison performed versus the cobas e 602 module routine results showed high consistency of results for all assays under study. In a practicability assessment related to performance and handling, 99% of graded features met (44%) or even exceeded (55%) laboratory expectations, with enhanced reagent management and loading during operation being highlighted. By nearly doubling immunochemistry testing efficiency on the same footprint as a cobas e 602 module, the new module has a great potential to further consolidate and enhance laboratory testing while maintaining high quality analytical performance with Roche platforms. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. Dental students' evaluation of 2 community-oriented PBL modules.

    PubMed

    Pau, A K; Collinson, S; Croucher, R

    1999-11-01

    To evaluate dental students' perception of 2 problem-based learning (PBL) modules in Dental Public Health implemented within the context of a traditional formal curriculum. 2 dental community modules were implemented with an 8-month interval between them on the same group of dental undergraduates; the first in Term 2 and the second in Term 4 of a 5-year 15-term dental course. At the end of each module, a semi-structured questionnaire was administered to evaluate the introductory lecture, the fieldwork activity and the organisation of the modules. In both modules, students reported gaining insight into the subject matter, skills in teamwork, making presentations and collecting data. Some students in the 1st module needed more time to fulfil their learning objectives and had difficulty in collecting data. In the 2nd module, students reported that they lacked motivation because of the place of the module within their timetable. Opinions differed about groupwork. The content of and interest generated by fieldwork activity was rated more positively in the 2nd module than the 1st. Less positively rated in the 2nd module was the introductory lecture and module organisation. Implementing PBL within a traditional curriculum does not offer uniform outcomes for students. Optimum group size and adequate time are necessary if students are to benefit from PBL. A consistent and continuous PBL approach should be adopted rather than a sporadic one. Further research should establish the optimum balance between PBL and traditional approaches that would allow students to maximise the benefits of both and to identify those students best equipped to benefit from a 'mixed economy' of learning.

  9. First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum

    PubMed Central

    2011-01-01

    Background Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP. Results WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector. Conclusions The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1. PMID:21955916

  10. Adaptation and Evaluation of Online Self-learning Modules to Teach Critical Appraisal and Evidence-Based Practice in Nursing: An International Collaboration.

    PubMed

    Gagnon, Johanne; Gagnon, Marie-Pierre; Buteau, Rose-Anne; Azizah, Ginette Mbourou; Jetté, Sylvie; Lampron, Amélie; Simonyan, David; Asua, José; Reviriego, Eva

    2015-07-01

    Healthcare professionals need to update their knowledge and acquire skills to continually inform their practice based on scientific evidence. This study was designed to evaluate online self-learning modules on critical appraisal skills to promote the use of research in clinical practice among nurses from Quebec (Canada) and the Basque Country (Spain). The teaching material was developed in Quebec and adapted to the Basque Country as part of an international collaboration project. A prospective pre-post study was conducted with 36 nurses from Quebec and 47 from the Basque Country. Assessment comprised the administration of questionnaires before and after the course in order to explore the main intervention outcomes: knowledge acquisition and self-learning readiness. Satisfaction was also measured at the end of the course. Two of the three research hypotheses were confirmed: (1) participants significantly improved their overall knowledge score after the educational intervention; and (2) they were, in general, satisfied with the course, giving it a rating of seven out of 10. Participants also reported a greater readiness for self-directed learning after the course, but this result was not significant in Quebec. The study provides unique knowledge on the cultural adaptation of online self-learning modules for teaching nurses about critical appraisal skills and evidence-based practice.

  11. Serotonergic and peptidergic modulation of the buccal mass protractor muscle (I2) in aplysia.

    PubMed

    Hurwitz, I; Cropper, E C; Vilim, F S; Alexeeva, V; Susswein, A J; Kupfermann, I; Weiss, K R

    2000-12-01

    Plasticity of Aplysia feeding has largely been measured by noting changes in radula protraction. On the basis of previous work, it has been suggested that peripheral modulation may contribute to behavioral plasticity. However, peripheral plasticity has not been demonstrated in the neuromuscular systems that participate in radula protraction. Therefore in this study we investigated whether contractions of a major radula protraction muscle (I2) are subject to modulation. We demonstrate, first, that an increase in the firing frequency of the cholinergic I2 motoneurons will increase the amplitude of the resulting muscle contraction but will not modulate its relaxation rate. We show, second, that neuronal processes on the I2 muscle are immunoreactive to myomodulin (MM), RFamide, and serotonin (5-HT), but not to small cardioactive peptide (SCP) or buccalin. The I2 motoneurons B31, B32, B61, and B62 are not immunoreactive to RFamide, 5-HT, SCP, or buccalin. However, all four cells are MM immunoreactive and are capable of synthesizing MMa. Third, we show that the bioactivity of the different modulators is somewhat different; while the MMs (i.e., MMa and MMb) and 5-HT increase I2 muscle relaxation rate, and potentiate muscle contraction amplitude, MMa, at high concentrations, depresses muscle contractions. Fourth, our data suggest that cAMP at least partially mediates effects of modulators on contraction amplitude and relaxation rate.

  12. Developing Learning Model P3E to Improve Students’ Critical Thinking Skills of Islamic Senior High School

    NASA Astrophysics Data System (ADS)

    Bahtiar; Rahayu, Y. S.; Wasis

    2018-01-01

    This research aims to produce P3E learning model to improve students’ critical thinking skills. The developed model is named P3E, consisting of 4 (four) stages namely; organization, inquiry, presentation, and evaluation. This development research refers to the development stage by Kemp. The design of the wide scale try-out used pretest-posttest group design. The wide scale try-out was conducted in grade X of 2016/2017 academic year. The analysis of the results of this development research inludes three aspects, namely: validity, practicality, and effectiveness of the model developed. The research results showed; (1) the P3E learning model was valid, according to experts with an average value of 3.7; (2) The completion of the syntax of the learning model developed obtained 98.09% and 94.39% for two schools based on the assessment of the observers. This shows that the developed model is practical to be implemented; (3) the developed model is effective for improving students’ critical thinking skills, although the n-gain of the students’ critical thinking skills was 0.54 with moderate category. Based on the results of the research above, it can be concluded that the developed P3E learning model is suitable to be used to improve students’ critical thinking skills.

  13. Advanced Sine Wave Modulation of Continuous Wave Laser System for Atmospheric CO2 Differential Absorption Measurements

    NASA Technical Reports Server (NTRS)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.

    2014-01-01

    NASA Langley Research Center in collaboration with ITT Exelis have been experimenting with Continuous Wave (CW) laser absorption spectrometer (LAS) as a means of performing atmospheric CO2 column measurements from space to support the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission.Because range resolving Intensity Modulated (IM) CW lidar techniques presented here rely on matched filter correlations, autocorrelation properties without side lobes or other artifacts are highly desirable since the autocorrelation function is critical for the measurements of lidar return powers, laser path lengths, and CO2 column amounts. In this paper modulation techniques are investigated that improve autocorrelation properties. The modulation techniques investigated in this paper include sine waves modulated by maximum length (ML) sequences in various hardware configurations. A CW lidar system using sine waves modulated by ML pseudo random noise codes is described, which uses a time shifting approach to separate channels and make multiple, simultaneous online/offline differential absorption measurements. Unlike the pure ML sequence, this technique is useful in hardware that is band pass filtered as the IM sine wave carrier shifts the main power band. Both amplitude and Phase Shift Keying (PSK) modulated IM carriers are investigated that exibit perfect autocorrelation properties down to one cycle per code bit. In addition, a method is presented to bandwidth limit the ML sequence based on a Gaussian filter implemented in terms of Jacobi theta functions that does not seriously degrade the resolution or introduce side lobes as a means of reducing aliasing and IM carrier bandwidth.

  14. Comparative effectiveness of a serious game and an e-module to support patient safety knowledge and awareness.

    PubMed

    Dankbaar, Mary E W; Richters, Olivier; Kalkman, Cor J; Prins, Gerrie; Ten Cate, Olle T J; van Merrienboer, Jeroen J G; Schuit, Stephanie C E

    2017-02-02

    Serious games have the potential to teach complex cognitive skills in an engaging way, at relatively low costs. Their flexibility in use and scalability makes them an attractive learning tool, but more research is needed on the effectiveness of serious games compared to more traditional formats such e-modules. We investigated whether undergraduate medical students developed better knowledge and awareness and were more motivated after learning about patient-safety through a serious game than peers who studied the same topics using an e-module. Fourth-year medical students were randomly assigned to either a serious game that included video-lectures, biofeedback exercises and patient missions (n = 32) or an e-module, that included text-based lectures on the same topics (n = 34). A third group acted as a historical control-group without extra education (n = 37). After the intervention, which took place during the clinical introduction course, before the start of the first rotation, all students completed a knowledge test, a self-efficacy test and a motivation questionnaire. During the following 10-week clinical rotation they filled out weekly questionnaires on patient-safety awareness and stress. The results showed patient safety knowledge had equally improved in the game group and e-module group compared to controls, who received no extra education. Average learning-time was 3 h for the game and 1 h for the e-module-group. The serious game was evaluated as more engaging; the e-module as more easy to use. During rotations, students in the three groups reported low and similar levels of patient-safety awareness and stress. Students who had treated patients successfully during game missions experienced higher self-efficacy and less stress during their rotation than students who treated patients unsuccessfully. Video-lectures (in a game) and text-based lectures (in an e-module) can be equally effective in developing knowledge on specific topics. Although

  15. Advanced Intensity-Modulation Continuous-Wave Lidar Techniques for Column CO2 Measurements

    NASA Astrophysics Data System (ADS)

    Campbell, J. F.; Lin, B.; Obland, M. D.; Liu, Z.; Kooi, S. A.; Fan, T. F.; Nehrir, A. R.; Meadows, B.; Browell, E. V.

    2016-12-01

    Advanced Intensity-Modulation Continuous-Wave Lidar Techniques for Column CO2 MeasurementsJoel F. Campbell1, Bing Lin1, Michael D. Obland1, Zhaoyan Liu1, Susan Kooi2, Tai-Fang Fan2, Amin R. Nehrir1, Byron Meadows1, Edward V. Browell31NASA Langley Research Center, Hampton, VA 23681 2SSAI, NASA Langley Research Center, Hampton, VA 23681 3STARSS-II Affiliate, NASA Langley Research Center, Hampton, VA 23681 AbstractGlobal and regional atmospheric carbon dioxide (CO2) measurements for the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) space mission and the Atmospheric Carbon and Transport (ACT) - America project are critical for improving our understanding of global CO2 sources and sinks. Advanced Intensity-Modulated Continuous-Wave (IM-CW) lidar techniques are investigated as a means of facilitating CO2 measurements from space and airborne platforms to meet the ASCENDS and ACT-America science measurement requirements. In recent numerical, laboratory and flight experiments we have successfully used the Binary Phase Shift Keying (BPSK) modulation technique to uniquely discriminate surface lidar returns from intermediate aerosol and cloud returns. We demonstrate the utility of BPSK to eliminate sidelobes in the range profile as a means of making Integrated Path Differential Absorption (IPDA) column CO2 measurements in the presence of optically thin clouds, thereby minimizing bias errors caused by the clouds. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate cloud layers, which is a requirement for the inversion of column CO2 number density measurements to column CO2 mixing ratios, has been demonstrated using new sub-meter hyperfine interpolation techniques that takes advantage of the periodicity of the modulation waveforms. The BPSK technique under investigation has excellent auto-correlation properties while possessing a finite bandwidth. These techniques are used in a new data processing

  16. G2 Flywheel Module Design

    NASA Technical Reports Server (NTRS)

    Jensen, Ralph H.; Dever, Timothy P.

    2006-01-01

    Design of a flywheel module, designated the G2 module, is described. The G2 flywheel is a 60,000 RPM, 525 W-hr, 1 kW system designed for a laboratory environment; it will be used for component testing and system demonstrations, with the goal of applying flywheels to aerospace energy storage and integrated power and attitude control (IPACS) applications. G2 has a modular design, which allows for new motors, magnetic bearings, touchdown bearings, and rotors to be installed without a complete redesign of the system. This design process involves several engineering disciplines, and requirements are developed for the speed, energy storage, power level, and operating environment. The G2 rotor system consists of a multilayer carbon fiber rim with a titanium hub on which the other components mount, and rotordynamics analysis is conducted to ensure rigid and flexible rotor modes are controllable or outside of the operating speed range. Magnetic bearings are sized using 1-D magnetic circuit analysis and refined using 3-D finite element analysis. The G2 magnetic bearing system was designed by Texas A&M and has redundancy which allows derated operation after the loss of some components, and an existing liquid cooled two pole permanent magnet motor/generator is used. The touchdown bearing system is designed with a squeeze film damper system allowing spin down from full operating speed in case of a magnetic bearing failure. The G2 flywheel will enable module level demonstrations of component technology, and will be a key building block in system level attitude control and IPACS demonstrations.

  17. Whitham modulation theory for (2  +  1)-dimensional equations of Kadomtsev–Petviashvili type

    NASA Astrophysics Data System (ADS)

    Ablowitz, Mark J.; Biondini, Gino; Rumanov, Igor

    2018-05-01

    Whitham modulation theory for certain two-dimensional evolution equations of Kadomtsev–Petviashvili (KP) type is presented. Three specific examples are considered in detail: the KP equation, the two-dimensional Benjamin–Ono (2DBO) equation and a modified KP (m2KP) equation. A unified derivation is also provided. In the case of the m2KP equation, the corresponding Whitham modulation system exhibits features different from the other two. The approach presented here does not require integrability of the original evolution equation. Indeed, while the KP equation is known to be a completely integrable equation, the 2DBO equation and the m2KP equation are not known to be integrable. In each of the cases considered, the Whitham modulation system obtained consists of five first-order quasilinear partial differential equations. The Riemann problem (i.e. the analogue of the Gurevich–Pitaevskii problem) for the one-dimensional reduction of the m2KP equation is studied. For the m2KP equation, the system of modulation equations is used to analyze the linear stability of traveling wave solutions.

  18. Long-term modulation of mitochondrial Ca2+ signals by protein kinase C isozymes

    PubMed Central

    Pinton, Paolo; Leo, Sara; Wieckowski, Mariusz R.; Di Benedetto, Giulietta; Rizzuto, Rosario

    2004-01-01

    The modulation of Ca2+ signaling patterns during repetitive stimulations represents an important mechanism for integrating through time the inputs received by a cell. By either overexpressing the isoforms of protein kinase C (PKC) or inhibiting them with specific blockers, we investigated the role of this family of proteins in regulating the dynamic interplay of the intracellular Ca2+ pools. The effects of the different isoforms spanned from the reduction of ER Ca2+ release (PKCα) to the increase or reduction of mitochondrial Ca2+ uptake (PKCζ and PKCβ/PKCδ, respectively). This PKC-dependent regulatory mechanism underlies the process of mitochondrial Ca2+ desensitization, which in turn modulates cellular responses (e.g., insulin secretion). These results demonstrate that organelle Ca2+ homeostasis (and in particular mitochondrial processing of Ca2+ signals) is tuned through the wide molecular repertoire of intracellular Ca2+ transducers. PMID:15096525

  19. Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

    PubMed Central

    Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

    2009-01-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site of action of PGE2 in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n=6) on days 11-12 of the estrous cycle were treated with vehicle (control), PGE2 (100 nM), E2 (1-100 nM) or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1 and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1 and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Co-treatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium, and was significantly up-regulated on days 11-12 of pregnancy. Our results suggest that E2, prevents luteolysis through enzymatic modification of PG synthesis and that E2, PGE2 and endometrial PTGER2 are involved in PGE2 positive feedback loop in porcine endometrium. PMID:19359378

  20. Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

    PubMed Central

    Fraunberger, Erik A.; Laliberté, Victoria L. M.; Duong, Angela; Andreazza, Ana C.

    2016-01-01

    Although antioxidants, redox modulations, and neuropsychiatric disorders have been widely studied for many years, the field would benefit from an integrative and corroborative review. Our primary objective is to delineate the biological significance of compounds that modulate our redox status (i.e., reactive species and antioxidants) as well as outline their current role in brain health and the impact of redox modulations on the severity of illnesses. Therefore, this review will not enter into the debate regarding the perceived medical legitimacy of antioxidants but rather seek to clarify their abilities and limitations. With this in mind, antioxidants may be interpreted as natural products with significant pharmacological actions in the body. A renewed understanding of these often overlooked compounds will allow us to critically appraise the current literature and provide an informed, novel perspective on an important healthcare issue. In this review, we will introduce the complex topics of redox modulations and their role in the development of select neuropsychiatric disorders. PMID:26640614

  1. Estrogen's Place in the Family of Synaptic Modulators.

    PubMed

    Kramár, Enikö A; Chen, Lulu Y; Rex, Christopher S; Gall, Christine M; Lynch, Gary

    2009-01-01

    Estrogen, in addition to its genomic effects, triggers rapid synaptic changes in hippocampus and cortex. Here we summarize evidence that the acute actions of the steroid arise from actin signaling cascades centrally involved in long-term potentiation (LTP). A 10-min infusion of E2 reversibly increased fast EPSPs and promoted theta burst-induced LTP within adult hippocampal slices. The latter effect reflected a lowered threshold and an elevated ceiling for the potentiation effect. E2's actions on transmission and plasticity were completely blocked by latrunculin, a toxin that prevents actin polymerization. E2 also caused a reversible increase in spine concentrations of filamentous (F-) actin and markedly enhanced polymerization caused by theta burst stimulation (TBS). Estrogen activated the small GTPase RhoA, but not the related GTPase Rac, and phosphorylated (inactivated) synaptic cofilin, an actin severing protein targeted by RhoA. An inhibitor of RhoA kinase (ROCK) thoroughly suppressed the synaptic effects of E2. Collectively, these results indicate that E2 engages a RhoA >ROCK> cofilin> actin pathway also used by brain-derived neurotrophic factor and adenosine, and therefore belongs to a family of 'synaptic modulators' that regulate plasticity. Finally, we describe evidence that the acute signaling cascade is critical to the depression of LTP produced by ovariectomy.

  2. Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways.

    PubMed

    Bezerra, Fábio; Ferreira, Marcel R; Fontes, Giselle N; da Costa Fernandes, Célio Jr; Andia, Denise C; Cruz, Nilson C; da Silva, Rodrigo A; Zambuzzi, Willian F

    2017-08-01

    Although, intracellular signaling pathways are proposed to predict the quality of cell-surface relationship, this study addressed pre-osteoblast behavior in response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring critical intracellular pathways and pre-osteoblast morphological change. Physicochemical properties were evaluated by atomic force microscopy (AFM) and wettability considering water contact angle of three differently texturized Ti surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite-blasted (nHA). The results revealed critical differences in surface topography, impacting the water contact angle and later the osteoblast performance. In order to evaluate the effect of those topographical characteristics on biological responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and subjected the cultures to biological analysis. First, we have observed pre-osteoblasts morphological changes resulting from the interaction with the Ti texturized surfaces whereas the cells cultured on nHA presented a more advanced spreading process when compared with the cells cultured on the other surfaces. These results argued us for analyzing the molecular machinery and thus, we have shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti-apoptotic effect, maybe explained by the fact that HA is a natural element present in bone composition. Thereafter, we investigated the potential effect of those surfaces on promoting pre-osteoblast adhesion and survival signaling by performing crystal violet and immunoblotting approaches, respectively. Our results showed that nHA promoted a higher pre-osteoblast adhesion supported by up-modulating FAK and Src activations, both signaling transducers involved during eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able to promote osteoblast differentiation

  3. Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation

    PubMed Central

    Lechtenberg, Bernhard C.; Rajput, Akhil; Sanishvili, Ruslan; Dobaczewska, Małgorzata K.; Ware, Carl F.; Mace, Peter D.; Riedl, Stefan J.

    2015-01-01

    Ubiquitination is a central process affecting all facets of cellular signaling and function1. A critical step in ubiquitination is the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate or a growing ubiquitin chain, which is mediated by E3 ubiquitin ligases. RING-type E3 ligases typically facilitate the transfer of ubiquitin from the E2 directly to the substrate2,3. The RBR family of RING-type E3 ligases, however, breaks this paradigm by forming a covalent intermediate with ubiquitin similarly to HECT-type E3 ligases4–6. The RBR family includes Parkin4 and HOIP, the central catalytic factor of the linear ubiquitin chain assembly complex (LUBAC)7. While structural insights into the RBR E3 ligases Parkin and HHARI in their overall autoinhibited forms are available8–13, no structures exist of intact fully active RBR E3 ligases or any of their complexes. Thus, the RBR mechanism of action has remained largely enigmatic. Here we present the first structure of the fully active HOIP-RBR in its transfer complex with an E2~ubiquitin conjugate, which elucidates the intricate nature of RBR E3 ligases. The active HOIP-RBR adopts a conformation markedly different from that of autoinhibited RBRs. HOIP-RBR binds the E2~ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centers ideally aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. In addition, surprisingly, three distinct helix–IBR-fold motifs inherent to RBRs form ubiquitin-binding regions that engage the activated ubiquitin of the E2~Ub conjugate as well as an additional regulatory ubiquitin molecule. The features uncovered reveal critical states of the HOIP-RBR E3 ligase cycle, and comparison with Parkin and HHARI suggests a general mechanism for RBR E3 ligases. PMID:26789245

  4. Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy.

    PubMed

    Joshi, Gururaj; Gan, Kok Ann; Johnson, Delinda A; Johnson, Jeffrey A

    2015-02-01

    The presence of senile plaques is one of the major pathologic hallmarks of the brain with Alzheimer's disease (AD). The plaques predominantly contain insoluble amyloid β-peptide, a cleavage product of the larger amyloid precursor protein (APP). Two enzymes, named β and γ secretase, generate the neurotoxic amyloid-β peptide from APP. Mature APP is also turned over endogenously by autophagy, more specifically by the endosomal-lysosomal pathway. A defective lysosomal system is known to be pathogenic in AD. Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders, and Nrf2 has become a potential therapeutic target for various neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. In the current study, we explored the effect of genetic ablation of Nrf2 on APP/Aβ processing and/or aggregation as well as changes in autophagic dysfunction in APP/PS1 mice. There was a significant increase in inflammatory response in APP/PS1 mice lacking Nrf2. This was accompanied by increased intracellular levels of APP, Aβ (1-42), and Aβ (1-40), without a change total full-length APP. There was a shift of APP and Aβ into the insoluble fraction, as well as increased poly-ubiquitin conjugated proteins in mice lacking Nrf2. APP/PS1-mediated autophagic dysfunction is also enhanced in Nrf2-deficient mice. Finally, neurons in the APP/PS1/Nrf2-/- mice had increased accumulation of multivesicular bodies, endosomes, and lysosomes. These outcomes provide a better understanding of the role of Nrf2 in modulating autophagy in an AD mouse model and may help design better Nrf2 targeted therapeutics that could be efficacious in the treatment of AD. Published by Elsevier Inc.

  5. Analysis of critical thinking ability of VII grade students based on the mathematical anxiety level through learning cycle 7E model

    NASA Astrophysics Data System (ADS)

    Widyaningsih, E.; Waluya, S. B.; Kurniasih, A. W.

    2018-03-01

    This study aims to know mastery learning of students’ critical thinking ability with learning cycle 7E, determine whether the critical thinking ability of the students with learning cycle 7E is better than students’ critical thinking ability with expository model, and describe the students’ critical thinking phases based on the mathematical anxiety level. The method is mixed method with concurrent embedded. The population is VII grade students of SMP Negeri 3 Kebumen academic year 2016/2017. Subjects are determined by purposive sampling, selected two students from each level of mathematical anxiety. Data collection techniques include test, questionnaire, interview, and documentation. Quantitative data analysis techniques include mean test, proportion test, difference test of two means, difference test of two proportions and for qualitative data used Miles and Huberman model. The results show that: (1) students’ critical thinking ability with learning cycle 7E achieve mastery learning; (2) students’ critical thinking ability with learning cycle 7E is better than students’ critical thinking ability with expository model; (3) description of students’ critical thinking phases based on the mathematical anxiety level that is the lower the mathematical anxiety level, the subjects have been able to fulfil all of the indicators of clarification, assessment, inference, and strategies phases.

  6. Rescue Manual. Module 2.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The second of 10 modules contains 5 chapters: (1) patient care and handling techniques; (2) rescue carries and drags; (3) emergency vehicle operations; (4) self-contained breathing apparatus; and (5) protective clothing. Key points, an…

  7. A comparative evaluation of rate of space closure after extraction using E-chain and stretched modules in bimaxillary dentoalveolar protrusion cases.

    PubMed

    Mitra, Rajat; Londhe, S M; Kumar, Prasanna

    2011-04-01

    Aim of this study was to compare the rate of space closure between E-chain mechanics in one side of upper arch and by elastomeric module with ligature wire on the contralateral side in same patient. Thirty bimaxillary dentoalveolar protrusion cases were taken up for comprehensive fixed orthodontic treatment after extraction of all first premolars to retract both upper and lower anterior teeth. After initial alignment and levelling, alginate impressions were made for upper and lower arches and models constructed. In the upper arch model a vernier caliper was used to measure the extraction space in both sides from middle point of distal surface of canine to the middle most point of mesial surface of second premolar. This is the amount of space present before the onset of retraction mechanics. During space closure procedure two different retracting components were applied in right and left sides of each case. On right side elastic chain (E-chain) applied in both upper and lower arches and on left side elastomeric module with steel ligature (0.010") stretched double its diameter fixed in both arches. Both the mechanisms produced approximately 250-300 g of force as measured by a tension gauge. After onset of retraction mechanism all patients were recalled after every six weeks for three visits. In all these three visits modules and E-chains were changed. In all three visits impression was made, models constructed, and the remaining available space was measured by a vernier caliper up to 0.1 mm level variations. Mean value for total space closure in case of E-chain was 2.777 mm whereas in case of module with ligature wire the value increased to 3.017 mm. Mean value for rate of space closure in case of E-chain was 0.2143 mm, whereas in case of module with ligature wire the value increased to 0.2343 mm with a standard deviation of 0.001104 and 0.001194, respectively. The standard deviation for total space closure was 0.1305 for E-chain and 0.1487 for module with ligature

  8. A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer.

    PubMed

    Yang, Mary Qu; Li, Dan; Yang, William; Zhang, Yifan; Liu, Jun; Tong, Weida

    2017-01-01

    Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1 , as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways.

  9. Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

    PubMed

    Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

    2015-09-05

    Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. The development of form two mathematics i-Think module (Mi-T2)

    NASA Astrophysics Data System (ADS)

    Yao, Foo Jing; Abdullah, Mohd Faizal Nizam Lee; Tien, Lee Tien

    2017-05-01

    This study aims to develop a training module i-THINK Mathematics Form Two (Mi-T2) to increase the higher-order thinking skills of students. The Mi-T2 training module was built based on the Sidek Module Development Model (2001). Constructivist learning theory, cognitive learning theory, i-THINK map and higher order thinking skills were the building blocks of the module development. In this study, researcher determined the validity and reliability of Mi-T2 module. The design being used in this study was descriptive study. To determine the needs of Mi-T2 module, questionnaires and literature review were used to collect data. When the need of the module was determined, the module was built and a pilot study was conducted to test the reliability of the Mi-T2 module. The pilot study was conducted at a secondary school in North Kinta, Perak. A Form Two class was selected to be the sample study through clustered random sampling. The pilot study was conducted for two months and one topic had been studied. The Mi-T2 module was evaluated by five expert panels to determine the content validity of the module. The instruments being used in the study were questionnaires about the necessity of the Mi-T2 module for guidance, questionnaires about the validity of the module and questionnaires concerning the reliability of the module. Statistical analysis was conducted to determine the validity and reliability coefficients of the Mi-T2 module. The content validity of Mi-T2 module was determined by Cohen's Kappa's (1968) agreement coefficient and the reliability of Mi-T2 module was determined by Cronbach Alpha's value scale. The content validity of Mi-T2 module was 0.89 and the Cronbach Alpha's value of Mi-T2 module was 0.911.

  11. PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth

    PubMed Central

    Gruzdev, Artiom; Nguyen, MyTrang; Kovarova, Martina; Koller, Beverly H.

    2012-01-01

    The ductus arteriosus (DA) is a fetal shunt that directs right ventricular outflow away from pulmonary circulation and into the aorta. Critical roles for prostaglandin E2 (PGE2) and the EP4 receptor (EP4) have been established in maintaining both the patency of the vessel in utero and in its closure at birth. Here we have generated mice in which loss of EP4 expression is limited to either the smooth muscle (SMC) or endothelial cells and demonstrated that SMC, but not endothelial cell expression of EP4 is required for DA closure. The genome wide expression analysis of full term wild type and EP4−/− DA indicates that PGE2/EP4 signaling modulates expression of a number of unique pathways, including those involved in SMC proliferation, cell migration, and vascular tone. Together this supports a mechanism by which maturation and increased contractility of the vessel is coupled to the potent smooth muscle dilatory actions of PGE2. PMID:22342504

  12. Amygdala NRG1–ErbB4 Is Critical for the Modulation of Anxiety-Like Behaviors

    PubMed Central

    Bi, Lin-Lin; Sun, Xiang-Dong; Zhang, Jie; Lu, Yi-Sheng; Chen, Yi-Hua; Wang, Jue; Geng, Fei; Liu, Fang; Zhang, Meng; Liu, Ji-Hong; Li, Xiao-Wen; Mei, Lin; Gao, Tian-Ming

    2015-01-01

    Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1–ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1–ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia. PMID:25308353

  13. An E-learning Module on Chronic Low Back Pain in Older Adults: Effect on Medical Resident Attitudes, Confidence, Knowledge, and Clinical Skills.

    PubMed

    Jacobs, Zachary G; Elnicki, D Michael; Perera, Subashan; Weiner, Debra K

    2018-01-05

    To determine 1) the feasibility of implementing an e-learning module on chronic low back pain (CLBP) in an older adult into an existing internal medicine residency curriculum and 2) the impact of this module on resident attitudes, confidence, knowledge, and clinical skills relating to CLBP. Participants were assigned to complete either the online module (N = 73) or the Yale Office-based curriculum on CLBP (N = 70). Attitudes, confidence, and knowledge were evaluated pre- and postintervention via survey. A retrospective blinded chart review of resident clinic encounters was conducted, wherein diagnosis codes and physical exam documentation were rated as basic or advanced. There was no improvement in overall knowledge scores in either group (60% average on both metrics). There were tendencies for greater improvements in the intervention group compared with controls for confidence in managing fibromyalgia (2.4 to 2.9 vs 2.5 to 2.5, P = 0.06) and leg length discrepancy (1.8 to 2.5 vs 1.5 to 1.9, P = 0.05). Those exposed to the online module also showed an increase in the percentage of physical exam documentation rated as advanced following the intervention (13% to 32%, P = 0.006), whereas the control group showed no change (14% to 12%, P = 0.68). An online module on CLBP in the older adult was a feasible addition to an existing curriculum for internal medicine residents. The module positively and substantively impacted resident clinical behaviors, as evidenced by enhanced sophistication in physical exam documentation; it also was associated with improved confidence in certain aspects of chronic pain management. © 2018 American Academy of Pain Medicine. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  14. Mu2e transport solenoid prototype tests results

    DOE PAGES

    Lopes, Mauricio L.; G. Ambrosio; DiMarco, J.; ...

    2016-02-08

    The Fermilab Mu2e experiment has been developed to search for evidence of charged lepton flavor violation through the direct conversion of muons into electrons. The transport solenoid is an s-shaped magnet which guides the muons from the source to the stopping target. It consists of fifty-two superconducting coils arranged in twenty-seven coil modules. A full-size prototype coil module, with all the features of a typical module of the full assembly, was successfully manufactured by a collaboration between INFN-Genoa and Fermilab. The prototype contains two coils that can be powered independently. In order to validate the design, the magnet went throughmore » an extensive test campaign. Warm tests included magnetic measurements with a vibrating stretched wire, electrical and dimensional checks. As a result, the cold performance was evaluated by a series of power tests as well as temperature dependence and minimum quench energy studies.« less

  15. Middle School Engineering Problem Solving Using Traditional vs. e-PBL Module Instruction

    NASA Astrophysics Data System (ADS)

    Baele, Loren C.

    This multiple methods (Denzin, 1978) study investigated two instructional approaches, traditional module and electronic Problem-Based Learning instruction (e-PBL), used within a middle school engineering classroom focused on the variables of engagement, content knowledge, student self-assessment and teacher assessment of problem solving solutions. A non-equivalent group quasi-experimental research design (Creswell, 2015) was used on middle school students (N = 100) between those that received traditional module instruction (n = 51) and e-PBL instruction (n = 49). The qualitative approach of triangulation (Jick, 1979) was used to identify emergent themes for both between and within methods of data analysis on student engagement survey responses, two days of field observations notes, and six student interview transcripts. The quantitative results identified that students who received e-PBL instruction self-reported significantly greater engagement than those who received traditional module instruction. Further, there was a significant interaction effect between engineering content knowledge by group and gender as males who received e-PBL instruction had greater growth of content knowledge scores than males receiving traditional instruction, while females who received traditional instruction had greater growth of content knowledge scores than females in the e-PBL group. Through triangulation of the qualitative data, the emergent themes of the study suggest that hands-on learning produces higher levels of reported engagement independent of instructional method. The emergence of problem solving fatigue developed when both study groups reported a decline in engagement when entering into the final phase of the quantitative study suggesting that too many complex, ill-structured problems in rapid succession may negatively impact student engagement. Although females within the treatment group were most engaged, they did not achieve the knowledge growth of the females in the

  16. A fast and robust TOUGH2 module to simulate geological CO2 storage in saline aquifers

    NASA Astrophysics Data System (ADS)

    Shabani, Babak; Vilcáez, Javier

    2018-02-01

    A new TOUGH2 module to simulate geological CO2 storage (GCS) in saline aquifers is developed based on the widely employed ECO2N module of TOUGH2. The newly developed TOUGH2 module uses a new non-iterative fugacity-activity thermodynamic model to obtain the partitioning of CO2 and H2O between the aqueous and gas phases. Simple but robust thermophysical correlations are used to obtain density, viscosity, and enthalpy of the gas phase. The implementation and accuracy of the employed thermophysical correlations are verified by comparisons against the national institute of standards and technology (NIST) online thermophysical database. To assess the computation accuracy and efficiency, simulation results obtained with the new TOUGH2 module for a one-dimensional non-isothermal radial and a three-dimensional isothermal system are compared against the simulation results obtained with the ECO2N module. Treating salt mass fraction in the aqueous phase as a constant, along with the inclusion of a non-iterative fugacity-activity thermodynamic model, and simple thermophysical correlations, resulted in simulations much faster than simulations with ECO2N module, without losing numerical accuracy. Both modules yield virtually identical results. Additional field-scale simulations of CO2 injection into an actual non-isothermal and heterogeneous geological formation confirmed that the new module is much faster than the ECO2N module in simulating complex field-scale conditions. Owing to its capability to handle CO2-CH4-H2S-N2 gas mixtures and its compatibility with TOUGHREACT, this new TOUGH2 module offers the possibility of developing a fast and robust TOUGHREACT module to predict the fate of CO2 in GCS sites under biotic conditions where CO2, CH4, H2S, and N2 gases can be formed.

  17. E2E: A Summary of the e2e Learning Framework.

    ERIC Educational Resources Information Center

    Learning and Skills Development Agency, London (England).

    This publication is a summary of the E2E (Entry to Employment) Learning Framework that provides guidance on program implementation. (E2E is a new learning program for young people not yet ready or able to enter Modern Apprenticeship programs, a Level 2 program, or employment directly.) Section 2 highlights core values to which all involved should…

  18. Modulation-doped β-(Al0.2Ga0.8)2O3/Ga2O3 field-effect transistor

    NASA Astrophysics Data System (ADS)

    Krishnamoorthy, Sriram; Xia, Zhanbo; Joishi, Chandan; Zhang, Yuewei; McGlone, Joe; Johnson, Jared; Brenner, Mark; Arehart, Aaron R.; Hwang, Jinwoo; Lodha, Saurabh; Rajan, Siddharth

    2017-07-01

    Modulation-doped heterostructures are a key enabler for realizing high mobility and better scaling properties for high performance transistors. We report the realization of a modulation-doped two-dimensional electron gas (2DEG) at the β-(Al0.2Ga0.8)2O3/Ga2O3 heterojunction by silicon delta doping. The formation of a 2DEG was confirmed using capacitance voltage measurements. A modulation-doped 2DEG channel was used to realize a modulation-doped field-effect transistor. The demonstration of modulation doping in the β-(Al0.2Ga0.8)2O3/Ga2O3 material system could enable heterojunction devices for high performance electronics.

  19. A Comparison of Potential IM-CW Lidar Modulation Techniques for ASCENDS CO2 Column Measurements From Space

    NASA Technical Reports Server (NTRS)

    Campbell, Joel F.; Lin, Bing; Nehrir, Amin R.; Harrison, F. Wallace; Obland, Michael D.; Ismail, Syed

    2014-01-01

    Global atmospheric carbon dioxide (CO2) measurements through the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) Decadal Survey recommended space mission are critical for improving our understanding of CO2 sources and sinks. IM-CW (Intensity Modulated Continuous Wave) lidar techniques are investigated as a means of facilitating CO2 measurements from space to meet the ASCENDS science requirements. In previous laboratory and flight experiments we have successfully used linear swept frequency modulation to discriminate surface lidar returns from intermediate aerosol and cloud contamination. Furthermore, high accuracy and precision ranging to the surface as well as to the top of intermediate clouds, which is a requirement for the inversion of the CO2 column-mixing ratio from the instrument optical depth measurements, has been demonstrated with the linear swept frequency modulation technique. We are concurrently investigating advanced techniques to help improve the auto-correlation properties of the transmitted waveform implemented through physical hardware to make cloud rejection more robust in special restricted scenarios. Several different carrier based modulation techniques are compared including orthogonal linear swept, orthogonal non-linear swept, and Binary Phase Shift Keying (BPSK). Techniques are investigated that reduce or eliminate sidelobes. These techniques have excellent auto-correlation properties while possessing a finite bandwidth (by way of a new cyclic digital filter), which will reduce bias error in the presence of multiple scatterers. Our analyses show that the studied modulation techniques can increase the accuracy of CO2 column measurements from space. A comparison of various properties such as signal to noise ratio (SNR) and time-bandwidth product are discussed.

  20. An ELMO2-RhoG-ILK network modulates microtubule dynamics.

    PubMed

    Jackson, Bradley C; Ivanova, Iordanka A; Dagnino, Lina

    2015-07-15

    ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. © 2015 Jackson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    PubMed

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  2. Plumbing. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Brath, Ed

    These 26 Student Training Modules on plumbing comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 577.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  3. Plastering. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Hamblen, Ron

    These 20 Student Training Modules on plastering comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 569.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  4. Drywall. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Moore, Doug

    These 18 Student Training Modules on drywall comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 573.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  5. Tilesetting. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Ausland, Greg

    These 24 Student Training Modules on tilesetting comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 563.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  6. Bricklaying. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Cholewinski, Scott

    These 23 Student Training Modules on bricklaying comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 567.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  7. Painting. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Kracht, Shannon

    These 21 Student Training Modules on painting comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 561.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  8. BPM-CUL3 E3 ligase modulates thermotolerance by facilitating negative regulatory domain-mediated degradation of DREB2A in Arabidopsis.

    PubMed

    Morimoto, Kyoko; Ohama, Naohiko; Kidokoro, Satoshi; Mizoi, Junya; Takahashi, Fuminori; Todaka, Daisuke; Mogami, Junro; Sato, Hikaru; Qin, Feng; Kim, June-Sik; Fukao, Yoichiro; Fujiwara, Masayuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2017-10-03

    DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A (DREB2A) acts as a key transcription factor in both drought and heat stress tolerance in Arabidopsis and induces the expression of many drought- and heat stress-inducible genes. Although DREB2A expression itself is induced by stress, the posttranslational regulation of DREB2A, including protein stabilization, is required for its transcriptional activity. The deletion of a 30-aa central region of DREB2A known as the negative regulatory domain (NRD) transforms DREB2A into a stable and constitutively active form referred to as DREB2A CA. However, the molecular basis of this stabilization and activation has remained unknown for a decade. Here we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the Cullin3 (CUL3)-based E3 ligase, as DREB2A-interacting proteins. We observed that DREB2A and BPMs interact in the nuclei, and that the NRD of DREB2A is sufficient for its interaction with BPMs. BPM -knockdown plants exhibited increased DREB2A accumulation and induction of DREB2A target genes under heat and drought stress conditions. Genetic analysis indicated that the depletion of BPM expression conferred enhanced thermotolerance via DREB2A stabilization. Thus, the BPM-CUL3 E3 ligase is likely the long-sought factor responsible for NRD-dependent DREB2A degradation. Through the negative regulation of DREB2A stability, BPMs modulate the heat stress response and prevent an adverse effect of excess DREB2A on plant growth. Furthermore, we found the BPM recognition motif in various transcription factors, implying a general contribution of BPM-mediated proteolysis to divergent cellular responses via an accelerated turnover of transcription factors.

  9. BPM-CUL3 E3 ligase modulates thermotolerance by facilitating negative regulatory domain-mediated degradation of DREB2A in Arabidopsis

    PubMed Central

    Morimoto, Kyoko; Ohama, Naohiko; Kidokoro, Satoshi; Mizoi, Junya; Takahashi, Fuminori; Todaka, Daisuke; Mogami, Junro; Sato, Hikaru; Qin, Feng; Kim, June-Sik; Fukao, Yoichiro; Fujiwara, Masayuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2017-01-01

    DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A (DREB2A) acts as a key transcription factor in both drought and heat stress tolerance in Arabidopsis and induces the expression of many drought- and heat stress-inducible genes. Although DREB2A expression itself is induced by stress, the posttranslational regulation of DREB2A, including protein stabilization, is required for its transcriptional activity. The deletion of a 30-aa central region of DREB2A known as the negative regulatory domain (NRD) transforms DREB2A into a stable and constitutively active form referred to as DREB2A CA. However, the molecular basis of this stabilization and activation has remained unknown for a decade. Here we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the Cullin3 (CUL3)-based E3 ligase, as DREB2A-interacting proteins. We observed that DREB2A and BPMs interact in the nuclei, and that the NRD of DREB2A is sufficient for its interaction with BPMs. BPM-knockdown plants exhibited increased DREB2A accumulation and induction of DREB2A target genes under heat and drought stress conditions. Genetic analysis indicated that the depletion of BPM expression conferred enhanced thermotolerance via DREB2A stabilization. Thus, the BPM-CUL3 E3 ligase is likely the long-sought factor responsible for NRD-dependent DREB2A degradation. Through the negative regulation of DREB2A stability, BPMs modulate the heat stress response and prevent an adverse effect of excess DREB2A on plant growth. Furthermore, we found the BPM recognition motif in various transcription factors, implying a general contribution of BPM-mediated proteolysis to divergent cellular responses via an accelerated turnover of transcription factors. PMID:28923951

  10. Butyl paraben and propyl paraben modulate bisphenol A and estradiol concentrations in female and male mice

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

    Pollock, Tyler; Weaver, Rachel E.; Ghasemi, Ramtin

    People are routinely exposed to the antimicrobial preservatives butyl paraben (BP) and propyl paraben (PP), as well as the monomer of polycarbonate plastics, bisphenol A (BPA). These chemicals are reliably detected in human urine and potentially interact. We investigated whether BP or PP exposure can modulate the concentrations of {sup 14}C-BPA and 17β-estradiol (E{sub 2}). Female and male CF1 mice were each given a subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BP or PP, then given a dietary supplement containing 50 μg/kg {sup 14}C-BPA. Radioactivity was measured in tissues through liquid scintillation counting. Significantly elevatedmore » {sup 14}C-BPA concentrations were observed following BP treatment in blood serum of both sexes, as well as the lungs, uterus, and ovaries of females and the testes and epididymides of males. Treatment with PP significantly elevated {sup 14}C-BPA concentrations in the uterus only. In another experiment, female and male CF1 mice were each injected with vehicle, 3 mg BP, or 3 mg PP, and E{sub 2} was measured in urine 2–12 h later. Whereas PP did not affect E{sub 2}, BP significantly elevated E{sub 2} 6–10 h after injection in females and 8 h after injection in males. These data indicate that BP and PP can alter the pharmacokinetics of BPA in vivo, and that BP can modulate E{sub 2} concentrations. These results are consistent with evidence that parabens inhibit enzymes that are critical for BPA and E{sub 2} metabolism, and demonstrate the importance of considering concurrent exposure to multiple chemicals when determining regulatory exposure limits. - Highlights: • We studied whether paraben exposure affects the distribution of oral {sup 14}C-BPA. • Elevated {sup 14}C–BPA was observed in mice given butyl or propyl paraben. • We also studied whether paraben exposure affects natural E{sub 2} levels in urine. • Elevated E{sub 2} was observed in mice given butyl, but not propyl, paraben.

  11. Translational control of auditory imprinting and structural plasticity by eIF2α.

    PubMed

    Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

    2016-12-23

    The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders.

  12. Rescue Manual. Module 4.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The fourth of 10 modules contains 8 chapters: (1) construction and characteristics of rescue rope; (2) knots, bends, and hitches; (3) critical angles; (4) raising systems; (5) rigging; (6) using the brake-bar rack for rope rescue; (7) rope…

  13. Use of Live Interactive Webcasting for an International Postgraduate Module in eHealth: Case Study Evaluation

    PubMed Central

    Maramba, Inocencio; Boulos, Maged N Kamel; Alexander, Tara

    2009-01-01

    Background Producing “traditional” e-learning can be time consuming, and in a topic such as eHealth, it may have a short shelf-life. Students sometimes report feeling isolated and lacking in motivation. Synchronous methods can play an important part in any blended approach to learning. Objective The aim was to develop, deliver, and evaluate an international postgraduate module in eHealth using live interactive webcasting. Methods We developed a hybrid solution for live interactive webcasting using a scan converter, mixer, and digitizer, and video server to embed a presenter-controlled talking head or copy of the presenter’s computer screen (normally a PowerPoint slide) in a student chat room. We recruited 16 students from six countries and ran weekly 2.5-hour live sessions for 10 weeks. The content included the use of computers by patients, patient access to records, different forms of e-learning for patients and professionals, research methods in eHealth, geographic information systems, and telehealth. All sessions were recorded—presentations as video files and the student interaction as text files. Students were sent an email questionnaire of mostly open questions seeking their views of this form of learning. Responses were collated and anonymized by a colleague who was not part of the teaching team. Results Sessions were generally very interactive, with most students participating actively in breakout or full-class discussions. In a typical 2.5-hour session, students posted about 50 messages each. Two students did not complete all sessions; one withdrew from the pressure of work after session 6, and one from illness after session 7. Fourteen of the 16 responded to the feedback questionnaire. Most students (12/14) found the module useful or very useful, and all would recommend the module to others. All liked the method of delivery, in particular the interactivity, the variety of students, and the “closeness” of the group. Most (11/14) felt

  14. Modulation of ColE1-like Plasmid Replication for Recombinant Gene Expression

    PubMed Central

    Camps, Manel

    2010-01-01

    ColE1-like plasmids constitute the most popular vectors for recombinant protein expression. ColE1 plasmid replication is tightly controlled by an antisense RNA mechanism that is highly dynamic, tuning plasmid metabolic burden to the physiological state of the host. Plasmid homeostasis is upset upon induction of recombinant protein expression because of non-physiological levels of expression and because of the frequently biased amino acid composition of recombinant proteins. Disregulation of plasmid replication is the main cause of collapse of plasmid-based expression systems because of a simultaneous increase in the metabolic burden (due to increased average copy number) and in the probability of generation of plasmid-free cells (due to increased copy number variation). Interference between regulatory elements of co-resident plasmids causes comparable effects on plasmid stability (plasmid incompatibility). Modulating plasmid copy number for recombinant gene expression aims at achieving a high gene dosage while preserving the stability of the expression system. Here I present strategies targeting plasmid replication for optimizing recombinant gene expression. Specifically, I review approaches aimed at modulating the antisense regulatory system (as well as their implications for plasmid incompatibility) and innovative strategies involving modulation of host factors, of R-loop formation, and of the timing of recombinant gene expression. PMID:20218961

  15. Orion Crew Module Adapter

    NASA Image and Video Library

    2015-11-12

    Offloading of the Orion Crew Module Adapter, CMA, at Plum Brook Station. The adapter will connect Orion’s crew module to a service module provided by ESA (European Space Agency). NASA is preparing for a series of tests that will check out the Orion European Service Module, a critical part of the spacecraft that will be launched on future missions to an asteroid and on toward Mars.

  16. Amplitude modulation detection with concurrent frequency modulation.

    PubMed

    Nagaraj, Naveen K

    2016-09-01

    Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

  17. Pressure-tuned quantum criticality in the antiferromagnetic Kondo semimetal CeNi 2–δAs 2

    DOE PAGES

    Luo, Yongkang; Ronning, F.; Wakeham, N.; ...

    2015-10-19

    The easily tuned balance among competing interactions in Kondo-lattice metals allows access to a zero-temperature, continuous transition between magnetically ordered and disordered phases, a quantum-critical point (QCP). Indeed, these highly correlated electron materials are prototypes for discovering and exploring quantum-critical states. Theoretical models proposed to account for the strange thermodynamic and electrical transport properties that emerge around the QCP of a Kondo lattice assume the presence of an indefinitely large number of itinerant charge carriers. Here, we report a systematic transport and thermodynamic investigation of the Kondo-lattice system CeNi 2–δAs 2 (δ ≈ 0.28) as its antiferromagnetic order is tunedmore » by pressure and magnetic field to zero-temperature boundaries. These experiments show that the very small but finite carrier density of ~0.032 e –/formular unit in CeNi 2–δAs 2 leads to unexpected transport signatures of quantum criticality and the delayed development of a fully coherent Kondo-lattice state with decreasing temperature. Here, the small carrier density and associated semimetallicity of this Kondo-lattice material favor an unconventional, local-moment type of quantum criticality and raises the specter of the Nozières exhaustion idea that an insufficient number of conduction-electron spins to separately screen local moments requires collective Kondo screening.« less

  18. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    PubMed Central

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  19. Translational control of auditory imprinting and structural plasticity by eIF2α

    PubMed Central

    Batista, Gervasio; Johnson, Jennifer Leigh; Dominguez, Elena; Costa-Mattioli, Mauro; Pena, Jose L

    2016-01-01

    The formation of imprinted memories during a critical period is crucial for vital behaviors, including filial attachment. Yet, little is known about the underlying molecular mechanisms. Using a combination of behavior, pharmacology, in vivo surface sensing of translation (SUnSET) and DiOlistic labeling we found that, translational control by the eukaryotic translation initiation factor 2 alpha (eIF2α) bidirectionally regulates auditory but not visual imprinting and related changes in structural plasticity in chickens. Increasing phosphorylation of eIF2α (p-eIF2α) reduces translation rates and spine plasticity, and selectively impairs auditory imprinting. By contrast, inhibition of an eIF2α kinase or blocking the translational program controlled by p-eIF2α enhances auditory imprinting. Importantly, these manipulations are able to reopen the critical period. Thus, we have identified a translational control mechanism that selectively underlies auditory imprinting. Restoring translational control of eIF2α holds the promise to rejuvenate adult brain plasticity and restore learning and memory in a variety of cognitive disorders. DOI: http://dx.doi.org/10.7554/eLife.17197.001 PMID:28009255

  20. Development and Impact Evaluation of an E-Learning Radiation Oncology Module

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

    Alfieri, Joanne, E-mail: Joanne.alfieri@mail.mcgill.ca; Portelance, Lorraine; Souhami, Luis

    Purpose: Radiation oncologists are faced with the challenge of irradiating tumors to a curative dose while limiting toxicity to healthy surrounding tissues. This can be achieved only with superior knowledge of radiologic anatomy and treatment planning. Educational resources designed to meet these specific needs are lacking. A web-based interactive module designed to improve residents' knowledge and application of key anatomy concepts pertinent to radiotherapy treatment planning was developed, and its effectiveness was assessed. Methods and Materials: The module, based on gynecologic malignancies, was developed in collaboration with a multidisciplinary team of subject matter experts. Subsequently, a multi-centre randomized controlled studymore » was conducted to test the module's effectiveness. Thirty-six radiation oncology residents participated in the study; 1920 were granted access to the module (intervention group), and 17 in the control group relied on traditional methods to acquire their knowledge. Pretests and posttests were administered to all participants. Statistical analysis was carried out using paired t test, analysis of variance, and post hoc tests. Results: The randomized control study revealed that the intervention group's pretest and posttest mean scores were 35% and 52%, respectively, and those of the control group were 37% and 42%, respectively. The mean improvement in test scores was 17% (p < 0.05) for the intervention group and 5% (p = not significant) for the control group. Retrospective pretest and posttest surveys showed a statistically significant change on all measured module objectives. Conclusions: The use of an interactive e-learning teaching module for radiation oncology is an effective method to improve the radiologic anatomy knowledge and treatment planning skills of radiation oncology residents.« less

  1. Detecting cheaters without thinking: testing the automaticity of the cheater detection module.

    PubMed

    Van Lier, Jens; Revlin, Russell; De Neys, Wim

    2013-01-01

    Evolutionary psychologists have suggested that our brain is composed of evolved mechanisms. One extensively studied mechanism is the cheater detection module. This module would make people very good at detecting cheaters in a social exchange. A vast amount of research has illustrated performance facilitation on social contract selection tasks. This facilitation is attributed to the alleged automatic and isolated operation of the module (i.e., independent of general cognitive capacity). This study, using the selection task, tested the critical automaticity assumption in three experiments. Experiments 1 and 2 established that performance on social contract versions did not depend on cognitive capacity or age. Experiment 3 showed that experimentally burdening cognitive resources with a secondary task had no impact on performance on the social contract version. However, in all experiments, performance on a non-social contract version did depend on available cognitive capacity. Overall, findings validate the automatic and effortless nature of social exchange reasoning.

  2. Detecting Cheaters without Thinking: Testing the Automaticity of the Cheater Detection Module

    PubMed Central

    Van Lier, Jens; Revlin, Russell; De Neys, Wim

    2013-01-01

    Evolutionary psychologists have suggested that our brain is composed of evolved mechanisms. One extensively studied mechanism is the cheater detection module. This module would make people very good at detecting cheaters in a social exchange. A vast amount of research has illustrated performance facilitation on social contract selection tasks. This facilitation is attributed to the alleged automatic and isolated operation of the module (i.e., independent of general cognitive capacity). This study, using the selection task, tested the critical automaticity assumption in three experiments. Experiments 1 and 2 established that performance on social contract versions did not depend on cognitive capacity or age. Experiment 3 showed that experimentally burdening cognitive resources with a secondary task had no impact on performance on the social contract version. However, in all experiments, performance on a non-social contract version did depend on available cognitive capacity. Overall, findings validate the automatic and effortless nature of social exchange reasoning. PMID:23342012

  3. Evaluating an Online E-Module for Portuguese Primary Teachers: Trainees' Perceptions

    ERIC Educational Resources Information Center

    Pombo, L.; Smith, M.; Abelha, M.; Caixinha, H.; Costa, N.

    2012-01-01

    The work reported in this article is part of a wider project that aims to develop and implement a web-based, pan-European, in-service professional development platform for teachers to enhance their role in promoting education through science. This article aims to evaluate the implementation of the e-module on Assessment of Children's Learning in…

  4. Aquatic modules for bioregenerative life support systems: Developmental aspects based on the space flight results of the C.E.B.A. Mini Module

    NASA Astrophysics Data System (ADS)

    Bluem, S. V.

    The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) is an artificial aquatic ecosystem which contains teleost fishes, water snails, ammonia oxidizing bacteria and edible non-gravitropic water plants. It serves as a model for aquatic food production modules which are not seriously affected by microgravity and other space conditions. Its space flight version, the so-called C.E.B.AS. MINI-MODULE was already successfully tested in the STS-89 and STS 90 (NEUROLAB) missions.- I will be flown a third time in space with the STS 107 mission in July 2002. All- results obtained so far in space indicate that the basic concept of the system is more than suitable to drive forward its development. The C.E.B.A.S. MINI-MODULE is located within a middeck locker whith limited the space for additional components. These technical limitations allow only some modifications which lead to a maximum experiment time span of 120 days which is not long enough for the demanded scientifically essential multi-generation-experiments. This first necessary step is the development of "harvesting devices" for the different organisms. In the limited space of the plant bioreactor a high biomass production leads to self- shadowing effects which results in an uncontrolled degradation and increased oxygen consum ption by microorganisms which will endanger the fishes and snails. It was shown already that the latter reproduce excellently in space and that the reproductive functions of the fishes are not affected. Although the parent - offspring- cannibalism of the used ovoviviparous fish species (Xiphophorus helleri) serves as a regulating factor in population dynamics an uncontrolled snail reproduction will also induce an increased ox gen consumption per se and a high ammonia concentrationy in the water. If harvesting locks can be handled by astronauts in, e. g., 4w e e k- intervals their construction is not very difficult and basic technical solutions are already developed. The second problem is

  5. Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis*

    PubMed Central

    Inada, Masaki; Takita, Morichika; Yokoyama, Satoshi; Watanabe, Kenta; Tominari, Tsukasa; Matsumoto, Chiho; Hirata, Michiko; Maru, Yoshiro; Maruyama, Takayuki; Sugimoto, Yukihiko; Narumiya, Shuh; Uematsu, Satoshi; Akira, Shizuo; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato

    2015-01-01

    The stromal cells associated with tumors such as melanoma are significant determinants of tumor growth and metastasis. Using membrane-bound prostaglandin E synthase 1 (mPges1−/−) mice, we show that prostaglandin E2 (PGE2) production by host tissues is critical for B16 melanoma growth, angiogenesis, and metastasis to both bone and soft tissues. Concomitant studies in vitro showed that PGE2 production by fibroblasts is regulated by direct interaction with B16 cells. Autocrine activity of PGE2 further regulates the production of angiogenic factors by fibroblasts, which are key to the vascularization of both primary and metastatic tumor growth. Similarly, cell-cell interactions between B16 cells and host osteoblasts modulate mPGES-1 activity and PGE2 production by the osteoblasts. PGE2, in turn, acts to stimulate receptor activator of NF-κB ligand expression, leading to osteoclast differentiation and bone erosion. Using eicosanoid receptor antagonists, we show that PGE2 acts on osteoblasts and fibroblasts in the tumor microenvironment through the EP4 receptor. Metastatic tumor growth and vascularization in soft tissues was abrogated by an EP4 receptor antagonist. EP4-null Ptger4−/− mice do not support B16 melanoma growth. In vitro, an EP4 receptor antagonist modulated PGE2 effects on fibroblast production of angiogenic factors. Our data show that B16 melanoma cells directly influence host stromal cells to generate PGE2 signals governing neoangiogenesis and metastatic growth in bone via osteoclast erosive activity as well as angiogenesis in soft tissue tumors. PMID:26475855

  6. Middle School Engineering Problem Solving Using Traditional vs. E-PBL Module Instruction

    ERIC Educational Resources Information Center

    Baele, Loren C.

    2017-01-01

    This multiple methods (Denzin, 1978) study investigated two instructional approaches, traditional module and electronic Problem-Based Learning instruction (e-PBL), used within a middle school engineering classroom focused on the variables of engagement, content knowledge, student self-assessment and teacher assessment of problem solving solutions.…

  7. ROMPS critical design review. Volume 3: Furnace module design documentation

    NASA Technical Reports Server (NTRS)

    Dobbs, M. E.

    1992-01-01

    As part of the furnace module design documentation, the furnace module Easylab programs definitions and command variables are described. Also included are Easylab commands flow charts and fault conditions.

  8. Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by Ca2+ Sensitizers and a Ca2+ Sensitivity Blunting Phosphomimic, cTnT(T204E).

    PubMed

    Schlecht, William; Dong, Wen-Ji

    2017-10-18

    Several studies have suggested that conformational dynamics are important in the regulation of thin filament activation in cardiac troponin C (cTnC); however, little direct evidence has been offered to support these claims. In this study, a dye homodimerization approach is developed and implemented that allows the determination of the dynamic equilibrium between open and closed conformations in cTnC's hydrophobic cleft. Modulation of this equilibrium by Ca 2+ , cardiac troponin I (cTnI), cardiac troponin T (cTnT), Ca 2+ -sensitizers, and a Ca 2+ -desensitizing phosphomimic of cTnT (cTnT(T204E) is characterized. Isolated cTnC contained a small open conformation population in the absence of Ca 2+ that increased significantly upon the addition of saturating levels of Ca 2+ . This suggests that the Ca 2+ -induced activation of thin filament arises from an increase in the probability of hydrophobic cleft opening. The inclusion of cTnI increased the population of open cTnC, and the inclusion of cTnT had the opposite effect. Samples containing Ca 2+ -desensitizing cTnT(T204E) showed a slight but insignificant decrease in open conformation probability compared to samples with cardiac troponin T, wild type [cTnT(wt)], while Ca 2+ sensitizer treated samples generally increased open conformation probability. These findings show that an equilibrium between the open and closed conformations of cTnC's hydrophobic cleft play a significant role in tuning the Ca 2+ sensitivity of the heart.

  9. The Cylindrical Component Methodology Evaluation Module for MUVES-S2

    DTIC Science & Technology

    2017-04-01

    ARL-TR-7990 ● APR 2017 US Army Research Laboratory The Cylindrical Component Methodology Evaluation Module for MUVES-S2 by...Laboratory The Cylindrical Component Methodology Evaluation Module for MUVES-S2 by David S Butler, Marianne Kunkel, and Brian G Smith...Methodology Evaluation Module for MUVES-S2 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David S Butler, Marianne

  10. Kinetics, Ca2+ dependence, and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor nerve terminals

    NASA Technical Reports Server (NTRS)

    Chen, B. M.; Grinnell, A. D.

    1997-01-01

    Neurotransmitter release from frog motor nerve terminals is strongly modulated by change in muscle length. Over the physiological range, there is an approximately 10% increase in spontaneous and evoked release per 1% muscle stretch. Because many muscle fibers do not receive suprathreshold synaptic inputs at rest length, this stretch-induced enhancement of release constitutes a strong peripheral amplifier of the spinal stretch reflex. The stretch modulation of release is inhibited by peptides that block integrin binding of natural ligands. The modulation varies linearly with length, with a delay of no more than approximately 1-2 msec and is maintained constant at the new length. Moreover, the stretch modulation persists in a zero Ca2+ Ringer and, hence, is not dependent on Ca2+ influx through stretch activated channels. Eliminating transmembrane Ca2+ gradients and buffering intraterminal Ca2+ to approximately normal resting levels does not eliminate the modulation, suggesting that it is not the result of release of Ca2+ from internal stores. Finally, changes in temperature have no detectable effect on the kinetics of stretch-induced changes in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We conclude, therefore, that stretch does not act via second messenger pathways or a chemical modification of molecules involved in the release pathway. Instead, there is direct mechanical modulation of release. We postulate that tension on integrins in the presynaptic membrane is transduced mechanically into changes in the position or conformation of one or more molecules involved in neurotransmitter release, altering sensitivity to Ca2+ or the equilibrium for a critical reaction leading to vesicle fusion.

  11. The E(2) symmetry and quantum phase transition in the two-dimensional limit of the vibron model

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Pan, Feng; Liu, Yu-Xin; Draayer, J. P.

    2010-11-01

    We study in detail the relation between the two-dimensional Euclidean dynamical E(2) symmetry and the quantum phase transition in the two-dimensional limit of the vibron model, called the U(3) vibron model. Both geometric and algebraic descriptions of the U(3) vibron model show that structures of low-lying states at the critical point of the model with a quartic potential as its classical limit can be approximately described by the E(2) symmetry. We also fit the finite-size scaling exponent of the energy levels and E1 transition rates in the F(2) model, which is exactly the E(2) model but with truncation in its Hilbert subspace, as well as those at the critical point in the U(3) vibron model. The N-scaling power law around the critical point shows that the E(2) symmetry is well preserved even for cases with finite number of bosons. In addition, two kinds of experimentally accessible effective order parameters, such as the energy ratios E_{2_1}/E_{1_1}, E_{3_1}/E_{1_1} and E1 transition ratios \\frac{B(E1;2_1\\rightarrow 1_1)}{B(E1;1_1\\rightarrow 0_1)}, \\frac{B(E1;0_2\\rightarrow 1_1)}{B(E1;1_1\\rightarrow 0_1)}, are proposed to identify the second-order phase transition in such systems. Possible empirical examples exhibiting approximate E(2) symmetry are also presented.

  12. Block 2 solar cell module environmental test program

    NASA Technical Reports Server (NTRS)

    Holloway, K. L.

    1978-01-01

    Environmental tests were performed of on 76 solar cell modules produced by four different manufacturers. The following tests were performed: (1) 28 day temperature and humidity; (2) rain and icing; (3) salt fog; (4) sand and dust; (5) vacuum/steam/pressure; (6) fungus; (7) temperature/altitude; and (8) thermal shock. Environmental testing of the solar cell modules produced cracked cells, cracked encapsulant and encapsulant delaminations on various modules. In addition, there was some minor cell and frame corrosion.

  13. Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

    PubMed Central

    Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

    2013-01-01

    Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

  14. Airlock Battery Charge module

    NASA Image and Video Library

    2008-06-06

    S124-E-006858 (6 June 2008) --- Astronauts Greg Chamitoff, Expedition 17 flight engineer, and Karen Nyberg, STS-124 mission specialist, use the controls of the International Space Station's robotic Canadarm2 in the Destiny laboratory to maneuver the Kibo Japanese logistics module from atop the Harmony node to the top of the Kibo Japanese Pressurized Module.

  15. Global Carbon Cycle Modeling in GISS ModelE2 GCM

    NASA Astrophysics Data System (ADS)

    Aleinov, I. D.; Kiang, N. Y.; Romanou, A.; Romanski, J.

    2014-12-01

    Consistent and accurate modeling of the Global Carbon Cycle remains one of the main challenges for the Earth System Models. NASA Goddard Institute for Space Studies (GISS) ModelE2 General Circulation Model (GCM) was recently equipped with a complete Global Carbon Cycle algorithm, consisting of three integrated components: Ent Terrestrial Biosphere Model (Ent TBM), Ocean Biogeochemistry Module and atmospheric CO2 tracer. Ent TBM provides CO2 fluxes from the land surface to the atmosphere. Its biophysics utilizes the well-known photosynthesis functions of Farqhuar, von Caemmerer, and Berry and Farqhuar and von Caemmerer, and stomatal conductance of Ball and Berry. Its phenology is based on temperature, drought, and radiation fluxes, and growth is controlled via allocation of carbon from labile carbohydrate reserve storage to different plant components. Soil biogeochemistry is based on the Carnegie-Ames-Stanford (CASA) model of Potter et al. Ocean biogeochemistry module (the NASA Ocean Biogeochemistry Model, NOBM), computes prognostic distributions for biotic and abiotic fields that influence the air-sea flux of CO2 and the deep ocean carbon transport and storage. Atmospheric CO2 is advected with a quadratic upstream algorithm implemented in atmospheric part of ModelE2. Here we present the results for pre-industrial equilibrium and modern transient simulations and provide comparison to available observations. We also discuss the process of validation and tuning of particular algorithms used in the model.

  16. Device 2E6 (ACMS) Air Combat Maneuvering Simulator Instructor Console Review.

    DTIC Science & Technology

    1983-12-01

    While the device provides some new features which support training such as a debrief facility and a computer based instructor training module, the...Equipment Center, Orlando, FL (in printing). - 11 - -~.-. -- ~ --- NAVTRAEQUI PCEN 82-M-0767- 1 PROJECTORS DOE COMPUTER SYSTEMS Figure 1. General...arrangement (2E6) - 12 7 NAVTRAEQUIPCEN 82-M--0767-1 d. instructor stations, e. computer systems, ftarget model subsystem, g. debrief subsystem, h

  17. Optically tuned terahertz modulator based on annealed multilayer MoS2.

    PubMed

    Cao, Yapeng; Gan, Sheng; Geng, Zhaoxin; Liu, Jian; Yang, Yuping; Bao, Qiaoling; Chen, Hongda

    2016-03-08

    Controlling the propagation properties of terahertz waves is very important in terahertz technologies applied in high-speed communication. Therefore a new-type optically tuned terahertz modulator based on multilayer-MoS2 and silicon is experimentally demonstrated. The terahertz transmission could be significantly modulated by changing the power of the pumping laser. With an annealing treatment as a p-doping method, MoS2 on silicon demonstrates a triple enhancement of terahertz modulation depth compared with the bare silicon. This MoS2-based device even exhibited much higher modulation efficiency than the graphene-based device. We also analyzed the mechanism of the modulation enhancement originated from annealed MoS2, and found that it is different from that of graphene-based device. The unique optical modulating properties of the device exhibit tremendous promise for applications in terahertz switch.

  18. Cigarette smoke extract modulates human beta-defensin-2 and interleukin-8 expression in human gingival epithelial cells.

    PubMed

    Mahanonda, R; Sa-Ard-Iam, N; Eksomtramate, M; Rerkyen, P; Phairat, B; Schaecher, K E; Fukuda, M M; Pichyangkul, S

    2009-08-01

    Human gingival epithelial cells (HGECs) are continually exposed to oral bacteria and to other harmful agents. Their responses to stimuli are critical in maintaining periodontal homeostasis. The aim of this study was to investigate the modulating effect of cigarette smoke extract (CSE) on the innate immune responses of HGECs. Toll-like receptor (TLR) expression of HGECs was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of CSE or nicotine on the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) and the pro-inflammatory cytokine interleukin (IL)-8 in stimulated HGEC cultures was evaluated by RT-PCR and enzyme-linked immunosorbent assay. The HGECs expressed mRNA of TLRs 1, 2, 3, 5, 6, 9, 10, and minimally of TLR4, but not of TLRs 7 or 8. Stimulation of HGECs with highly purified TLR2, 3 or 5 ligands led to expression of hBD-2 and of IL-8. Enhancement of hBD-2 and IL-8 was observed in HGECs after combined stimulation with Porphyromonas gingivalis lipopolysaccharide (TLR2 ligand) and tumour necrosis factor-alpha, compared with stimulation using either agent alone. After CSE exposure, hBD-2 expression was markedly reduced in stimulated HGEC cultures, whereas IL-8 expression was markedly increased. These effects were also observed, but were markedly attenuated, upon nicotine treatment. Human gingival epithelial cells play a critical role in orchestrating the innate immune responses of periodontal tissue via TLR signalling. Our results represent the first demonstration that CSE can modulate HGEC function by suppressing hBD-2 and enhancing IL-8 production, and this may be, in part, a possible mechanism which promotes periodontal disease.

  19. The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell Size

    PubMed Central

    Artiles, Karen; Anastasia, Stephanie; McCusker, Derek; Kellogg, Douglas R.

    2009-01-01

    The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Δ cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates. PMID:19911052

  20. E-learning module on chronic low back pain in older adults: evidence of effect on medical student objective structured clinical examination performance.

    PubMed

    Weiner, Debra K; Morone, Natalia E; Spallek, Heiko; Karp, Jordan F; Schneider, Michael; Washburn, Carol; Dziabiak, Michael P; Hennon, John G; Elnicki, D Michael

    2014-06-01

    The Institute of Medicine has highlighted the urgent need to close undergraduate and graduate educational gaps in treating pain. Chronic low back pain (CLBP) is one of the most common pain conditions, and older adults are particularly vulnerable to potential morbidities associated with misinformed treatment. An e-learning case-based interactive module was developed at the University of Pittsburgh Center of Excellence in Pain Education, one of 12 National Institutes of Health-designated centers, to teach students important principles for evaluating and managing CLBP in older adults. A team of six experts in education, information technology, pain management, and geriatrics developed the module. Teaching focused on common errors, interactivity, and expert modeling and feedback. The module mimicked a patient encounter using a standardized patient (the older adult with CLBP) and a pain expert (the patient provider). Twenty-eight medical students were not exposed to the module (Group 1) and 27 were exposed (Group 2). Their clinical skills in evaluating CLBP were assessed using an objective structured clinical examination (OSCE). Mean scores were 62.0 ± 8.6 for Group 1 and 79.5 ± 10.4 for Group 2 (P < .001). Using an OSCE pass-fail cutoff score of 60%, 17 of 28 Group 1 students (60.7%) and 26 of 27 Group 2 students (96.3%) passed. The CLBP OSCE was one of 10 OSCE stations in which students were tested at the end of a Combined Ambulatory Medicine and Pediatrics Clerkship. There were no between-group differences in performance on eight of the other nine OSCE stations. This module significantly improved medical student clinical skills in evaluating CLBP. Additional research is needed to ascertain the effect of e-learning modules on more-advanced learners and on improving the care of older adults with CLBP. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  1. E-Learning Module on Chronic Low Back Pain in Older Adults: Evidence of Effect on Medical Student Objective Structured Clinical Examination Performance

    PubMed Central

    Weiner, Debra K.; Morone, Natalia E.; Spallek, Heiko; Karp, Jordan F.; Schneider, Michael; Washburn, Carol; Dziabiak, Michael P.; Hennon, John G.; Elnicki, D. Michael

    2015-01-01

    The Institute of Medicine has highlighted the urgent need to close undergraduate and graduate educational gaps in treating pain. Chronic low back pain (CLBP) is one of the most common pain conditions, and older adults are particularly vulnerable to potential morbidities associated with misinformed treatment. An e-learning case-based interactive module was developed at the University of Pittsburgh Center of Excellence in Pain Education, one of 12 National Institutes of Health–designated centers, to teach students important principles for evaluating and managing CLBP in older adults. A team of six experts in education, information technology, pain management, and geriatrics developed the module. Teaching focused on common errors, interactivity, and expert modeling and feedback. The module mimicked a patient encounter using a standardized patient (the older adult with CLBP) and a pain expert (the patient provider). Twenty-eight medical students were not exposed to the module (Group 1) and 27 were exposed (Group 2). Their clinical skills in evaluating CLBP were assessed using an objective structured clinical examination (OSCE). Mean scores were 62.0 ± 8.6 for Group 1 and 79.5 ± 10.4 for Group 2 (P < .001). Using an OSCE pass–fail cutoff score of 60%, 17 of 28 Group 1 students (60.7%) and 26 of 27 Group 2 students (96.3%) passed. The CLBP OSCE was one of 10 OSCE stations in which students were tested at the end of a Combined Ambulatory Medicine and Pediatrics Clerkship. There were no between-group differences in performance on eight of the other nine OSCE stations. This module significantly improved medical student clinical skills in evaluating CLBP. Additional research is needed to ascertain the effect of e-learning modules on more-advanced learners and on improving the care of older adults with CLBP. PMID:24833496

  2. 6.2-GHz modulated terahertz light detection using fast terahertz quantum well photodetectors.

    PubMed

    Li, Hua; Wan, Wen-Jian; Tan, Zhi-Yong; Fu, Zhang-Long; Wang, Hai-Xia; Zhou, Tao; Li, Zi-Ping; Wang, Chang; Guo, Xu-Guang; Cao, Jun-Cheng

    2017-06-14

    The fast detection of terahertz radiation is of great importance for various applications such as fast imaging, high speed communications, and spectroscopy. Most commercial products capable of sensitively responding the terahertz radiation are thermal detectors, i.e., pyroelectric sensors and bolometers. This class of terahertz detectors is normally characterized by low modulation frequency (dozens or hundreds of Hz). Here we demonstrate the first fast semiconductor-based terahertz quantum well photodetectors by carefully designing the device structure and microwave transmission line for high frequency signal extraction. Modulation response bandwidth of gigahertz level is obtained. As an example, the 6.2-GHz modulated terahertz light emitted from a Fabry-Pérot terahertz quantum cascade laser is successfully detected using the fast terahertz quantum well photodetector. In addition to the fast terahertz detection, the technique presented in this work can also be used for optically characterizing the frequency stability of terahertz quantum cascade lasers, heterodyne detections and photomixing applications.

  3. Aquatic modules for bioregenerative life support systems based on the C.E.B.A.S. biotechnology

    NASA Astrophysics Data System (ADS)

    Bluem, Volker; Paris, Frank

    2001-03-01

    Most concepts for bioregenerative life support systems are based on edible higher land plants which create some problems with growth and seed generation under space conditions. Animal protein production is mostly neglected because of the tremendous waste management problems with tetrapods under reduced weightlessness. Therefore, the "Closed Equilibrated Biological Aquatic System" (C.E.B.A.S.) was developed which represents an artificial aquatic ecosystem containing aquatic organisms which are adpated at all to "near weightlessness conditions" (fishes Xiphophorus helleri, water snails Biomphalaria glabrata, ammonia oxidizing bacteria and the rootless non-gravitropic edible water plant Ceratophyllum demersum). Basically the C.E.B.A.S. consists of 4 subsystems: a ZOOLOGICASL COMPONENT (animal aquarium), a BOTANICAL COMPONENT (aquatic plant bioreactor), a MICROBIAL COMPONENT (bacteria filter) and an ELECTRONICAL COMPONENT (data acquisition and control unit). Superficially, the function principle appears simple: the plants convert light energy into chemical energy via photosynthesis thus producing biomass and oxygen. The animals and microorganisms use the oxygen for respiration and produce the carbon dioxide which is essential for plant photosynthesis. The ammonia ions excreted by the animals are converted by the bacteria to nitrite and then to nitrate ions which serve as a nitrogen source for the plants. Other essential ions derive from biological degradation of animal waste products and dead organic matter. The C.E.B.A.S. exists in 2 basic versions: the original C.E.B.A.S. with a volume of 150 liters and a self-sustaining standing time of more than 13 month and the so-called C.E.B.A.S. MINI MODULE with a volume of about 8.5 liters. In the latter there is no closed food loop by reasons of available space so that animal food has to be provided via an automated feeder. This device was flown already successfully on the STS-89 and STS-90 spaceshuttle missions and the

  4. Exciton Emission Intensity Modulation of Monolayer MoS2 via Au Plasmon Coupling

    PubMed Central

    Mukherjee, B.; Kaushik, N.; Tripathi, Ravi P. N.; Joseph, A. M.; Mohapatra, P. K.; Dhar, S.; Singh, B. P.; Kumar, G. V. Pavan; Simsek, E.; Lodha, S.

    2017-01-01

    Modulation of photoluminescence of atomically thin transition metal dichalcogenide two-dimensional materials is critical for their integration in optoelectronic and photonic device applications. By coupling with different plasmonic array geometries, we have shown that the photoluminescence intensity can be enhanced and quenched in comparison with pristine monolayer MoS2. The enhanced exciton emission intensity can be further tuned by varying the angle of polarized incident excitation. Through controlled variation of the structural parameters of the plasmonic array in our experiment, we demonstrate modulation of the photoluminescence intensity from nearly fourfold quenching to approximately threefold enhancement. Our data indicates that the plasmonic resonance couples to optical fields at both, excitation and emission bands, and increases the spontaneous emission rate in a double spacing plasmonic array structure as compared with an equal spacing array structure. Furthermore our experimental results are supported by numerical as well as full electromagnetic wave simulations. This study can facilitate the incorporation of plasmon-enhanced transition metal dichalcogenide structures in photodetector, sensor and light emitter applications. PMID:28134260

  5. Parts Counter. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Snyder, James A.

    These 23 Student Training Modules on parts counter comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 571.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  6. Floor Covering. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Hamblen, Ron

    These 21 Student Training Modules on floor covering comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 565.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of the…

  7. Cement Finishing. Pre-Apprenticeship Phase 2 Training. Student Training Modules.

    ERIC Educational Resources Information Center

    Nama, Joe

    These 20 Student Training Modules on cement finishing comprise one of nine sets of self-paced learning modules developed for Pre-Apprenticeship Phase 2 Training. (A companion instructor's guide is available separately as CE 031 575.) The modules are designed to impart trade knowledge and skills to the student. Each module contains some or all of…

  8. A Prospective Cohort Study Using e-Learning Modules as a Supplemental Teaching Resource for Obstetrics and Gynaecology Clerkship Students.

    PubMed

    Kim, Jason; Coolen, Jillian

    2015-09-01

    Increasing enrolment in medical schools in Canada has necessitated the development of distributed clinical learning sites to provide appropriate clinical experience. The Faculty of Medicine at Dalhousie University has clinical clerkship sites distributed across Nova Scotia, New Brunswick, and Prince Edward Island, with diverse educational exposures. This study was designed to examine the influence of online learning modules, developed to standardize learning across education sites during the clinical clerkship, on the acquisition of knowledge by medical students during their obstetrics and gynaecology clerkship rotation. The third year medical school class was divided into two natural cohorts for the purposes of this study. Group 1 had their obstetrics and gynaecology rotation from September 2012 to March 2013 (n = 54), and Group 2 had their rotation from April to September 2013 (n = 60). All students were given the opportunity to complete an online formative examination before their summative multiple choice examination; only Group 2 students had access to six obstetrics and gynaecology e-learning modules, upon which the formative examination was based. Forty-seven students in Group 1 (87%) and 45 students in Group 2 (75%) completed the formative examination, with an overall participation rate of 81%. There was no difference in median scores between Group 1 (score 9, IQR 8 to 10) and Group 2 (score 9, IQR 8 to 11, P = 0.08). Having access to six e-learning modules did not improve the third year medical students' scores on a formative examination completed before their summative multiple choice examination.

  9. Pharmacologic modulation of ACE2 expression.

    PubMed

    Soler, María José; Barrios, Clara; Oliva, Raymond; Batlle, Daniel

    2008-10-01

    Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.

  10. Mitochondrial Ca{sup 2+} uniporter is critical for store-operated Ca{sup 2+} entry-dependent breast cancer cell migration

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

    Tang, Shihao; Guangzhou No.12 Hospital, Guangzhou; Wang, Xubu

    2015-02-27

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca{sup 2+} uniporter (MCU), a regulator of mitochondrial Ca{sup 2+} uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-inducedmore » store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. - Highlights: • MCU is correlated to metastasis and invasive breast cancer. • MCU inhibition abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or TG-induced SOCE. • Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. • MCU plays a critical role in MDA-MB-231 cell migration by regulating SOCE.« less

  11. Light directs zebrafish period2 expression via conserved D and E boxes.

    PubMed

    Vatine, Gad; Vallone, Daniela; Appelbaum, Lior; Mracek, Philipp; Ben-Moshe, Zohar; Lahiri, Kajori; Gothilf, Yoav; Foulkes, Nicholas S

    2009-10-01

    For most species, light represents the principal environmental signal for entraining the endogenous circadian clock. The zebrafish is a fascinating vertebrate model for studying this process since unlike mammals, direct exposure of most of its tissues to light leads to local clock entrainment. Importantly, light induces the expression of a set of genes including certain clock genes in most zebrafish cell types in vivo and in vitro. However, the mechanism linking light to gene expression remains poorly understood. To elucidate this key mechanism, here we focus on how light regulates transcription of the zebrafish period2 (per2) gene. Using transgenic fish and stably transfected cell line-based assays, we define a Light Responsive Module (LRM) within the per2 promoter. The LRM lies proximal to the transcription start site and is both necessary and sufficient for light-driven gene expression and also for a light-dependent circadian clock regulation. Curiously, the LRM sequence is strongly conserved in other vertebrate per2 genes, even in species lacking directly light-sensitive peripheral clocks. Furthermore, we reveal that the human LRM can substitute for the zebrafish LRM to confer light-regulated transcription in zebrafish cells. The LRM contains E- and D-box elements that are critical for its function. While the E-box directs circadian clock regulation by mediating BMAL/CLOCK activity, the D-box confers light-driven expression. The zebrafish homolog of the thyrotroph embryonic factor binds efficiently to the LRM D-box and transactivates expression. We demonstrate that tef mRNA levels are light inducible and that knock-down of tef expression attenuates light-driven transcription from the per2 promoter in vivo. Together, our results support a model where a light-dependent crosstalk between E- and D-box binding factors is a central determinant of per2 expression. These findings extend the general understanding of the mechanism whereby the clock is entrained by light

  12. Integrin-linked kinase and ELMO2 modulate recycling endosomes in keratinocytes.

    PubMed

    Ho, Ernest; Ivanova, Iordanka A; Dagnino, Lina

    2016-12-01

    The formation of tight cell-cell junctions is essential in the epidermis for its barrier properties. In this tissue, keratinocytes follow a differentiation program tightly associated with their movement from the innermost basal to the outer suprabasal layers, and with changes in their cell-cell adhesion profile. Intercellular adhesion in keratinocytes is mediated through cell-cell contacts, including E-cadherin-based adherens junctions. Although the mechanisms that mediate E-cadherin delivery to the plasma membrane have been widely studied in simple epithelia, this process is less well understood in the stratified epidermis. In this study, we have investigated the role of Engulfment and Cell Motility 2 (ELMO2) and integrin-linked kinase (ILK) in the positioning of E-cadherin-containing recycling endosomes during establishment of cell-cell contacts in differentiating keratinocytes. We now show that induction of keratinocyte differentiation by Ca 2+ is accompanied by localization of ELMO2 and ILK to Rab4- and Rab11a-containing recycling endosomes. The positioning of long-loop Rab11a-positive endosomes at areas adjacent to cell-cell contacts is disrupted in ELMO2- or ILK-deficient keratinocytes, and is associated with impaired localization of E-cadherin to cell borders. Our studies show a previously unrecognized role for ELMO2 and ILK in modulation of endosomal positioning, which may play key roles in epidermal sheet maintenance and permeability barrier function. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. An E-Learning Module to Improve Nongenetic Health Professionals’ Assessment of Colorectal Cancer Genetic Risk: Feasibility Study

    PubMed Central

    Aalfs, Cora M; Dekker, Evelien; Tanis, Pieter J; Smets, Ellen M

    2017-01-01

    Background Nongenetic health providers may lack the relevant knowledge, experience, and communication skills to adequately detect familial colorectal cancer (CRC), despite a positive attitude toward the assessment of history of cancer in a family. Specific training may enable them to more optimally refer patients to genetic counseling. Objective The aim of this study was to develop an e-learning module for gastroenterologists and surgeons (in training) aimed at improving attitudes, knowledge, and comprehension of communication skills, and to assess the feasibility of the e-learning module for continued medical education of these specialists. Methods A focus group helped to inform the development of a training framework. The e-learning module was then developed, followed by a feasibility test among a group of surgeons-in-training (3rd- and 4th-year residents) and then among gastroenterologists, using pre- and posttest questionnaires. Results A total of 124 surgeons-in-training and 14 gastroenterologists participated. The e-learning was positively received (7.5 on a scale of 1 to 10). Between pre- and posttest, attitude increased significantly on 6 out of the 10 items. Mean test score showed that knowledge and comprehension of communication skills improved significantly from 49% to 72% correct at pretest to 67% to 87% correct at posttest. Conclusions This study shows the feasibility of a problem-based e-learning module to help surgeons-in-training and gastroenterologists in recognizing a hereditary predisposition in patients with CRC. The e-learning led to improvements in attitude toward the assessment of cancer family history, knowledge on criteria for referral to genetic counseling for CRC, and comprehension of communication skills. PMID:29254907

  14. The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

    PubMed Central

    Bow, Eric W.; Rimoldi, John M.

    2016-01-01

    The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

  15. Aquatic modules for bioregenerative life support systems: Developmental aspects based on the space flight results of the C.E.B.A.S. mini-module

    NASA Astrophysics Data System (ADS)

    Blüm, V.

    The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) is an artificial aquatic ecosystem which contains teleost fishes, water snails, ammonia oxidizing bacteria and edible non-gravitropic water plants. It serves as a model for aquatic food production modules which are not seriously affected by microgravity and other space conditions. Its space flight version, the so-called C.E.B.A.S. MINI-MODULE was already successfidly tested in the STS-89 and STS-90 (NEUROLAB) missions. It will be flown a third time in space with the STS-107 mission in January 2003. All results obtained so far in space indicate that the basic concept of the system is more than suitable to drive forward its development. The C.E.B.A.S. MINI-MODULE is located within a middeck locker with limited space for additional components. These technical limitations allow only some modifications which lead to a maximum experiment time span of 120 days which is not long enough for scientifically essential multi-generation-experiments. The first necessary step is the development of "harvesting devices" for the different organisms. In the limited space of the plant bioreactor a high biomass production leads to self-shadowing effects which results in an uncontrolled degradation and increased oxygen consumption by microorganisms which will endanger the fishes and snails. It was shown already that the latter reproduce excellently in space and that the reproductive functions of the fish species are not affected. Although the parent-offspring-cannibalism of the ovoviviparous fish species ( Xiphophorus helleri) serves as a regulating factor in population dynamics an uncontrolled snail reproduction will also induce an increased oxygen consumption per se and a high ammonia concentration in the water. If harvesting locks can be handled by astronauts in, e. g., 4-week intervals their construction is not very difficult and basic technical solutions are already developed. The second problem is the feeding of the

  16. A critical role of striatal A2A R-mGlu5 R interactions in modulating the psychomotor and drug-seeking effects of methamphetamine.

    PubMed

    Wright, Sherie R; Zanos, Panos; Georgiou, Polymnia; Yoo, Ji-Hoon; Ledent, Catherine; Hourani, Susanna M; Kitchen, Ian; Winsky-Sommerer, Raphaelle; Bailey, Alexis

    2016-07-01

    Addiction to psychostimulants is a major public health problem with no available treatment. Adenosine A2A receptors (A2A R) co-localize with metabotropic glutamate 5 receptors (mGlu5 R) in the striatum and functionally interact to modulate behaviours induced by addictive substances, such as alcohol. Using genetic and pharmacological antagonism of A2A R in mice, we investigated whether A2A R-mGlu5 R interaction can regulate the locomotor, stereotypic and drug-seeking effect of methamphetamine and cocaine, two drugs that exhibit distinct mechanism of action. Genetic deletion of A2A R, as well as combined administration of sub-threshold doses of the selective A2A R antagonist (SCH 58261, 0.01 mg/kg, i.p.) with the mGlu5 R antagonist, 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (0.01 mg/kg, i.p.), prevented methamphetamine- but not cocaine-induced hyperactivity and stereotypic rearing behaviour. This drug combination also prevented methamphetamine-rewarding effects in a conditioned-place preference paradigm. Moreover, mGlu5 R binding was reduced in the nucleus accumbens core of A2A R knockout (KO) mice supporting an interaction between these receptors in a brain region crucial in mediating addiction processes. Chronic methamphetamine, but not cocaine administration, resulted in a significant increase in striatal mGlu5 R binding in wild-type mice, which was absent in the A2A R KO mice. These data are in support of a critical role of striatal A2A R-mGlu5 R functional interaction in mediating the ambulatory, stereotypic and reinforcing effects of methamphetamine but not cocaine-induced hyperlocomotion or stereotypy. The present study highlights a distinct and selective mechanistic role for this receptor interaction in regulating methamphetamine-induced behaviours and suggests that combined antagonism of A2A R and mGlu5 R may represent a novel therapy for methamphetamine addiction. © 2015 Society for the Study of Addiction.

  17. Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis.

    PubMed

    Inada, Masaki; Takita, Morichika; Yokoyama, Satoshi; Watanabe, Kenta; Tominari, Tsukasa; Matsumoto, Chiho; Hirata, Michiko; Maru, Yoshiro; Maruyama, Takayuki; Sugimoto, Yukihiko; Narumiya, Shuh; Uematsu, Satoshi; Akira, Shizuo; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato

    2015-12-11

    The stromal cells associated with tumors such as melanoma are significant determinants of tumor growth and metastasis. Using membrane-bound prostaglandin E synthase 1 (mPges1(-/-)) mice, we show that prostaglandin E2 (PGE2) production by host tissues is critical for B16 melanoma growth, angiogenesis, and metastasis to both bone and soft tissues. Concomitant studies in vitro showed that PGE2 production by fibroblasts is regulated by direct interaction with B16 cells. Autocrine activity of PGE2 further regulates the production of angiogenic factors by fibroblasts, which are key to the vascularization of both primary and metastatic tumor growth. Similarly, cell-cell interactions between B16 cells and host osteoblasts modulate mPGES-1 activity and PGE2 production by the osteoblasts. PGE2, in turn, acts to stimulate receptor activator of NF-κB ligand expression, leading to osteoclast differentiation and bone erosion. Using eicosanoid receptor antagonists, we show that PGE2 acts on osteoblasts and fibroblasts in the tumor microenvironment through the EP4 receptor. Metastatic tumor growth and vascularization in soft tissues was abrogated by an EP4 receptor antagonist. EP4-null Ptger4(-/-) mice do not support B16 melanoma growth. In vitro, an EP4 receptor antagonist modulated PGE2 effects on fibroblast production of angiogenic factors. Our data show that B16 melanoma cells directly influence host stromal cells to generate PGE2 signals governing neoangiogenesis and metastatic growth in bone via osteoclast erosive activity as well as angiogenesis in soft tissue tumors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Endeavour's payload bay with the Raphaello module and Canadarm 2

    NASA Image and Video Library

    2001-04-20

    S100-E-5015 (20 April 2001) --- One of the crew members of STS-100 aimed a digital still camera through Endeavour's aft flight deck windows to record this image of the cargo bay, backdropped against a scene of black space and Earth's horizon. Housed in the bay, beyond the docking mechanism in the foreground, is the Italian Space Agency-provided Raffaello cargo module, which is carrying several tons of equipment for the Expedition Two crew and racks of hardware for installation in Destiny which will be used for scientific research in the future. Raffaello, which is the second of three such logistics modules, will be berthed to the ISS on April 23 so its contents can be transferred to the station throughout the course of docked operations. Also in the bay is the 57-foot-long Canadarm2, which will be mounted on the Destiny Laboratory for future station assembly work. Endeavour's Canadian-built Remote Manipulator System (RMS) arm can be seen in its berthed position on the port side of the payload bay.

  19. Endeavour's payload bay with the Raphaello module and Canadarm 2

    NASA Image and Video Library

    2001-04-20

    S100-E-5018 (20 April 2001) --- One of the crew members of STS-100 aimed a digital still camera through Endeavour's aft flight deck windows to record this image of the cargo bay, backdropped against a scene of black space and Earth's horizon. Housed in the bay, beyond the docking mechanism in the foreground, is the Italian Space Agency-provided Raffaello cargo module, which is carrying several tons of equipment for the Expedition Two crew and racks of hardware for installation in Destiny which will be used for scientific research in the future. Raffaello, which is the second of three such logistics modules, will be berthed to the ISS on April 23 so its contents can be transferred to the station throughout the course of docked operations. Also in the bay is the 57-foot-long Canadarm2, which will be mounted on the Destiny Laboratory for future station assembly work. Endeavour's Canadian-built Remote Manipulator System (RMS) arm can be seen in its berthed position on the port side of the payload bay.

  20. Endeavour's payload bay with the Raphaello module and Canadarm 2

    NASA Image and Video Library

    2001-04-20

    S100-E-5002 (20 April 2001) --- One of the crew members of STS-100 aimed a digital still camera through Endeavour's aft flight deck windows to record this image of the cargo bay, backdropped against a scene of black space and Earth's horizon. Housed in the bay, beyond the docking mechanism in the foreground, is the Italian Space Agency-provided Raffaello cargo module, which is carrying several tons of equipment for the Expedition Two crew and racks of hardware for installation in Destiny which will be used for scientific research in the future. Raffaello, which is the second of three such logistics modules, will be berthed to the ISS on April 23 so its contents can be transferred to the station throughout the course of docked operations. Also in the bay is the 57-foot-long Canadarm2, which will be mounted on the Destiny Laboratory for future station assembly work. Endeavour's Canadian-built Remote Manipulator System (RMS) arm can be seen in its berthed position on the port side of the payload bay.

  1. Endeavour's payload bay with the Raphaello module and Canadarm 2

    NASA Image and Video Library

    2001-04-20

    S100-E-5017 (20 April 2001) --- One of the crew members of STS-100 aimed a digital still camera through Endeavour's aft flight deck windows to record this image of the cargo bay, backdropped against a scene of black space and Earth's horizon. Housed in the bay, beyond the docking mechanism in the foreground, is the Italian Space Agency-provided Raffaello cargo module, which is carrying several tons of equipment for the Expedition Two crew and racks of hardware for installation in Destiny which will be used for scientific research in the future. Raffaello, which is the second of three such logistics modules, will be berthed to the ISS on April 23 so its contents can be transferred to the station throughout the course of docked operations. Also in the bay is the 57-foot-long Canadarm2, which will be mounted on the Destiny Laboratory for future station assembly work. Endeavour's Canadian-built Remote Manipulator System (RMS) arm can be seen in its berthed position on the port side of the payload bay.

  2. Baicalin Ameliorates Liver Injury Induced by Chronic plus Binge Ethanol Feeding by Modulating Oxidative Stress and Inflammation via CYP2E1 and NRF2 in Mice

    PubMed Central

    He, Ping; Wu, Yafeng; Shun, Jianchao; Liang, Yaodong; Cheng, Mingliang

    2017-01-01

    Alcoholic liver injury leads to serious complication including death. The potential role of baicalin at the transcription level in mice model of alcohol injury is not known yet. In this study, we examined the effect of baicalin against chronic plus binge ethanol model in mice and understanding the mechanism of protection. Liver function, histology, steatosis, inflammation, NF-κB activity, oxidative stress sources, nuclear translocation of NRF2 transcription factor, and cell death were assessed. Treatment with baicalin ameliorated ethanol-induced oxidative stress, inflammation, and cell death. Baicalin attenuated ethanol-induced proinflammatory molecules such as TNF-α, IL-1β, MIP-2, and MCP-1 and reversed redox-sensitive transcription factor NF-κB activation. Baicalin also modulated Kupffer cell activation in vitro. Baicalin inhibited ethanol-induced expression of reactive oxygen species (ROS) generating enzymes NOX2, p67phox, xanthine oxidase, and iNOS in addition to CYP2E1 activities. Baicalin also enhanced ethanol-induced NRF2 nuclear translocation and increased downstream target gene HO-1 as antioxidant defense. Finally, baicalin reduced significant apoptotic and necrotic cell death. Our study suggests that baicalin ameliorates chronic plus binge ethanol-induced liver injury involving molecular crosstalk of multiple pathways at the transcriptional level and through upregulation of antioxidant defense mechanism. PMID:28951767

  3. Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

    NASA Astrophysics Data System (ADS)

    Weinberg, Rebecca

    The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1

  4. Biosphere 2 test module experimentation program

    NASA Technical Reports Server (NTRS)

    Alling, Abigail; Leigh, Linda S.; Maccallum, Taber; Alvarez-Romo, Norberto

    1990-01-01

    The Biosphere 2 Test Module is a facility which has the capability to do either short or long term closures: five month closures with plants were conducted. Also conducted were investigations of specific problems, such as trace gas purification by bioregenerative systems by in-putting a fixed concentration of a gas and observing its uptake over time. In other Test Module experiments, the concentration of one gas was changed to observe what effects this has on other gases present or on the system. The science of biospherics which encompasses the study of closed biological systems provides an opening into the future in space as well as in the Earth's biosphere.

  5. Quantifying translational coupling in E. coli synthetic operons using RBS modulation and fluorescent reporters.

    PubMed

    Levin-Karp, Ayelet; Barenholz, Uri; Bareia, Tasneem; Dayagi, Michal; Zelcbuch, Lior; Antonovsky, Niv; Noor, Elad; Milo, Ron

    2013-06-21

    Translational coupling is the interdependence of translation efficiency of neighboring genes encoded within an operon. The degree of coupling may be quantified by measuring how the translation rate of a gene is modulated by the translation rate of its upstream gene. Translational coupling was observed in prokaryotic operons several decades ago, but the quantitative range of modulation translational coupling leads to and the factors governing this modulation were only partially characterized. In this study, we systematically quantify and characterize translational coupling in E. coli synthetic operons using a library of plasmids carrying fluorescent reporter genes that are controlled by a set of different ribosome binding site (RBS) sequences. The downstream gene expression level is found to be enhanced by the upstream gene expression via translational coupling with the enhancement level varying from almost no coupling to over 10-fold depending on the upstream gene's sequence. Additionally, we find that the level of translational coupling in our system is similar between the second and third locations in the operon. The coupling depends on the distance between the stop codon of the upstream gene and the start codon of the downstream gene. This study is the first to systematically and quantitatively characterize translational coupling in a synthetic E. coli operon. Our analysis will be useful in accurate manipulation of gene expression in synthetic biology and serves as a step toward understanding the mechanisms involved in translational expression modulation.

  6. An E-Learning Module to Improve Nongenetic Health Professionals' Assessment of Colorectal Cancer Genetic Risk: Feasibility Study.

    PubMed

    Douma, Kirsten Freya Lea; Aalfs, Cora M; Dekker, Evelien; Tanis, Pieter J; Smets, Ellen M

    2017-12-18

    Nongenetic health providers may lack the relevant knowledge, experience, and communication skills to adequately detect familial colorectal cancer (CRC), despite a positive attitude toward the assessment of history of cancer in a family. Specific training may enable them to more optimally refer patients to genetic counseling. The aim of this study was to develop an e-learning module for gastroenterologists and surgeons (in training) aimed at improving attitudes, knowledge, and comprehension of communication skills, and to assess the feasibility of the e-learning module for continued medical education of these specialists. A focus group helped to inform the development of a training framework. The e-learning module was then developed, followed by a feasibility test among a group of surgeons-in-training (3rd- and 4th-year residents) and then among gastroenterologists, using pre- and posttest questionnaires. A total of 124 surgeons-in-training and 14 gastroenterologists participated. The e-learning was positively received (7.5 on a scale of 1 to 10). Between pre- and posttest, attitude increased significantly on 6 out of the 10 items. Mean test score showed that knowledge and comprehension of communication skills improved significantly from 49% to 72% correct at pretest to 67% to 87% correct at posttest. This study shows the feasibility of a problem-based e-learning module to help surgeons-in-training and gastroenterologists in recognizing a hereditary predisposition in patients with CRC. The e-learning led to improvements in attitude toward the assessment of cancer family history, knowledge on criteria for referral to genetic counseling for CRC, and comprehension of communication skills. ©Kirsten Freya Lea Douma, Cora M Aalfs, Evelien Dekker, Pieter J Tanis, Ellen M Smets. Originally published in JMIR Medical Education (http://mededu.jmir.org), 18.12.2017.

  7. Lessons from interprofessional e-learning: piloting a care of the elderly module.

    PubMed

    Juntunen, Anitta; Heikkinen, Eija

    2004-08-01

    Educating health care professionals is a key issue in the provision of quality healthcare services. Interprofessional education has been suggested as a means of meeting this challenge. Four Finnish polytechnics providing education for nurses, social workers and physiotherapists wished to develop the content and methods of teaching the care of the elderly by collaboratively creating and implementing an interprofessional module of 15 European Credit Transfer units, using e-learning. This paper examines the planning and assessment of the impact of the pilot module. The web-based environment eminently suited teaching interprofessional care of the elderly. It supported content and methodological development and renewal of the module. It enabled discussion and collaboration between nursing, social work and rehabilitation teachers and students from the Polytechnics which are located in different parts of Finland. However, it became evident during the pilot that the most crucial challenges of the web-based pedagogy were in the ability of the teacher to supervise, support and motivate students and the organisation of interprofessional learning offered by collaborating institutions.

  8. Organisational Issues for E-Learning: Critical Success Factors as Identified by HE Practitioners

    ERIC Educational Resources Information Center

    McPherson, Maggie; Nunes, Miguel Baptista

    2006-01-01

    Purpose: The purpose of this paper is to report on a research project that identified organisational critical success factors (CSFs) for e-learning implementation in higher education (HE). These CSFs can be used as a theoretical foundation upon which to base decision-making and strategic thinking about e-learning. Design/methodology/approach: The…

  9. Localized surface plasmon resonance modulation of totally encapsulated VO2/Au/VO2 composite structure

    NASA Astrophysics Data System (ADS)

    Liang, Jiran; Guo, Jinbang; Zhao, Yirui; Zhang, Ying; Su, Tianyu

    2018-07-01

    We design and fabricate a totally encapsulated VO2/Au/VO2 composite structure which is aimed to improve the tunability of the localized surface plasmon resonance (LSPR) peak. In this work, the structure will ensure all the Au NPs’ resonant electric field area is filled with VO2. The modulation range of the totally encapsulated structure is larger than that of the semi-coated structure. To further improve the modulation range, we also explore the VO2 thickness dependence of the structure’s LSPR modulation. With the increase of the top layer VO2 thin film thickness, the modulation range becomes larger. When the thickness is about 80 nm, the absorption peak achieves a largest shift of 112 nm. FDTD solution and equivalent model of series capacitor are used to explain the phenomenon. These results will contribute to the area of metamaterial electromagnetic wave absorber and other fields.

  10. Localized surface plasmon resonance modulation of totally encapsulated VO2/Au/VO2 composite structure.

    PubMed

    Liang, Jiran; Guo, Jinbang; Zhao, Yirui; Zhang, Ying; Su, Tianyu

    2018-07-06

    We design and fabricate a totally encapsulated VO 2 /Au/VO 2 composite structure which is aimed to improve the tunability of the localized surface plasmon resonance (LSPR) peak. In this work, the structure will ensure all the Au NPs' resonant electric field area is filled with VO 2 . The modulation range of the totally encapsulated structure is larger than that of the semi-coated structure. To further improve the modulation range, we also explore the VO 2 thickness dependence of the structure's LSPR modulation. With the increase of the top layer VO 2 thin film thickness, the modulation range becomes larger. When the thickness is about 80 nm, the absorption peak achieves a largest shift of 112 nm. FDTD solution and equivalent model of series capacitor are used to explain the phenomenon. These results will contribute to the area of metamaterial electromagnetic wave absorber and other fields.

  11. HPV-18 E6 mutants reveal p53 modulation of viral DNA amplification in organotypic cultures

    PubMed Central

    Kho, Eun-Young; Wang, Hsu-Kun; Banerjee, N. Sanjib; Broker, Thomas R.; Chow, Louise T.

    2013-01-01

    Human papillomaviruses (HPVs) amplify in differentiated strata of a squamous epithelium. The HPV E7 protein destabilizes the p130/retinoblastoma susceptibility protein family of tumor suppressors and reactivates S-phase reentry, thereby facilitating viral DNA amplification. The high-risk HPV E6 protein destabilizes the p53 tumor suppressor and many other host proteins. However, the critical E6 targets relevant to viral DNA amplification have not been identified, because functionally significant E6 mutants are not stably maintained in transfected cells. Using Cre-loxP recombination, which efficiently generates HPV genomic plasmids in transfected primary human keratinocytes, we have recapitulated a highly productive infection of HPV-18 in organotypic epithelial cultures. By using this system, we now report the characterization of four HPV-18 E6 mutations. An E6 null mutant accumulated high levels of p53 and amplified very poorly. p53 siRNA or ectopic WT E6 partially restored amplification, whereas three missense E6 mutations that did not effectively destabilize p53 complemented the null mutant poorly. Unexpectedly, in cis, two of the missense mutants amplified, albeit to a lower extent than the WT and only in cells with undetectable p53. These observations and others implicate p53 and additional host proteins in regulating viral DNA amplification and also suggest an inhibitory effect of E6 overexpression. We show that high levels of viral DNA amplification are critical for late protein expression and report several previously undescribed viral RNAs, including bicistronic transcripts predicted to encode E5 and L2 or an alternative form of E1^E4 and L1. PMID:23572574

  12. Electro-optic modulator with ultra-low residual amplitude modulation for frequency modulation and laser stabilization.

    PubMed

    Tai, Zhaoyang; Yan, Lulu; Zhang, Yanyan; Zhang, Xiaofei; Guo, Wenge; Zhang, Shougang; Jiang, Haifeng

    2016-12-01

    The reduction of the residual amplitude modulation (RAM) induced by electro-optic modulation is essential for many applications of frequency modulation spectroscopy requiring a lower system noise floor. Here, we demonstrate a simple passive approach employing an electro-optic modulator (EOM) cut at Brewster's angle. The proposed EOM exhibits a RAM of a few parts per million, which is comparable with that achieved by a common EOM under critical active temperature and bias voltage controls. The frequency instability of a 10 cm cavity-stabilized laser induced by the RAM effect of the proposed EOM is below 3×10-17 for integration times from 1 to 1000 s, and below 4×10-16 for comprehensive noise contributions for integration times from 1 to 100 s.

  13. Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2.

    PubMed

    Krintel, Christian; Frydenvang, Karla; Olsen, Lars; Kristensen, Maria T; de Barrios, Oriol; Naur, Peter; Francotte, Pierre; Pirotte, Bernard; Gajhede, Michael; Kastrup, Jette S

    2012-01-01

    Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the LBD of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was used. The potent GluA2 modulator BPAM-97 was used as a reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has a Kd of 5.6 μM (ΔH=-4.9 kcal/mol, -TΔS=-2.3 kcal/mol; where 1 kcal≈4.187 kJ). BPAM-97 was used in a displacement assay to determine a Kd of 0.46 mM (ΔH=-1.2 kcal/mol, -TΔS=-3.3 kcal/mol) for the LBD-L483Y-N754S:IDRA-21 complex. The major structural factors increasing the potency of BPAM-97 over IDRA-21 are the increased van der Waals contacts to, primarily, Met496 in GluA2 imposed by the ethyl substituent of BPAM-97. These results add important information on binding affinities and thermodynamic details, and provide a new tool in the development of drugs against cognitive disorders.

  14. Understanding the cell-to-module efficiency gap in Cu(In,Ga)(S,Se)2 photovoltaics scale-up

    NASA Astrophysics Data System (ADS)

    Bermudez, Veronica; Perez-Rodriguez, Alejandro

    2018-06-01

    Cu(In,Ga)(S,Se)2 (CIGS) solar cells show record efficiencies comparable to those of crystalline Si-based technologies. Their industrial module production costs are also comparable to those of Si photovoltaics in spite of their much lower production volume. However, the competitiveness of CIGS is compromised by the difference in performance between cell and module scales, known as the cell-to-module efficiency gap, which is significantly higher than in competing industrial photovoltaic technologies. In this Review, we quantify the main cell-to-module efficiency loss mechanisms and discuss the various strategies explored in academia and industry to reduce the efficiency gap: new transparent conductive oxides, hybrid modularization approaches and the use of wide-bandgap solar absorbers in the 1.4-1.5 eV range. To implement these strategies, research gaps relating to various device layers need to be filled.

  15. Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics

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

    Tocchetti, Guillermo Nicolás

    The multidrug resistance-associated protein 2 (MRP2/ABCC2) is a transporter that belongs to the ATP-binding cassette (ABC) superfamily. In the intestine, it is localized to the apical membrane of the enterocyte and plays a key role in limiting the absorption of xenobiotics incorporated orally. MRP2 may also play a role in systemic clearance of xenobiotics available from the serosal side of the intestine. MRP2 transports a wide range of substrates, mainly organic anions conjugated with glucuronic acid, glutathione and sulfate and its expression can be modulated by xenobiotics at transcriptional- and post-transcriptional levels. Transcriptional regulation is usually mediated by a groupmore » of nuclear receptors. The pregnane X receptor (PXR) is a major member of this group. Relevant drugs described to up-regulate intestinal MRP2 via PXR are rifampicin, spironolactone and carbamazepine, among others. The constitutive androstane receptor (CAR, NR1I3) was also reported to modulate MRP2 expression, phenobarbital being a typical activator. Dietary compounds, including micronutrients and other natural products, are also capable of regulating intestinal MRP2 expression transcriptionally. We have given them particular attention since the composition of the food ingested daily is not necessarily supervised and may result in interactions with therapeutic drugs. Post-transcriptional regulation of MRP2 activity by xenobiotics, e.g. as a consequence of inhibitory actions, is also described in this review. Unfortunately, only few studies report on drug-drug or nutrient-drug interactions as a consequence of modulation of intestinal MRP2 activity by xenobiotics. Future clinical studies are expected to identify additional interactions resulting in changes in efficacy or safety of therapeutic drugs. - Highlights: • Intestinal MRP2 (ABCC2) expression and activity can be regulated by xenobiotics. • PXR and CAR are major MRP2 modulators through a transcriptional mechanism.

  16. Effects of an E-Learning Module on Students' Attitudes in an Electronics Class

    ERIC Educational Resources Information Center

    Getuno, Daniel M.; Kiboss, Joel K.; Changeiywo, Johnson M.; Ogola, Leo B.

    2015-01-01

    Research has shown that students exhibit negative attitudes towards Electronics especially when they are taught using the conventional method. This is in addition to poor instructional methods that do not promote individualization of instruction or make learning interesting. The purpose of this study was to design an e-learning module in…

  17. High-efficiency L-band T/R Module: Development Results

    NASA Technical Reports Server (NTRS)

    Edelstein, Wendy N.; Andricos, Constantine; Wang, Feiyu; Rutled, David B.

    2005-01-01

    Future interferometric synthetic aperture radar (InSAR) systems require electronically scanned phased-array antennas, where the transmit/receive (T/R) module is a key component. The T/R module efficiency is a critical figure of merit and has direct implications on the power dissipation and power generation requirements of the system. Significant improvements in the efficiency of the T/R module will make SAR missions more feasible and affordable. The results of two high-efficiency T/R modules are presented, each based on different power amplifier technologies. One module uses a 30W GaAs Class-AlB power amplifier and the second module uses a 70W LD-MOS Class-ElF power amplifier, where both modules use a common low power section. Each module operates over an 80MHz bandwidth at L-band (1.2GHz) with an overall module efficiency greater than 58%. We will present the results of these two T/R modules that have been designed, built and tested.

  18. Lightweight Trauma Module - LTM

    NASA Technical Reports Server (NTRS)

    Hatfield, Thomas

    2008-01-01

    Current patient movement items (PMI) supporting the military's Critical Care Air Transport Team (CCATT) mission as well as the Crew Health Care System for space (CHeCS) have significant limitations: size, weight, battery duration, and dated clinical technology. The LTM is a small, 20 lb., system integrating diagnostic and therapeutic clinical capabilities along with onboard data management, communication services and automated care algorithms to meet new Aeromedical Evacuation requirements. The Lightweight Trauma Module is an Impact Instrumentation, Inc. project with strong Industry, DoD, NASA, and Academia partnerships aimed at developing the next generation of smart and rugged critical care tools for hazardous environments ranging from the battlefield to space exploration. The LTM is a combination ventilator/critical care monitor/therapeutic system with integrated automatic control systems. Additional capabilities are provided with small external modules.

  19. Critical Success Factors: How One Multinational Company Develops Global E-Learning

    ERIC Educational Resources Information Center

    Nathan, Edward Pavel

    2011-01-01

    This research study examined how a multinational company determined what the critical success factors (CSFs) were for developing global e-learning. The study analyzed how these CSFs were grouped together to make their management more efficient. There were 21 participants in the study who were key stakeholders from the United States, Europe, Latin…

  20. Sulfonamide derivatives of styrylheterocycles as a potent inhibitor of COX-2-mediated prostaglandin E2 production.

    PubMed

    Lim, Chaemin; Lee, Minhee; Park, Eun-Jung; Cho, Ran; Park, Hyen-Joo; Lee, Seong Jin; Cho, Heeyeong; Lee, Sang Kook; Kim, Sanghee

    2010-12-01

    The overproduction of prostaglandin E(2) (PGE(2)) plays an important role in a variety of pathophysiological processes including inflammation and carcinogenesis. Therefore, the modulation of PGE(2) production is a promising target in the design of chemotherapeutic agents. In the present study, the inhibitory effects of a series of styrylheterocycles having either a p-SO(2)NH(2) or p-SO(2)Me group on the production of cyclooxygenase-2-mediated PGE(2) were evaluated in lipopolysaccharide-stimulated RAW264.7 murine macrophages. Among the series of styrylheterocycle derivatives, (E)-4-(2-(thiophen-3-yl)vinyl)benzenesulfonamide exhibited a potent inhibitory activity, with an IC(50) value of 0.013 μM. The inhibitory activity against the overproduction of PGE(2) by the active compound was found to be due in part to the suppression of COX-2 mRNA expression. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Aquatic modules for bioregenerative life support systems: developmental aspects based on the space flight results of the C.E.B.A.S. MIN-MODULE.

    PubMed

    Blum, V

    2003-01-01

    The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) is an artificial aquatic ecosystem which contains teleost fishes, water snails, ammonia oxidizing bacteria and edible non-gravitropic water plants. It serves as a model for aquatic food production modules which are not seriously affected by microgravity and other space conditions. Its space flight version, the so-called C.E.B.A.S. MINI-MODULE was already successfully tested in the STS-89 and STS-90 (NEUROLAB) missions. It will be flown a third time in space with the STS-107 mission in January 2003. All results obtained so far in space indicate that the basic concept of the system is more than suitable to drive forward its development. The C.E.B.A.S. MINI-MODULE is located within a middeck locker with limited space for additional components. These technical limitations allow only some modifications which lead to a maximum experiment time span of 120 days which is not long enough for scientifically essential multi-generation-experiments. The first necessary step is the development of "harvesting devices" for the different organisms. In the limited space of the plant bioreactor a high biomass production leads to self-shadowing effects which results in an uncontrolled degradation and increased oxygen consumption by microorganisms which will endanger the fishes and snails. It was shown already that the latter reproduce excellently in space and that the reproductive functions of the fish species are not affected. Although the parent-offspring-cannibalism of the ovoviviparous fish species (Xiphophorus helleri) serves as a regulating factor in population dynamics an uncontrolled snail reproduction will also induce an increased oxygen consumption per se and a high ammonia concentration in the water. If harvesting locks can be handled by astronauts in, e. g., 4-week intervals their construction is not very difficult and basic technical solutions are already developed. The second problem is the feeding of the

  2. What happens in the lab does not stay in the lab [corrected]: Applying midstream modulation to enhance critical reflection in the laboratory.

    PubMed

    Schuurbiers, Daan

    2011-12-01

    In response to widespread policy prescriptions for responsible innovation, social scientists and engineering ethicists, among others, have sought to engage natural scientists and engineers at the 'midstream': building interdisciplinary collaborations to integrate social and ethical considerations with research and development processes. Two 'laboratory engagement studies' have explored how applying the framework of midstream modulation could enhance the reflections of natural scientists on the socio-ethical context of their work. The results of these interdisciplinary collaborations confirm the utility of midstream modulation in encouraging both first- and second-order reflective learning. The potential for second-order reflective learning, in which underlying value systems become the object of reflection, is particularly significant with respect to addressing social responsibility in research practices. Midstream modulation served to render the socio-ethical context of research visible in the laboratory and helped enable research participants to more critically reflect on this broader context. While lab-based collaborations would benefit from being carried out in concert with activities at institutional and policy levels, midstream modulation could prove a valuable asset in the toolbox of interdisciplinary methods aimed at responsible innovation.

  3. SMED-TLX-1 (NR2E1) is critical for tissue and body plan maintenance in Schmidtea mediterranea in fasting/feeding cycles.

    PubMed

    Raška, O; Kostrouchová, V; Behenský, F; Yilma, P; Saudek, V; Kostrouch, Z; Kostrouchová, M

    2011-01-01

    Nuclear receptors (NRs), or nuclear hormone receptors (NHRs), are transcription factors that regulate development and metabolism of most if not all animal species. Their regulatory networks include conserved mechanisms that are shared in-between species as well as mechanisms that are restricted to certain phyla or even species. In search for conserved members of the NHR family in Schmidtea mediterranea, we identified a molecular signature of a class of NRs, NR2E1, in the S. mediterranea genome and cloned its complete cDNA coding sequence. The derived amino acid sequence shows a high degree of conservation of both DNA-binding domain and ligand- binding domain and a remarkably high homology to vertebrate NR2E1 and C. elegans NHR-67. Quantitative PCR detected approximately ten-fold higher expression of Smed-tlx-1 in the proximal part of the head compared to the tail region. The expression of Smed-tlx-1 is higher during fed state than during fasting. Smed-tlx-1 down-regulation by RNA interference affects the ability of the animals to maintain body plan and induces defects of brain, eyes and body shape during fasting and re-growing cycles. These results suggest that SMED-TLX-1 is critical for tissue and body plan maintenance in planaria.

  4. Critical Success Factors: How One Multinational Company Develops Global E-Learning

    ERIC Educational Resources Information Center

    Nathan, Edward Pavel

    2009-01-01

    This research study examined how a multinational company determined what the critical success factors (CSFs) were for developing global e-learning. The study analyzed how these CSFs were grouped together in order to make their management more efficient. There were 21 participants in the study who were key stakeholders and came from one of four…

  5. MoS2 Heterojunctions by Thickness Modulation

    PubMed Central

    Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; Ko, Changhyun; Seuk Kang, Jeong; Lien, Der-Hsien; Najmzadeh, Mohammad; Tongay, Sefaattin; Wu, Junqiao; Javey, Ali

    2015-01-01

    In this work, we report lateral heterojunction formation in as-exfoliated MoS2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. The work presents experimental and theoretical understanding of the band alignment and photoresponse of thickness modulated MoS2 junctions with important implications for exploring novel optoelectronic devices. PMID:26121940

  6. Folic acid modulates eNOS activity via effects on posttranslational modifications and protein–protein interactions☆

    PubMed Central

    Taylor, Sarah Y.; Dixon, Hannah M.; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

    2013-01-01

    Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein–protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment. PMID:23796957

  7. Promotion of critical thinking in e-learning: a qualitative study on the experiences of instructors and students

    PubMed Central

    Gharib, Mitra; Zolfaghari, Mitra; Mojtahedzadeh, Rita; Mohammadi, Aeen; Gharib, Atoosa

    2016-01-01

    Background With the increasing popularity of e-learning programs, educational stakeholders are attempting to promote critical thinking in the virtual education system. This study aimed to explore the experiences of both the instructors and the students about critical thinking promotion within the virtual education system. Methods This qualitative study recruited the instructors and students from four academic disciplines provided by the Virtual School of Tehran University of Medical Sciences (Tehran, Iran). All programs were master’s degree programs and utilized a blended (combination of e-learning and face to face) training. Semistructured interviews with the participants were used to collect data. Results The participants had a variety of experiences about how to promote critical thinking. These experiences were conceptualized in four main themes, namely, instructional design, educational leadership and management, local evidence, and belief systems. Conclusion The present study clarified the factors affecting critical thinking promotion in e-learning. Not only the instructors but also the educational designers and leaders can benefit from our findings to improve the quality of virtual education programs and promote critical thinking. PMID:27217807

  8. Promotion of critical thinking in e-learning: a qualitative study on the experiences of instructors and students.

    PubMed

    Gharib, Mitra; Zolfaghari, Mitra; Mojtahedzadeh, Rita; Mohammadi, Aeen; Gharib, Atoosa

    2016-01-01

    With the increasing popularity of e-learning programs, educational stakeholders are attempting to promote critical thinking in the virtual education system. This study aimed to explore the experiences of both the instructors and the students about critical thinking promotion within the virtual education system. This qualitative study recruited the instructors and students from four academic disciplines provided by the Virtual School of Tehran University of Medical Sciences (Tehran, Iran). All programs were master's degree programs and utilized a blended (combination of e-learning and face to face) training. Semistructured interviews with the participants were used to collect data. The participants had a variety of experiences about how to promote critical thinking. These experiences were conceptualized in four main themes, namely, instructional design, educational leadership and management, local evidence, and belief systems. The present study clarified the factors affecting critical thinking promotion in e-learning. Not only the instructors but also the educational designers and leaders can benefit from our findings to improve the quality of virtual education programs and promote critical thinking.

  9. Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation

    PubMed Central

    Timm, David E.; Benveniste, Morris; Weeks, Autumn M.; Nisenbaum, Eric S.

    2011-01-01

    At the dimer interface of the extracellular ligand-binding domain of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors a hydrophilic pocket is formed that is known to interact with two classes of positive allosteric modulators, represented by cyclothiazide and the ampakine 2H,3H,6aH-pyrrolidino(2,1–3′,2′)1,3-oxazino(6′,5′-5,4)benzo(e)1,4-dioxan-10-one (CX614). Here, we present structural and functional data on two new positive allosteric modulators of AMPA receptors, phenyl-1,4-bis-alkylsulfonamide (CMPDA) and phenyl-1,4-bis-carboxythiophene (CMPDB). Crystallographic data show that these compounds bind within the modulator-binding pocket and that substituents of each compound overlap with distinct moieties of cyclothiazide and CX614. The goals of the present study were to determine 1) the degree of modulation by CMPDA and CMPDB of AMPA receptor deactivation and desensitization; 2) whether these compounds are splice isoform-selective; and 3) whether predictions of mechanism of action could be inferred by comparing molecular interactions between the ligand-binding domain and each compound with those of cyclothiazide and CX614. CMPDB was found to be more isoform-selective than would be predicted from initial binding assays. It is noteworthy that these new compounds are both more potent and more effective and may be more clinically relevant than the AMPA receptor modulators described previously. PMID:21543522

  10. Superconductivity with extremely large upper critical fields in Nb2Pd0.81S5

    PubMed Central

    Zhang, Q.; Li, G.; Rhodes, D.; Kiswandhi, A.; Besara, T.; Zeng, B.; Sun, J.; Siegrist, T.; Johannes, M. D.; Balicas, L.

    2013-01-01

    Here, we report the discovery of superconductivity in a new transition metal-chalcogenide compound, i.e. Nb2Pd0.81S5, with a transition temperature Tc ≅ 6.6 K. Despite its relatively low Tc, it displays remarkably high and anisotropic superconducting upper critical fields, e.g. μ0Hc2 (T → 0 K) > 37 T for fields applied along the crystallographic b-axis. For a field applied perpendicularly to the b-axis, μ0Hc2 shows a linear dependence in temperature which coupled to a temperature-dependent anisotropy of the upper critical fields, suggests that Nb2Pd0.81S5 is a multi-band superconductor. This is consistent with band structure calculations which reveal nearly cylindrical and quasi-one-dimensional Fermi surface sheets having hole and electron character, respectively. The static spin susceptibility as calculated through the random phase approximation, reveals strong peaks suggesting proximity to a magnetic state and therefore the possibility of unconventional superconductivity. PMID:23486091

  11. Extreme and superextreme events in a loss-modulated CO2 laser: Nonlinear resonance route and precursors

    NASA Astrophysics Data System (ADS)

    Bonatto, Cristian; Endler, Antonio

    2017-07-01

    We investigate the occurrence of extreme and rare events, i.e., giant and rare light pulses, in a periodically modulated CO2 laser model. Due to nonlinear resonant processes, we show a scenario of interaction between chaotic bands of different orders, which may lead to the formation of extreme and rare events. We identify a crisis line in the modulation parameter space, and we show that, when the modulation amplitude increases, remaining in the vicinity of the crisis, some statistical properties of the laser pulses, such as the average and dispersion of amplitudes, do not change much, whereas the amplitude of extreme events grows enormously, giving rise to extreme events with much larger deviations than usually reported, with a significant probability of occurrence, i.e., with a long-tailed non-Gaussian distribution. We identify recurrent regular patterns, i.e., precursors, that anticipate the emergence of extreme and rare events, and we associate these regular patterns with unstable periodic orbits embedded in a chaotic attractor. We show that the precursors may or may not lead to the emergence of extreme events. Thus, we compute the probability of success or failure (false alarm) in the prediction of the extreme events, once a precursor is identified in the deterministic time series. We show that this probability depends on the accuracy with which the precursor is identified in the laser intensity time series.

  12. SU-E-T-97: Dependence Of Optically Stimulated Luminescent Dosimeter (OSLD) Out Of Field Response On Volumetric Modulated Arc Therapy (VMAT) Field Modulation

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

    Ware, S; Clouser, E

    2014-06-01

    Purpose: To determine the out of field response of Microstar ii OSLDs as a function of field modulation and distance in VMAT plan delivery. This work has potential application in fetal dose monitoring or measurements on cardiac pacemakers Methods: VMAT plans were created in Eclipse and optimized to varying degrees of modulation. Three plans were chosen to represent low, medium and high degrees of modulation (modulation factors as defined by MU/cGy). Plans were delivered to slabs of solid water with dimensions 60cm length, 30cm width, and 10cm height. For each modulation factor, 2 OSLDs were placed at 1cm depth withmore » out of field distances of 1, 2, 3, 5, 8 and 10cm and the plan delivered isocentrically to a depth of 5cm. This technique was repeated for a Farmer Chamber by incrementing the table by the appropriate distance. The charge readings for the Farmer Chamber were converted to dose and the ratios taken as functions of modulation factors and distances out of field Results: Examination of the results as a function of out of field distance shows a trend of increasing OSLD/Farmer Chamber ratios for all modulation factors. The slopes appear to be roughly equivalent for all modulation factors investigated. Results as a function of modulation showed a downward trend for all out of field distances, with the greatest differences seen at 5cm and 8cm Conclusion: This study demonstrates that the response of OSLD dosimeters change as a function of out of field distance and modulation. The differences seen are within the stated accuracy of the system for the out of field distances and modulations investigated. Additional investigation is warranted to see if the OSLD response changes appreciably with longer out of field distances or wider ranges of modulation.« less

  13. Student Responses to an ICT-Based E-Assessment Application for the Teaching Practicum/Teaching Practice MODULE

    ERIC Educational Resources Information Center

    Davids, M. Noor

    2017-01-01

    Situated within the context of Initial Teacher Education (ITE) in South Africa, this study introduces the notion of an interactive Teaching Practicum E- Assessment application: e-assessment application for the teaching practicum/Teaching Practice module to replace the current model of assessment. At present students enrolled for an Initial Teacher…

  14. C-Terminal carbohydrate-binding module 9_2 fused to the N-terminus of GH11 xylanase from Aspergillus niger.

    PubMed

    Xu, Wenxuan; Liu, Yajuan; Ye, Yanxin; Liu, Meng; Han, Laichuang; Song, Andong; Liu, Liangwei

    2016-10-01

    The 9_2 carbohydrate-binding module (C2) locates natively at the C-terminus of the GH10 thermophilic xylanase from Thermotoga marimita. When fused to the C-terminus, C2 improved thermostability of a GH11 xylanase (Xyn) from Aspergillus niger. However, a question is whether the C-terminal C2 would have a thermostabilizing effect when fused to the N-terminus of a catalytic module. A chimeric enzyme, C2-Xyn, was created by step-extension PCR, cloned in pET21a(+), and expressed in E. coli BL21(DE3). The C2-Xyn exhibited a 2 °C higher optimal temperature, a 2.8-fold longer thermostability, and a 4.5-fold higher catalytic efficiency on beechwood xylan than the Xyn. The C2-Xyn exhibited a similar affinity for binding to beechwood xylan and a higher affinity for oat-spelt xylan than Xyn. C2 is a thermostabilizing carbohydrate-binding module and provides a model of fusion at an enzymatic terminus inconsistent with the modular natural terminal location.

  15. Strain-induced dimensionality crossover of precursor modulations in Ni2MnGa

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

    Nie, Zhihua; Wang, Yandong; Shang, Shunli

    2015-01-01

    Precursor modulations often occur in functional materials like magnetic shape memory alloys, ferroelectrics, and superconductors. In this letter, we have revealed the underlying mechanism of the precursor modulations in ferromagnetic shape memory alloys Ni2MnGa by combining synchrotron-based x-ray diffraction experiments and first-principles phonon calculations. We discovered the precursor modulations along [011] direction can be eliminated with [001] uniaxial loading, while the precursor modulations or premartensite can be totally suppressed by hydrostatic pressure condition. The TA2 phonon anomaly is sensitive to stress induced lattice strain, and the entire TA2 branch is stabilized along the directions where precursor modulations are eliminated bymore » external stress. Our discovery bridges precursor modulations and phonon anomalies, and sheds light on the microscopic mechanism of the two-step superelasticity in precursor martensite.« less

  16. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    PubMed Central

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  17. Trends in free WWW-based E-learning Modules seen from the Learning Resource Server Medicine (LRSMed).

    PubMed

    Stausberg, Jürgen; Geueke, Martin; Bludßat, Kevin

    2005-01-01

    Despite the lost enthusiasm concerning E-learning a lot of material is available on the World Wide Web (WWW) free of charge. This material is collected and systematically described by services like the Learning Resource Server Medicine (LRSMed) at http://mmedia.medizin.uni-essen.de/portal/. With the LRSMed E-learning modules are made available for medical students by means of a metadata description that can be used for a catalogue search. The number of resources included has risen enormously from 100 in 1999 up to 805 today. Especially in 2004 there was an exponential increase in the LRSMed's content. Anatomy is still the field with the highest amount of available material, but general medicine has improved its position over the years and is now the second one. Technically and didactically simple material as scripts, textbooks, and link lists (called info services) is still dominating. Similar to 1999, there is not one module which could be truly referred to as tutorial dialogue. Simple material can not replace face-to-face-teaching. But it could be combined with conventional courses to establish some kind of blending learning. The scene of free E-learning modules on the WWW is ready to meet current challenges for efficient training of students and continuing education in medicine.

  18. Engineering vaccines and niches for immune modulation.

    PubMed

    Purwada, Alberto; Roy, Krishnendu; Singh, Ankur

    2014-04-01

    Controlled modulation of immune response, especially the balance between immunostimulatory and immunosuppressive responses, is critical for a variety of clinical applications, including immunotherapies against cancer and infectious diseases, treatment of autoimmune disorders, transplant surgeries, regenerative medicine, prosthetic implants, etc. Our ability to precisely modify both innate and adaptive immune responses could provide new therapeutic directions in a variety of diseases. In the context of vaccines and immunotherapies, the interplay between antigen-presenting cells (e.g. dendritic cells and macrophages), B cells, T helper and killer subtypes, and regulatory T- and B-cell responses is critical for generating effective immunity against cancer, infectious diseases and autoimmune diseases. In recent years, immunoengineering has emerged as a new field that uses quantitative engineering tools to understand molecular-, cellular- and system-level interactions of the immune system and to develop design-driven approaches to control and modulate immune responses. Biomaterials are an integral part of this engineering toolbox and can exploit the intrinsic biological and mechanical cues of the immune system to directly modulate and train immune cells and direct their response to a particular phenotype. A large body of literature exists on strategies to evade or suppress the immune response in implants, transplantation and regenerative medicine. This review specifically focuses on the use of biomaterials for immunostimulation and controlled modulation, especially in the context of vaccines and immunotherapies against cancer, infectious diseases and autoimmune disorders. Bioengineering smart systems that can simultaneously deliver multiple bioactive agents in a controlled manner or can work as a niche for in situ priming and modulation of the immune system could significantly enhance the efficacy of next-generation immunotherapeutics. In this review, we describe our

  19. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells.

    PubMed

    Leung, Travis; Rajendran, Ramkumar; Singh, Subir; Garva, Richa; Krstic-Demonacos, Marija; Demonacos, Constantinos

    2013-11-08

    progression, and metastasis, of advanced stages of breast cancer can be modulated by induction of CYP2E1 activity.

  20. Intermediate load modules for test and evaluation

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Photovoltaic modules were tested for qualification. Tests involved the following: (1) delivery of 20 solar cells for use as reference cells; (2) module documentation and inspection plans specifying the 10 Group I modules; (3) design review of module documentation from Group I modules; (4) revise module documentation to overcome any problems of deficiencies associated with the Group I modules; (5) delivery of 10 Group II modules built to revised specifications; (6) testing of Group II modules to the criteria as outlined in qualification specification. It is found that the solarvolt MSP43E40B satisfies the design criteria of qualification specification for intermediate load modules. Design changes were made in the Group I modules to overcome the deficiencies which allowed Group II modules to pass the qualification tests.

  1. Structures of (2E,5E)-2-(4-cyanobenzylidene)-5-(4-dimethylaminobenzylidene)cyclopentanone and (2E,5E)-2-benzylidene-5-cinnamylidenecyclopentanone

    NASA Astrophysics Data System (ADS)

    Zoto, Christopher A.; MacDonald, John C.

    2017-10-01

    The X-ray crystal structures of (2E,5E)-2-(4-cyanobenzylidene)-5-(4-dimethylaminobenzylidene)cyclopentanone (I) and (2E,5E)-2-benzylidene-5-cinnamylidenecyclopentanone (II) are presented, compared to the gas phase structures calculated using density functional theory, and discussed in the context of the photophysical behavior exhibited by I and II. Compound I crystallizes in the triclinic space group P 1 bar with a = 6.8743(2) Å, b = 8.8115(2) Å, c = 14.9664(4) Å, α = 77.135(2)°, β = 81.351(2)°, γ = 80.975(2)°, and Z = 2, and exhibits a planar structure. Compound II crystallizes in the monoclinic space group C2/c with a = 33.4281(10) Å, b = 11.9668(4) Å, c = 7.8031(2) Å, β = 92.785(2)°, and Z = 8, and adopts a nonplanar structure in the solid state and calculated structure.

  2. Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.

    PubMed

    Mittal, Rahul; Debs, Luca H; Patel, Amit P; Nguyen, Desiree; Patel, Kunal; O'Connor, Gregory; Grati, M'hamed; Mittal, Jeenu; Yan, Denise; Eshraghi, Adrien A; Deo, Sapna K; Daunert, Sylvia; Liu, Xue Zhong

    2017-09-01

    Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. The marginal fit of E.max Press and E.max CAD lithium disilicate restorations: A critical review.

    PubMed

    Mounajjed, Radek; M Layton, Danielle; Azar, Basel

    2016-12-01

    This critical review aimed to assess the vertical marginal gap that was present when E.max lithium disilicate-based restoration (Press and CAD) are fabricated in-vitro. Published articles reporting vertical marginal gap measurements of in-vitro restorations that had been fabricated from E.Max lithium disilicate were sought with an electronic search of MEDLINE (PubMed) and hand search of selected dental journals. The outcomes were reviewed qualitatively. The majority of studies that compared the marginal fit of E.max press and E.max CAD restorations, found that the E.max lithium disilicate restorations fabricated with the press technique had significantly smaller marginal gaps than those fabricated with CAD technique. This research indicates that E.max lithium disilicate restorations fabricated with the press technique have measurably smaller marginal gaps when compared with those fabricated with CAD techniques within in-vitro environments. The marginal gaps achieved by the restorations across all groups were within a clinically acceptable range.

  4. Critical gases for critical issues: CO2 technologies for oral drug delivery.

    PubMed

    Danan, Hana; Esposito, Pierandrea

    2014-02-01

    In recent years, CO2-based technologies have gained considerable interest in the pharmaceutical industry for their potential applications in drug formulation and drug delivery. The exploitation of peculiar properties of gases under supercritical conditions has been studied in the last 20 years with mixed results. Promising drug-delivery technologies, based on supercritical CO2, have mostly failed when facing challenges of industrial scaleability and economical viability. Nevertheless, a 'second generation' of processes, based on CO2 around and below critical point has been developed, possibly offering technology-based solutions to some of the current issues of pharmaceutical development. In this review, we highlight the most recent advancements in this field, with a particular focus on the potential of CO2-based technologies in addressing critical issues in oral delivery, and briefly discuss the future perspectives of dense CO2-assisted processes as enabling technologies in drug delivery.

  5. Content validity of critical success factors for e-Government implementation in Indonesia

    NASA Astrophysics Data System (ADS)

    Napitupulu, D.; Syafrullah, M.; Rahim, R.; Amar, A.; Sucahyo, YG

    2018-05-01

    The purpose of this research is to validate the Critical Success Factors (CSFs) of e-Government implementation in Indonesia. The e-Government initiative conducted only to obey the regulation but ignoring the quality. Defining CSFs will help government agencies to avoid failure of e-Government projects. A survey with the questionnaire was used to validate the item of CSF based on expert judgment through two round of Delphi. The result showed from 67 subjects in instrument tested; there are 11 invalid items deleted and remain only 56 items that had good content validity and internal reliability. Therefore, all 56 CSFs should be adopted by government agencies in Indonesia to support e-Government implementation.

  6. MoS 2 Heterojunctions by Thickness Modulation

    DOE PAGES

    Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; ...

    2015-06-30

    In this work, we report lateral heterojunction formation in as-exfoliated MoS 2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. Finally, the work presents experimental and theoretical understanding of the band alignmentmore » and photoresponse of thickness modulated MoS 2 junctions with important implications for exploring novel optoelectronic devices.« less

  7. Coherent-Anomaly Method in Critical Phenomena. III. Mean-Field Transfer-Matrix Method in the 2D Ising Model

    NASA Astrophysics Data System (ADS)

    Hu, Xiao; Katori, Makoto; Suzuki, Masuo

    1987-11-01

    Two kinds of systematic mean-field transfer-matrix methods are formulated in the 2-dimensional Ising spin system, by introducing Weiss-like and Bethe-like approximations. All the critical exponents as well as the true critical point can be estimated in these methods following the CAM procedure. The numerical results of the above system are Tc*≃2.271 (J/kB), γ{=}γ'≃1.749, β≃0.131 and δ≃15.1. The specific heat is confirmd to be continuous and to have a logarithmic divergence at the true critical point, i.e., α{=}α'{=}0. Thus, the finite-degree-of-approximation scaling ansatz is shown to be correct and very powerful in practical estimations of the critical exponents as well as the true critical point.

  8. Social closeness and feedback modulate susceptibility to the framing effect.

    PubMed

    Sip, Kamila E; Smith, David V; Porcelli, Anthony J; Kar, Kohitij; Delgado, Mauricio R

    2015-01-01

    Although we often seek social feedback (SFB) from others to help us make decisions, little is known about how SFB affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision-making is modulated by SFB valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity to keep (gain frame) or lose (loss frame) part of an initial endowment. Periodically, participants were provided with positive (e.g., "Nice!") or negative (e.g., "Lame!") feedback about their choices. Such feedback was provided by either a confederate (Experiment 1) or a gender-matched close friend (Experiment 2). As expected, the framing effect was observed in both experiments. Critically, an individual's susceptibility to the framing effect was modulated by the valence of the SFB, but only when the feedback provider was a close friend. This effect was reflected in the activation patterns of ventromedial prefrontal cortex and posterior cingulate cortex, regions involved in complex decision-making. Taken together, these results highlight social closeness as an important factor in understanding the impact of SFB on neural mechanisms of decision-making.

  9. Social closeness and feedback modulate susceptibility to the framing effect

    PubMed Central

    Sip, Kamila E.; Smith, David V.; Porcelli, Anthony J.; Kar, Kohitij; Delgado, Mauricio R.

    2014-01-01

    Although, we often seek social feedback from others to help us make decisions, little is known about how social feedback affects decisions under risk, particularly from a close peer. We conducted two experiments using an established framing task to probe how decision making is modulated by social feedback valence (positive, negative) and the level of closeness with feedback provider (friend, confederate). Participants faced mathematically equivalent decisions framed as either an opportunity to keep (gain frame) or lose (loss frame) part of an initial endowment. Periodically, participants were provided with positive (e.g., “Nice!”) or negative (e.g., “Lame!”) feedback about their choices. Such feedback was provided by either a confederate (Experiment 1), or a gender-matched close friend (Experiment 2). As expected, the framing effect was observed in both experiments. Critically, an individual’s susceptibility to the framing effect was modulated by the valence of the social feedback, but only when the feedback provider was a close friend. This effect was reflected in the activation patterns of ventromedial prefrontal cortex and posterior cingulate cortex, regions involved in complex decision making. Taken together, these results highlight social closeness as an important factor in understanding the impact of social feedback on neural mechanisms of decision making. PMID:25074501

  10. Engineering Surface Critical Behavior of (2 +1 )-Dimensional O(3) Quantum Critical Points

    NASA Astrophysics Data System (ADS)

    Ding, Chengxiang; Zhang, Long; Guo, Wenan

    2018-06-01

    Surface critical behavior (SCB) refers to the singularities of physical quantities on the surface at the bulk phase transition. It is closely related to and even richer than the bulk critical behavior. In this work, we show that three types of SCB universality are realized in the dimerized Heisenberg models at the (2 +1 )-dimensional O(3) quantum critical points by engineering the surface configurations. The ordinary transition happens if the surface is gapped in the bulk disordered phase, while the gapless surface state generally leads to the multicritical special transition, even though the latter is precluded in classical phase transitions because the surface is in the lower critical dimension. An extraordinary transition is induced by the ferrimagnetic order on the surface of the staggered Heisenberg model, in which the surface critical exponents violate the results of the scaling theory and thus seriously challenge our current understanding of extraordinary transitions.

  11. Safety Criticality Standards Using the French CRISTAL Code Package: Application to the AREVA NP UO{sub 2} Fuel Fabrication Plant

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

    Doucet, M.; Durant Terrasson, L.; Mouton, J.

    2006-07-01

    Criticality safety evaluations implement requirements to proof of sufficient sub critical margins outside of the reactor environment for example in fuel fabrication plants. Basic criticality data (i.e., criticality standards) are used in the determination of sub critical margins for all processes involving plutonium or enriched uranium. There are several criticality international standards, e.g., ARH-600, which is one the US nuclear industry relies on. The French Nuclear Safety Authority (DGSNR and its advising body IRSN) has requested AREVA NP to review the criticality standards used for the evaluation of its Low Enriched Uranium fuel fabrication plants with CRISTAL V0, the recentlymore » updated French criticality evaluation package. Criticality safety is a concern for every phase of the fabrication process including UF{sub 6} cylinder storage, UF{sub 6}-UO{sub 2} conversion, powder storage, pelletizing, rod loading, assembly fabrication, and assembly transportation. Until 2003, the accepted criticality standards were based on the French CEA work performed in the late seventies with the APOLLO1 cell/assembly computer code. APOLLO1 is a spectral code, used for evaluating the basic characteristics of fuel assemblies for reactor physics applications, which has been enhanced to perform criticality safety calculations. Throughout the years, CRISTAL, starting with APOLLO1 and MORET 3 (a 3D Monte Carlo code), has been improved to account for the growth of its qualification database and for increasing user requirements. Today, CRISTAL V0 is an up-to-date computational tool incorporating a modern basic microscopic cross section set based on JEF2.2 and the comprehensive APOLLO2 and MORET 4 codes. APOLLO2 is well suited for criticality standards calculations as it includes a sophisticated self shielding approach, a P{sub ij} flux determination, and a 1D transport (S{sub n}) process. CRISTAL V0 is the result of more than five years of development work focusing on

  12. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    PubMed

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  13. Space Qualification Test of a-Silicon Solar Cell Modules

    NASA Technical Reports Server (NTRS)

    Kim, Q.; Lawton, R. A.; Manion, S. J.; Okuno, J. O.; Ruiz, R. P.; Vu, D. T.; Vu, D. T.; Kayali, S. A.; Jeffrey, F. R.

    2004-01-01

    The basic requirements of solar cell modules for space applications are generally described in MIL-S-83576 for the specific needs of the USAF. However, the specifications of solar cells intended for use on space terrestrial applications are not well defined. Therefore, this qualifications test effort was concentrated on critical areas specific to the microseismometer probe which is intended to be included in the Mars microprobe programs. Parameters that were evaluated included performance dependence on: illuminating angles, terrestrial temperatures, lifetime, as well as impact landing conditions. Our qualification efforts were limited to these most critical areas of concern. Most of the tested solar cell modules have met the requirements of the program except the impact tests. Surprisingly, one of the two single PIN 2 x 1 amorphous solar cell modules continued to function even after the 80000G impact tests. The output power parameters, Pout, FF, Isc and Voc, of the single PIN amorphous solar cell module were found to be 3.14 mW, 0.40, 9.98 mA and 0.78 V, respectively. These parameters are good enough to consider the solar module as a possible power source for the microprobe seismometer. Some recommendations were made to improve the usefulness of the amorphous silicon solar cell modules in space terrestrial applications, based on the results obtained from the intensive short term lab test effort.

  14. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

    PubMed

    Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

    2017-03-07

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

  15. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons

    PubMed Central

    Ali, Yousuf O.; Bradley, Gillian; Lu, Hui-Chen

    2017-01-01

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons. PMID:28266613

  16. Purification and Characterization of Tagless Recombinant Human Elongation Factor 2 Kinase (eEF-2K) Expressed in Escherichia coli

    PubMed Central

    Abramczyk, Olga; Tavares, Clint D. J.; Devkota, Ashwini K.; Ryazanov, Alexey G.; Turk, Benjamin E.; Riggs, Austen F.; Ozpolat, Bulent; Dalby, Kevin N.

    2012-01-01

    The eukaryotic elongation factor 2 kinase (eEF-2K) modulates the rate of protein synthesis by impeding the elongation phase of translation by inactivating the eukaryotic elongation factor 2 (eEF-2) via phosphorylation. eEF-2K is known to be activated by calcium and calmodulin, whereas the mTOR and MAPK pathways are suggested to negatively regulate kinase activity. Despite its pivotal role in translation regulation and potential role in tumor survival, the structure, function and regulation of eEF-2K have not been described in detail. This deficiency may result from the difficulty of obtaining the recombinant kinase in a form suitable for biochemical analysis. Here we report the purification and characterization of recombinant human eEF-2K expressed in the Escherichia coli strain Rosetta-gami 2(DE3). Successive chromatography steps utilizing Ni-NTA affinity, anion-exchange and gel filtration columns accomplished purification. Cleavage of the thioredoxin-His6-tag from the N-terminus of the expressed kinase with TEV protease yielded 9 mg of recombinant (G-D-I)-eEF-2K per liter of culture. Light scattering shows that eEF-2K is a monomer of ~ 85 kDa. In vitro kinetic analysis confirmed that recombinant human eEF-2K is able to phosphorylate wheat germ eEF-2 with kinetic parameters comparable to the mammalian enzyme. PMID:21605678

  17. Studying fission neutrons with 2E-2v and 2E

    NASA Astrophysics Data System (ADS)

    Al-Adili, Ali; Jansson, Kaj; Tarrío, Diego; Hambsch, Franz-Josef; Göök, Alf; Oberstedt, Stephan; Olivier Frégeau, Marc; Gustavsson, Cecilia; Lantz, Mattias; Mattera, Andrea; Prokofiev, Alexander V.; Rakopoulos, Vasileios; Solders, Andreas; Vidali, Marzio; Österlund, Michael; Pomp, Stephan

    2018-03-01

    This work aims at measuring prompt-fission neutrons at different excitation energies of the nucleus. Two independent techniques, the 2E-2v and the 2E techniques, are used to map the characteristics of the mass-dependent prompt fission neutron multiplicity, v(A), when the excitation energy is increased. The VERDI 2E-2v spectrometer is being developed at JRC-GEEL. The Fission Fragment (FF) energies are measured using two arrays of 16 silicon (Si) detectors each. The FFs velocities are obtained by time-of-flight, measured between micro-channel plates (MCP) and Si detectors. With MCPs placed on both sides of the fission source, VERDI allows for independent timing measurements for both fragments. 252Cf(sf) was measured and the present results revealed particular features of the 2E-2v technique. Dedicated simulations were also performed using the GEF code to study important aspects of the 2E-2v technique. Our simulations show that prompt neutron emission has a non-negligible impact on the deduced fragment data and affects also the shape of v(A). Geometrical constraints lead to a total-kinetic energy-dependent detection efficiency. The 2E technique utilizes an ionization chamber together with two liquid scintillator detectors. Two measurements have been performed, one of 252Cf(sf) and another one of thermal-neutron induced fission in 235U(n,f). Results from 252Cf(sf) are reported here.

  18. Stratified charge rotary engine critical technology enablement. Volume 2: Appendixes

    NASA Technical Reports Server (NTRS)

    Irion, C. E.; Mount, R. E.

    1992-01-01

    This second volume of appendixes is a companion to Volume 1 of this report which summarizes results of a critical technology enablement effort with the stratified charge rotary engine (SCRE) focusing on a power section of 0.67 liters (40 cu. in.) per rotor in single and two rotor versions. The work is a continuation of prior NASA Contracts NAS3-23056 and NAS3-24628. Technical objectives are multi-fuel capability, including civil and military jet fuel and DF-2, fuel efficiency of 0.355 Lbs/BHP-Hr. at best cruise condition above 50 percent power, altitude capability of up to 10Km (33,000 ft.) cruise, 2000 hour TBO and reduced coolant heat rejection. Critical technologies for SCRE's that have the potential for competitive performance and cost in a representative light-aircraft environment were examined. Objectives were: the development and utilization of advanced analytical tools, i.e. higher speed and enhanced three dimensional combustion modeling; identification of critical technologies; development of improved instrumentation; and to isolate and quantitatively identify the contribution to performance and efficiency of critical components or subsystems. A family of four-stage third-order explicit Runge-Kutta schemes is derived that required only two locations and has desirable stability characteristics. Error control is achieved by embedding a second-order scheme within the four-stage procedure. Certain schemes are identified that are as efficient and accurate as conventional embedded schemes of comparable order and require fewer storage locations.

  19. Modulation/demodulation techniques for satellite communications. Part 2: Advanced techniques. The linear channel

    NASA Technical Reports Server (NTRS)

    Omura, J. K.; Simon, M. K.

    1982-01-01

    A theory is presented for deducing and predicting the performance of transmitter/receivers for bandwidth efficient modulations suitable for use on the linear satellite channel. The underlying principle used is the development of receiver structures based on the maximum-likelihood decision rule. The application of the performance prediction tools, e.g., channel cutoff rate and bit error probability transfer function bounds to these modulation/demodulation techniques.

  20. View Point: Semaphorin-3E: An Emerging Modulator of Natural Killer Cell Functions?

    PubMed Central

    Alamri, Abdulaziz; Soussi Gounni, Abdelilah; Kung, Sam K. P.

    2017-01-01

    Semaphorin-3E (Sema-3E) is a member of a large family of proteins originally identified as axon guidance cues in neural development. It is expressed in different cell types, such as immune cells, cancer cells, neural cells, and epithelial cells. Subsequently, dys-regulation of Sema-3E expression has been reported in various biological processes that range from cancers to autoimmune and allergic diseases. Recent work in our laboratories revealed a critical immunoregulatory role of Sema-3E in experimental allergic asthma. We further speculate possible immune modulatory function(s) of Sema-3E on natural killer (NK) cells. PMID:29113093

  1. Particle Cooler/Generator Module in the MRM1

    NASA Image and Video Library

    2014-01-13

    ISS038-E-029764 (13 Jan. 2014) --- Russian cosmonaut Oleg Kotov, Expedition 38 commander, sets up the Particle Cooler/Generator Module for the Kaplya-2 experiment in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

  2. Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

    NASA Astrophysics Data System (ADS)

    Bernal-Martínez, Juan; Ortega Soto, Arturo

    2004-09-01

    Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

  3. Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by in-silico screening

    PubMed Central

    2013-01-01

    Background Ionotropic glutamate receptors (iGluAs, IUPHAR nomenclature) are the major excitatory amino acid neurotransmitter receptors in the mammalian central nervous system (CNS). iGluAs are potential therapeutic drug targets for various neurological disorders including ischemia, epilepsy, Parkinson’s and Alzheimer’s diseases. The known iGluA modulators, cyclothiazide (CTZ), IDRA-21, and other benzothiadiazide derivatives (ALTZ, HCTZ, and CLTZ) bind to the ligand-binding domain of flip-form of iGluA2 at the dimer interface, thereby increasing steady-state activation by reducing desensitization. Methods To discover new modulator compounds, we performed virtual screening for the ligand binding domain (LBD) of iGluA2 against NCI Diversity Set III library containing 1597 compounds, and subsequently performed binding-energy analysis for selected compounds. The crystal structure of rat iGluA2 S1S2J (PDB ID: 3IJO) was used for docking studies. Results and conclusion From this study, we obtained four compounds: (1) 10-2(methoxyethyl)-3-phenylbenzo[g]pteridine-2,4-dione, (2) 2-benzo[e]benzotriazol-2-yl-aniline, (3) 9-nitro-6H-indolo-(2,3,-b)quinoxaline, and (4) 1-hydroxy-n-(3-nitrophenyl)-2-napthamide. The binding mode of these four compounds is very similar to that of abovementioned established modulators: two molecules of each compound independently bind to the protein symmetrically at the dimer interface; occupy the subsites B, C, B’ and C’; potentially interact with Ser518 and Ser775. Binding energy analysis shows that all the four hits are comparable to the drug molecule, CTZ, and hence, we propose that the discovered hits may be potential molecules to develop new chemical libraries for modulating the flip form of iGluA2 function. PMID:23855825

  4. Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by in-silico screening.

    PubMed

    Padmanabhan, Balasundaram

    2013-07-15

    Ionotropic glutamate receptors (iGluAs, IUPHAR nomenclature) are the major excitatory amino acid neurotransmitter receptors in the mammalian central nervous system (CNS). iGluAs are potential therapeutic drug targets for various neurological disorders including ischemia, epilepsy, Parkinson's and Alzheimer's diseases. The known iGluA modulators, cyclothiazide (CTZ), IDRA-21, and other benzothiadiazide derivatives (ALTZ, HCTZ, and CLTZ) bind to the ligand-binding domain of flip-form of iGluA2 at the dimer interface, thereby increasing steady-state activation by reducing desensitization. To discover new modulator compounds, we performed virtual screening for the ligand binding domain (LBD) of iGluA2 against NCI Diversity Set III library containing 1597 compounds, and subsequently performed binding-energy analysis for selected compounds. The crystal structure of rat iGluA2 S1S2J (PDB ID: 3IJO) was used for docking studies. From this study, we obtained four compounds: (1) 10-2(methoxyethyl)-3-phenylbenzo[g]pteridine-2,4-dione, (2) 2-benzo[e]benzotriazol-2-yl-aniline, (3) 9-nitro-6H-indolo-(2,3,-b)quinoxaline, and (4) 1-hydroxy-n-(3-nitrophenyl)-2-napthamide. The binding mode of these four compounds is very similar to that of abovementioned established modulators: two molecules of each compound independently bind to the protein symmetrically at the dimer interface; occupy the subsites B, C, B' and C'; potentially interact with Ser518 and Ser775. Binding energy analysis shows that all the four hits are comparable to the drug molecule, CTZ, and hence, we propose that the discovered hits may be potential molecules to develop new chemical libraries for modulating the flip form of iGluA2 function.

  5. Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

    PubMed

    Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

    2017-03-01

    The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch

  6. Using Instructional Design, Analyze, Design, Develop, Implement, and Evaluate, to Develop e-Learning Modules to Disseminate Supported Employment for Community Behavioral Health Treatment Programs in New York State.

    PubMed

    Patel, Sapana R; Margolies, Paul J; Covell, Nancy H; Lipscomb, Cristine; Dixon, Lisa B

    2018-01-01

    Implementation science lacks a systematic approach to the development of learning strategies for online training in evidence-based practices (EBPs) that takes the context of real-world practice into account. The field of instructional design offers ecologically valid and systematic processes to develop learning strategies for workforce development and performance support. This report describes the application of an instructional design framework-Analyze, Design, Develop, Implement, and Evaluate (ADDIE) model-in the development and evaluation of e-learning modules as one strategy among a multifaceted approach to the implementation of individual placement and support (IPS), a model of supported employment for community behavioral health treatment programs, in New York State. We applied quantitative and qualitative methods to develop and evaluate three IPS e-learning modules. Throughout the ADDIE process, we conducted formative and summative evaluations and identified determinants of implementation using the Consolidated Framework for Implementation Research (CFIR). Formative evaluations consisted of qualitative feedback received from recipients and providers during early pilot work. The summative evaluation consisted of levels 1 and 2 (reaction to the training, self-reported knowledge, and practice change) quantitative and qualitative data and was guided by the Kirkpatrick model for training evaluation. Formative evaluation with key stakeholders identified a range of learning needs that informed the development of a pilot training program in IPS. Feedback on this pilot training program informed the design document of three e-learning modules on IPS: Introduction to IPS, IPS Job development, and Using the IPS Employment Resource Book . Each module was developed iteratively and provided an assessment of learning needs that informed successive modules. All modules were disseminated and evaluated through a learning management system. Summative evaluation revealed that

  7. H2O2 production rate in Lactobacillus johnsonii is modulated via the interplay of a heterodimeric flavin oxidoreductase with a soluble 28 Kd PAS domain containing protein

    PubMed Central

    Valladares, Ricardo B.; Graves, Christina; Wright, Kaitlyn; Gardner, Christopher L.; Lorca, Graciela L.; Gonzalez, Claudio F.

    2015-01-01

    Host and commensals crosstalk, mediated by reactive oxygen species (ROS), has triggered a growing scientific interest to understand the mechanisms governing such interaction. However, the majority of the scientific studies published do not evaluate the ROS production by commensals bacteria. In this context we recently showed that Lactobacillus johnsonii N6.2, a strain of probiotic value, modulates the activity of the critical enzymes 2,3-indoleamine dioxygenase via H2O2 production. L. johnsonii N6.2 by decreasing IDO activity, is able to modify the tryptophan/kynurenine ratio in the host blood with further systemic consequences. Understanding the mechanisms of H2O2 production is critical to predict the probiotic value of these strains and to optimize bacterial biomass production in industrial processes. We performed a transcriptome analysis to identify genes differentially expressed in L. johnsonii N6.2 cells collected from cultures grown under different aeration conditions. Herein we described the biochemical characteristics of a heterodimeric FMN reductase (FRedA/B) whose in vitro activity is controlled by LjPAS protein with a typical Per-Arnst-Sim (PAS) sensor domain. Interestingly, LjPAS is fused to the FMN reductase domains in other lactobacillaceae. In L. johnsonii, LjPAS is encoded by an independent gene which expression is repressed under anaerobic conditions (>3 fold). Purified LjPAS was able to slow down the FRedA/B initial activity rate when the holoenzyme precursors (FredA, FredB, and FMN) were mixed in vitro. Altogether the results obtained suggest that LjPAS module regulates the H2O2 production helping the cells to minimize oxidative stress in response to environmental conditions. PMID:26236298

  8. H2O2 production rate in Lactobacillus johnsonii is modulated via the interplay of a heterodimeric flavin oxidoreductase with a soluble 28 Kd PAS domain containing protein.

    PubMed

    Valladares, Ricardo B; Graves, Christina; Wright, Kaitlyn; Gardner, Christopher L; Lorca, Graciela L; Gonzalez, Claudio F

    2015-01-01

    Host and commensals crosstalk, mediated by reactive oxygen species (ROS), has triggered a growing scientific interest to understand the mechanisms governing such interaction. However, the majority of the scientific studies published do not evaluate the ROS production by commensals bacteria. In this context we recently showed that Lactobacillus johnsonii N6.2, a strain of probiotic value, modulates the activity of the critical enzymes 2,3-indoleamine dioxygenase via H2O2 production. L. johnsonii N6.2 by decreasing IDO activity, is able to modify the tryptophan/kynurenine ratio in the host blood with further systemic consequences. Understanding the mechanisms of H2O2 production is critical to predict the probiotic value of these strains and to optimize bacterial biomass production in industrial processes. We performed a transcriptome analysis to identify genes differentially expressed in L. johnsonii N6.2 cells collected from cultures grown under different aeration conditions. Herein we described the biochemical characteristics of a heterodimeric FMN reductase (FRedA/B) whose in vitro activity is controlled by LjPAS protein with a typical Per-Arnst-Sim (PAS) sensor domain. Interestingly, LjPAS is fused to the FMN reductase domains in other lactobacillaceae. In L. johnsonii, LjPAS is encoded by an independent gene which expression is repressed under anaerobic conditions (>3 fold). Purified LjPAS was able to slow down the FRedA/B initial activity rate when the holoenzyme precursors (FredA, FredB, and FMN) were mixed in vitro. Altogether the results obtained suggest that LjPAS module regulates the H2O2 production helping the cells to minimize oxidative stress in response to environmental conditions.

  9. Large-area and highly crystalline MoSe2 for optical modulator

    NASA Astrophysics Data System (ADS)

    Yin, Jinde; Chen, Hao; Lu, Wei; Liu, Mengli; Li, Irene Ling; Zhang, Min; Zhang, Wenfei; Wang, Jinzhang; Xu, Zihan; Yan, Peiguang; Liu, Wenjun; Ruan, Shuangchen

    2017-12-01

    Transition metal dichalcogenides (TMDs) have been successfully used as broadband optical modulator materials for pulsed fiber laser systems. However, the nonlinear optical absorptions of exfoliated TMDs are strongly limited by their nanoflakes morphology with uncontrollable lateral size and thickness. In this work, we provide an effective method to fully explore the nonlinear optical properties of MoSe2. Large-area and high quality lattice MoSe2 grown by chemical vapor deposition method was adopted as an optical modulator for the first time. The large-area MoSe2 shows excellent nonlinear optical absorption with a large modulation depth of 21.7% and small saturable intensity of 9.4 MW cm-2. After incorporating the MoSe2 optical modulator into fiber laser cavity as a saturable absorber, a highly stable Q-switching operation with single pulse energy of 224 nJ is achieved. The large-area MoSe2 possessing superior nonlinear optical properties compared to exfoliated nanoflakes affords possibility for the larger-area two-dimensional materials family as high performance optical devices.

  10. Differential modulation of microglia superoxide anion and thromboxane B2 generation by the marine manzamines

    PubMed Central

    Mayer, Alejandro MS; Hall, Mary L; Lynch, Sean M; Gunasekera, Sarath P; Sennett, Susan H; Pomponi, Shirley A

    2005-01-01

    Background Thromboxane B2 (TXB2) and superoxide anion (O2-) are neuroinflammatory mediators that appear to be involved in the pathogenesis of several neurodegenerative diseases. Because activated-microglia are the main source of TXB2 and O2- in these disorders, modulation of their synthesis has been hypothesized as a potential therapeutic approach for neuroinflammatory disorders. Marine natural products have become a source of novel agents that modulate eicosanoids and O2- generation from activated murine and human leukocytes. With the exception of manzamine C, all other manzamines tested are characterized by a complex pentacyclic diamine linked to C-1 of the β-carboline moiety. These marine-derived alkaloids have been reported to possess a diverse range of bioactivities including anticancer, immunostimulatory, insecticidal, antibacterial, antimalarial and antituberculosis activities. The purpose of this investigation was to conduct a structure-activity relationship study with manzamines (MZ) A, B, C, D, E and F on agonist-stimulated release of TXB2 and O2- from E. coli LPS-activated rat neonatal microglia in vitro. Results The manzamines differentially attenuated PMA (phorbol 12-myristate 13-acetate)-stimulated TXB2 generation in the following order of decreasing potency: MZA (IC50 <0.016 μM) >MZD (IC50 = 0.23 μM) >MZB (IC50 = 1.6 μM) >MZC (IC50 = 2.98 μM) >MZE and F (IC50 >10 μM). In contrast, there was less effect on OPZ (opsonized zymosan)-stimulated TXB2 generation: MZB (IC50 = 1.44 μM) >MZA (IC50 = 3.16 μM) >MZC (IC50 = 3.34 μM) >MZD, MZE and MZF (IC50 >10 μM). Similarly, PMA-stimulated O2- generation was affected differentially as follows: MZD (apparent IC50<0.1 μM) >MZA (IC50 = 0.1 μM) >MZB (IC50 = 3.16 μM) >MZC (IC50 = 3.43 μM) >MZE and MZF (IC50 >10 μM). In contrast, OPZ-stimulated O2- generation was minimally affected: MZB (IC50 = 4.17 μM) >MZC (IC50 = 9.3 μM) >MZA, MZD, MZE and MZF (IC50 > 10 μM). From the structure

  11. An assessment of the feasibility and effectiveness of an e-learning module in delivering a curriculum in radiation protection to undergraduate medical students.

    PubMed

    Leong, Sum; Mc Laughlin, Patrick; O'Connor, Owen J; O'Flynn, Siun; Maher, Michael M

    2012-03-01

    Integrating radiation protection (RP) education in the undergraduate medical curriculum is gaining importance and is mandatory in certain jurisdictions. An e-learning module for RP was developed at the authors' medical school and was integrated into year 4 of the 5-year undergraduate medical program. The aim of this study was to investigate its impact on RP knowledge, student preferences for various teaching methods, self-assessment of RP knowledge, and perceptions of career prospects in radiology. Likert-type 5-point scale evaluations and general comments about the RP module and various methods of teaching were also obtained. An e-learning module in RP was designed and presented to year 4 medical undergraduates. All students were required to complete premodule and postmodule questionnaires. Eighty-nine percent (n = 113) and 99% (n = 126) of the 127 medical students successfully completed and returned the premodule and postmodule questionnaires, respectively. After the e-learning module, students' postmodule RP knowledge had improved significantly. Analysis of postmodule RP knowledge suggested that a favorable self-assessment of knowledge of RP, perception of career prospects in radiology, and completion of the e-learning module with an increased number of sessions were factors predictive of improved RP knowledge. Students expressed a preference for didactic lectures and clinical attachment for instruction in RP over e-learning. The development of an e-learning module in RP is feasible and results in improved knowledge of RP among medical undergraduates. Combining e-learning and more traditional educational programs such as a clinical radiology rotation is likely to improve student experience. Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  12. E-Learning for 4-H Volunteers: Who Uses It, and What Can We Learn from Them?

    ERIC Educational Resources Information Center

    Ouellette, Kristy L.; Lesmeister, Marilyn K.; Lobley, Jennifer; Gross, Kerry M.

    2014-01-01

    Orienting and training 4-H volunteers are critical to individuals and the organization. The two-part study reported here re-establishes the profile of the 4-H volunteer and evaluates both the format and content of e-Learning for 4-H Volunteers modules launched in 2006. Volunteers from seven states perceived that online modules made learning more…

  13. Pigment composition and concentrations within the plant (Ceratophyllum demersum L.) component of the STS-89 C.E.B.A.S. Mini-Module spaceflight experiment

    NASA Technical Reports Server (NTRS)

    Voeste, D.; Levine, L. H.; Levine, H. G.; Blum, V.; Wheeler, R. M. (Principal Investigator)

    2003-01-01

    The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) Mini-Module, a Space Shuttle middeck locker payload which supports a variety of aquatic inhabitants (fish, snails, plants and bacteria) in an enclosed 8.6 L chamber, was tested for its biological stability in microgravity. The aquatic plant, Ceratophyllum demersum L., was critical for the vitality and functioning of this artificial mini-ecosystem. Its photosynthetic pigment concentrations were of interest due to their light harvesting and protective functions. "Post-flight" chlorophyll and carotenoid concentrations within Ceratophyllum apical segments were directly related to the quantities of light received in the experiments, with microgravity exposure (STS-89) failing to account for any significant deviation from ground control studies. Published by Elsevier Science Ltd on behalf of COSPAR.

  14. XUV pulse effect on signal modulations of harmonic spectra from H2+ and T2+

    NASA Astrophysics Data System (ADS)

    Feng, Liqiang; Liu, Hang; Kapteyn, Henry J.; Feng, April Y.

    2018-05-01

    The effects of signal modulations on the molecular high-order harmonic generations in H2^{+ } and T2+ have been theoretically investigated. It is found that with the introduction of the XUV pulse, due to the absorption of the extra XUV photons in the recombination process, multiplateaus on the harmonic spectra, separated by the XUV photon energy can be found. Moreover, this multiplateau structure is insensitive to the wavelength of the XUV pulse. In shorter pulse duration, the intensities of the multiplateaus from H2+ are higher than those from T2+; while in longer pulse duration, the opposite results can be found. Finally, by changing the delay time of the XUV pulse, the signal modulations (including the amplitude and the frequency modulations) of the multiplateaus can be controlled.

  15. Broadband and high modulation-depth THz modulator using low bias controlled VO2-integrated metasurface.

    PubMed

    Zhou, Gaochao; Dai, Penghui; Wu, Jingbo; Jin, Biaobing; Wen, Qiye; Zhu, Guanghao; Shen, Ze; Zhang, Caihong; Kang, Lin; Xu, Weiwei; Chen, Jian; Wu, Peiheng

    2017-07-24

    An active vanadium dioxide integrated metasurface offering broadband transmitted terahertz wave modulation with large modulation-depth under electrical control is demonstrated. The device consists of metal bias-lines arranged with grid-structure patterned vanadium dioxide (VO 2 ) film on sapphire substrate. Amplitude transmission is continuously tuned from more than 78% to 28% or lower in the frequency range from 0.3 THz to 1.0 THz, by means of electrical bias at temperature of 68 °C. The physical mechanism underlying the device's electrical tunability is investigated and found to be attributed to the ohmic heating. The developed device possessing over 87% modulation depth with 0.7 THz frequency band is expected to have many potential applications in THz regime such as tunable THz attenuator.

  16. Validation of an e-Learning 3.0 Critical Success Factors Framework: A Qualitative Research

    ERIC Educational Resources Information Center

    Miranda, Paula; Isaias, Pedro; Costa, Carlos J.; Pifano, Sara

    2017-01-01

    Aim/Purpose: As e-Learning 3.0 evolves from a theoretical construct into an actual solution for online learning, it becomes crucial to accompany this progress by scrutinising the elements that are at the origin of its success. Background: This paper outlines a framework of e-Learning 3.0's critical success factors and its empirical validation.…

  17. FOXP2, APOE, and PRNP: new modulators in primary progressive aphasia.

    PubMed

    Premi, Enrico; Pilotto, Andrea; Alberici, Antonella; Papetti, Alice; Archetti, Silvana; Seripa, Davide; Daniele, Antonio; Masullo, Carlo; Garibotto, Valentina; Paghera, Barbara; Caobelli, Federico; Padovani, Alessandro; Borroni, Barbara

    2012-01-01

    Primary progressive aphasia (PPA) is a heterogeneous disorder characterized by progressive language impairment. Polymorphisms within forkhead box P2 gene (FOXP2) gene have been associated with speech and language impairment. Apolipoprotein E (APOE) genotype and PRNP 129 codon status have been demonstrated to increase the risk of PPA, but with contrasting results. In the present study, we have evaluated the impact of FOXP2, APOE and PRNP genetic variations as risk factors and/or disease-modulators in PPA. 94 PPA patients and 200 age-matched healthy controls were considered and FOXP2 polymorphisms (rs1456031, rs17137124), APOE genotype, and PRNP codon 129 polymorphism analyzed. In 34 PPA patients, SPECT imaging data were analyzed by Statistical Parametric Mapping (SPM8). Genetic distributions and allele frequencies of FOXP2 and PRNP polymorphisms did not differ between groups while APOE ε4 was more represented in PPA as compared to controls. PPA patients carrying at-risk FOXP2 polymorphisms (rs1456031 and/or rs17137124) showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus and the right cingulated gyrus compared to non-carriers (p < 0.005). PPA patients carrying at least one ε4 allele had greater hypoperfusion in orbitofrontal regions (superior frontal gyrus and orbital gyrus) as compared to non-carriers ε4 (p < 0.005). PRNP codon 129 homozigosity correlated with left frontotemporal hypoperfusion (p < 0.005). Genetic variations within FOXP2, APOE, and PRNP modulate PPA disease, leading to a specific regional hypoperfusion according to different molecular pathways. APOE ε4 is overrepresented in PPA, thus likely acting as genetic risk factor on disease development.

  18. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    The Orion crew module for Exploration Mission-1 was moved into the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  19. Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

    PubMed Central

    Awara, W; Hillier, K; Jones, D

    1986-01-01

    The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect. PMID:3468061

  20. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F1--F8 -- Volume 2, Part 1, Revision 4

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

    Greene, N.M.; Petrie, L.M.; Westfall, R.M.

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system hasmore » been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation; Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries.« less

  1. Modulation of N-glycosylation by mesalamine facilitates membranous E-cadherin expression in colon epithelial cells☆

    PubMed Central

    Khare, Vineeta; Lang, Michaela; Dammann, Kyle; Campregher, Christoph; Lyakhovich, Alex; Gasche, Christoph

    2014-01-01

    Genome wide association studies have implicated intestinal barrier function genes in the pathogenesis of ulcerative colitis. One of such loci CDH1, encoding E-cadherin, a transmembrane glycoprotein with known tumor suppressor functions, is also linked to the susceptibility to colorectal cancer. Loss of membranous E-cadherin expression is common in both colitis and cancer. We have recently demonstrated that mesalamine (5-ASA); the anti-inflammatory drug used to treat ulcerative colitis, induces membranous expression of E-cadherin and increases intercellular adhesion. Using colorectal cancer epithelial cells with aberrant E-cadherin expression, we investigated the mechanism underlying such an effect of 5-ASA. Post-translational modification of E-cadherin glycosylation was analyzed by biotin/streptavidin detection of sialylated glycoproteins. GnT-III (N-acetylglucosaminyltransferase III) expression was assessed by qRT-PCR, Western blot and immunofluorescence. GnT-III activity was analyzed by reactivity with E-4/L-4-PHA. Expression, localization and interaction of E-cadherin and β-catenin were analyzed by Western blot, immunocytochemistry and RNA interference. 5-ASA activity modulated E-cadherin glycosylation and increased both mRNA and protein levels of GnT-III and its activity as detected by increased E4-lectin reactivity. Intestinal APCMin polyps in mice showed low expression of GnT-III and 5-ASA was effective in increasing its expression. The data demonstrated that remodeling of glycans by GnT-III mediated bisect glycosylation, contributes to the membranous retention of E-cadherin by 5-ASA; facilitating intercellular adhesion. Induction of membranous expression of E-cadherin by 5-ASA is a novel mechanism for mucosal healing in colitis that might impede tumor progression by modulation of GnT-III expression. PMID:24184502

  2. Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.

    PubMed

    Hojo, Yasushi; Munetomo, Arisa; Mukai, Hideo; Ikeda, Muneki; Sato, Rei; Hatanaka, Yusuke; Murakami, Gen; Komatsuzaki, Yoshimasa; Kimoto, Tetsuya; Kawato, Suguru

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Dynamic e-Learning Modules for Student Lecture Preparation

    ERIC Educational Resources Information Center

    McIntyre, Timothy; Wegener, Margaret; McGrath, Dominic

    2018-01-01

    We have developed and demonstrated the effectiveness of a set of online interactive learning modules to accompany physics courses at first- and second-year university levels. Students access the modules prior to attending lectures to familiarize themselves with content which is then discussed and reaffirmed in class. Student surveys and access…

  4. Critical success factors in implementing an e-rostering system in a healthcare organisation.

    PubMed

    Soomro, Zahoor A; Ahmed, Javed; Muhammad, Raza; Hayes, Dawn; Shah, Mahmood H

    2017-01-01

    Effective and efficient staff scheduling has always been a challenging issue, especially in health service organisations. Both the extremes of staff shortage and overage have an adverse impact on the performance of healthcare organisations. In this case, an electronic and systematic staff scheduling (e-rostering) system is the often seen as the best solution. Unless an organisation has an effective implementation of such a system, possible cost savings, efficiency, and benefits could be minimal. This study is aimed to research key success factors for the successful effective implementation of an electronic rostering system, especially at healthcare organisations. A case study research method was used to evaluate critical success factors for effectively implementing an e-rostering system. The data were collected through interviews and observations. The findings indicate that technical support, an effective policy, leadership, clear goals and objectives, gradual change, evidence of the advantages of the new system, senior management support, and effective communication are the critical success factors in implementing an e-rostering system in healthcare organisations. Prior to this study, no such factors were grounded in the current context, so this research would help in bridging the gap towards effective implementation of an e-rostering system in the healthcare sector. This research also suggests future studies in different cultures and contexts.

  5. ERBB2 Deficiency Alters an E2F-1-Dependent Adaptive Stress Response and Leads to Cardiac Dysfunction

    PubMed Central

    Perry, Marie-Claude; Dufour, Catherine R.; Eichner, Lillian J.; Tsang, David W. K.; Deblois, Geneviève; Muller, William J.

    2014-01-01

    The tyrosine kinase receptor ERBB2 is required for normal development of the heart and is a potent oncogene in breast epithelium. Trastuzumab, a monoclonal antibody targeting ERBB2, improves the survival of breast cancer patients, but cardiac dysfunction is a major side effect of the drug. The molecular mechanisms underlying how ERBB2 regulates cardiac function and why trastuzumab is cardiotoxic remain poorly understood. We show here that ERBB2 hypomorphic mice develop cardiac dysfunction that mimics the side effects observed in patients treated with trastuzumab. We demonstrate that this phenotype is related to the critical role played by ERBB2 in cardiac homeostasis and physiological hypertrophy. Importantly, genetic and therapeutic reduction of ERBB2 activity in mice, as well as ablation of ERBB2 signaling by trastuzumab or siRNAs in human cardiomyocytes, led to the identification of an impaired E2F-1-dependent genetic program critical for the cardiac adaptive stress response. These findings demonstrate the existence of a previously unknown mechanistic link between ERBB2 and E2F-1 transcriptional activity in heart physiology and trastuzumab-induced cardiac dysfunction. PMID:25246633

  6. MCT IR detection modules with 15 µm pitch for high-reliability applications

    NASA Astrophysics Data System (ADS)

    Breiter, R.; Ihle, T.; Wendler, J.; Lutz, H.; Rutzinger, S.; Schallenberg, T.; Hofmann, K.; Ziegler, J.

    2010-04-01

    Additional to the development of 3rd Gen IR modules like dual-band and dual-color devices AIM is focused on IR FPAs with reduced pitch. These FPAs allow manufacturing of compact low cost IR modules with minimum power consumption for state-of-the-art high performance IR systems. AIM has realized full TV format MCT 640x512 mid-wave and long-wave IR detection modules with a 15 μm pitch to meet the requirements of critical military applications like thermal weapon sights or thermal imagers in UAV applications. In typical configurations like a F/4.6 cold shield for the 640x512 MWIR module an NETD < 25 mK @ 5 ms integration time is achieved, while the LWIR modules achieve an NETD < 38 mK @ F/2 and 180 μs integration time. For the LWIR modules FPAs with a cut-off of 9 and 10 μm have been realized. The modules are available either with different integral rotary cooler configurations for portable applications which require minimum cooling power or a new split linear cooler providing long lifetime with a MTTF > 20,000 h as required e.g. for warning sensors in 24/7 operation. The modules are available with an optional image processing electronics providing non-uniformity correction and further image processing for a complete IR imaging solution. A double field of view FLIR for an upgrade of the German Army UAV LUNA has been developed by AIM using the MCT 640x512 MWIR 15μm pitch engine. The latest results and performance of those modules and their applications are presented.

  7. Unified Technical Concepts. Module 2: Work.

    ERIC Educational Resources Information Center

    Technical Education Research Center, Waco, TX.

    This concept module on work is one of thirteen modules that provide a flexible, laboratory-based physics instructional package designed to meet the specialized needs of students in two-year, postsecondary technical schools. Each of the thirteen concept modules discusses a single physics concept and how it is applied to each energy system. In this…

  8. Evaluation of an active learning module to teach hazard and risk in Hazard Analysis and Critical Control Points (HACCP) classes.

    PubMed

    Oyarzabal, Omar A; Rowe, Ellen

    2017-04-01

    The terms hazard and risk are significant building blocks for the organization of risk-based food safety plans. Unfortunately, these terms are not clear for some personnel working in food manufacturing facilities. In addition, there are few examples of active learning modules for teaching adult participants the principles of hazard analysis and critical control points (HACCP). In this study, we evaluated the effectiveness of an active learning module to teach hazard and risk to participants of HACCP classes provided by the University of Vermont Extension in 2015 and 2016. This interactive module is comprised of a questionnaire; group playing of a dice game that we have previously introduced in the teaching of HACCP; the discussion of the terms hazard and risk; and a self-assessment questionnaire to evaluate the teaching of hazard and risk. From 71 adult participants that completed this module, 40 participants (56%) provided the most appropriate definition of hazard, 19 participants (27%) provided the most appropriate definition of risk, 14 participants (20%) provided the most appropriate definitions of both hazard and risk, and 23 participants (32%) did not provide an appropriate definition for hazard or risk. Self-assessment data showed an improvement in the understanding of these terms (P < 0.05). Thirty participants (42%) stated that the most valuable thing they learned with this interactive module was the difference between hazard and risk, and 40 participants (65%) responded that they did not attend similar presentations in the past. The fact that less than one third of the participants answered properly to the definitions of hazard and risk at baseline is not surprising. However, these results highlight the need for the incorporation of modules to discuss these important food safety terms and include more active learning modules to teach food safety classes. This study suggests that active learning helps food personnel better understand important food safety

  9. LUNAR MODULE TEST ARTICLE [LTA] [2R] IS MOVED FOR MATING TO LUNAR MODULE ADAPTER

    NASA Technical Reports Server (NTRS)

    1967-01-01

    The Lunar Module Test Article [LTA] 2R, for the second Saturn V mission, is being moved from the low bay of the Manned Spacecraft Operations Building for mating with the spacecraft Lunar Module Adapter. The second Saturn V [502], except for a different lunar return trajectory, will be a repeat of the Apollo 4 unmanned Earth orbital flight of a high apogee for systems testing using several propulsion system burns and a heat shield test at lunar re-entry speed.

  10. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.

    PubMed

    Lee, Miyoung; Oprea-Ilies, Gabriela; Saavedra, Harold I

    2015-11-10

    The E2F transcriptional activators E2F1, E2F2 and E2F3a regulate many important cellular processes, including DNA replication, apoptosis and centrosome duplication. Previously, we demonstrated that silencing E2F1 or E2F3 suppresses centrosome amplification (CA) and chromosome instability (CIN) in Her2+ breast cancer cells without markedly altering proliferation. However, it is unknown whether and how silencing a single E2F activator, E2F3, affects malignancy of human breast cancer cells. Thus, we injected HCC1954 Her2+ breast cancer cells silenced for E2F3 into mammary fat pads of immunodeficient mice and demonstrated that loss of E2F3 retards tumor growth. Surprisingly, silencing of E2F3 led to significant reductions in mitotic indices relative to vector controls, while the percentage of cells undergoing S phase were not affected. Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA. In this report, we found that Nek2 overexpression rescued back the CA caused by silencing of shE2F3. However, the effects of Nek2 overexpression in affecting tumor growth rates of shE2F3 and shE2F3; GFP cells were inconclusive. Taken together, our results indicate that E2F3 silencing decreases mammary tumor growth by reducing percentage of cells undergoing mitosis.

  11. Design and Status of the Mu2e Crystal Calorimeter

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

    Atanov, N.; et al.

    2018-01-08

    The Mu2e experiment at Fermilab searches for the charged-lepton flavour violating (CLFV) conversion of a negative muon into an electron in the field of an aluminum nucleus, with a distinctive signature of a mono-energetic electron of energy slightly below the muon rest mass (104.967 MeV). The Mu2e goal is to improve by four orders of magnitude the search sensitivity with respect to the previous experiments. Any observation of a CLFV signal will be a clear indication of new physics. The Mu2e detector is composed of a tracker, an electro- magnetic calorimeter and an external veto for cosmic rays surrounding themore » solenoid. The calorimeter plays an important role in providing particle identification capabilities, a fast online trigger filter, a seed for track reconstruction while working in vacuum, in the presence of 1 T axial magnetic field and in an harsh radiation environment. The calorimeter requirements are to provide a large acceptance for 100 MeV electrons and reach at these energies: (a) a time resolution better than 0.5 ns; (b) an energy resolution < 10% and (c) a position resolution of 1 cm. The calorimeter design consists of two disks, each one made of 674 undoped CsI crystals read by two large area arrays of UV-extended SiPMs. We report here the construction and test of the Module-0 prototype. The Module-0 has been exposed to an electron beam in the energy range around 100 MeV at the Beam Test Facility in Frascati. Preliminary results of timing and energy resolution at normal incidence are shown. A discussion of the technical aspects of the calorimeter engineering is also reported in this paper.« less

  12. Parafoveal Load of Word N+1 Modulates Preprocessing Effectiveness of Word N+2 in Chinese Reading

    ERIC Educational Resources Information Center

    Yan, Ming; Kliegl, Reinhold; Shu, Hua; Pan, Jinger; Zhou, Xiaolin

    2010-01-01

    Preview benefits (PBs) from two words to the right of the fixated one (i.e., word N + 2) and associated parafoveal-on-foveal effects are critical for proposals of distributed lexical processing during reading. This experiment examined parafoveal processing during reading of Chinese sentences, using a boundary manipulation of N + 2-word preview…

  13. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells

    PubMed Central

    2013-01-01

    and breast cancer and suggest that progression, and metastasis, of advanced stages of breast cancer can be modulated by induction of CYP2E1 activity. PMID:24207099

  14. The impact of e-marketing orientation on performance in Asian SMEs: a B2B perspective

    NASA Astrophysics Data System (ADS)

    Chong, Woon Kian; Man, Ka Lok; Kim, Mucheol

    2018-01-01

    Business-to-business (B2B) organisations are increasingly utilising electronic devices in their business operations in order to succeed in increasingly competitive markets. This trend is prevalent in the growing Asian markets, especially in the small and medium-sized enterprises (SMEs) sector. While prior research has focused on this issue in the context of large business-to-customer (B2C) organisations in Asia, there have hardly been any studies that have shed light on the B2B sector in the SME setting. This study aims to critically explore B2B e-marketing critical success factors (B2B-eM-CSFs) for SMEs operating in the Asian B2B marketplace. A key finding is the development of a theoretical framework for SMEs, emerging from the analysis of 406 companies from various industrial sectors. The study shows that interaction with the B2B-eM-CSFs is an important dimension and has a positive and significant impact on e-business efficiency and marketing improvements for Asian SMEs.

  15. The eROSITA X-ray mirrors: technology and qualification aspects of the production of mandrels, shells and mirror modules

    NASA Astrophysics Data System (ADS)

    Arcangeli, L.; Borghi, G.; Bräuninger, H.; Citterio, O.; Ferrario, I.; Friedrich, P.; Grisoni, G.; Marioni, F.; Predehl, P.; Rossi, M.; Ritucci, A.; Valsecchi, G.; Vernani, D.

    2017-11-01

    The name "eROSITA" stands for extended Roentgen Survey with an Imaging Telescope Array. The general design of the eROSITA X-ray telescope is derived from that of ABRIXAS. A bundle of 7 mirror modules with short focal lengths make up a compact telescope which is ideal for survey observations. Similar designs had been proposed for the missions DUO and ROSITA but were not realized due to programmatic shortfall. Compared to those, however, the effective area in the soft X-ray band has now much increased by adding 27 additional outer mirror shells to the original 27 ones of each mirror module. The requirement on the on-axis resolution has also been confined, namely to 15 arc seconds HEW. For these reasons the prefix "extended" was added to the original name "ROSITA". The scientific motivation for this extension is founded in the ambitious goal to detect about 100,000 clusters of galaxies which trace the large scale structure of the Universe in space and time. The X-ray telescope of eROSITA will consist of 7 identical and co-aligned mirror modules, each with 54 nested Wolter-1 mirror shells. The mirror shells are glued onto a spider wheel which is screwed to the mirror interface structure making a rigid mechanical unit. The assembly of 7 modules forms a compact hexagonal configuration with 1300 mm diameter (see Fig. 1) and will be attached to the telescope structure which connects to the 7 separate CCD cameras in the focal planes. The co-alignment of the mirror module enables eROSITA to perform also pointed observations. The replication process described in chapter III allows the manufacturing in one single piece and at the same time of both the parabola and hyperbola parts of the Wolter 1 mirror.

  16. E = Mc(super 2) for the Chemist: When is Mass Conserved?

    ERIC Educational Resources Information Center

    Treptow. Richard S.

    2005-01-01

    An equation derived by Albert Einstein in 1905 that expresses a relationship between mass and energy, formulated as E = mc(super 2) is discussed with reference to the extent mass is conserved. This query can be used to challenge students and develop their language and critical thinking skills.

  17. Unusually high critical current of clean P-doped BaFe2As2 single crystalline thin film

    NASA Astrophysics Data System (ADS)

    Kurth, F.; Tarantini, C.; Grinenko, V.; Hänisch, J.; Jaroszynski, J.; Reich, E.; Mori, Y.; Sakagami, A.; Kawaguchi, T.; Engelmann, J.; Schultz, L.; Holzapfel, B.; Ikuta, H.; Hühne, R.; Iida, K.

    2015-02-01

    Microstructurally clean, isovalently P-doped BaFe2As2 (Ba-122) single crystalline thin films have been prepared on MgO (001) substrates by molecular beam epitaxy. These films show a superconducting transition temperature (Tc) of over 30 K although P content is around 0.22, which is lower than the optimal one for single crystals (i.e., 0.33). The enhanced Tc at this doping level is attributed to the in-plane tensile strain. The strained film shows high transport self-field critical current densities (Jc) of over 6 MA/cm2 at 4.2 K, which are among the highest for Fe based superconductors (FeSCs). In-field Jc exceeds 0.1 MA/cm2 at μ 0 H = 35 T for H ‖ a b and μ 0 H = 18 T for H ‖ c at 4.2 K, respectively, in spite of moderate upper critical fields compared to other FeSCs with similar Tc. Structural investigations reveal no defects or misoriented grains pointing to strong pinning centers. We relate this unexpected high Jc to a strong enhancement of the vortex core energy at optimal Tc, driven by in-plane strain and doping. These unusually high Jc make P-doped Ba-122 very favorable for high-field magnet applications.

  18. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    PubMed Central

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  19. Basic Stabilization. Training Module 2.225.2.77.

    ERIC Educational Resources Information Center

    Paulson, W. L.

    This document is an instructional module package prepared in objective form for use by an instructor familiar with water stabilization and deposition and corrosion control in a water supply system. Included are objectives, an instructor guide, student handouts and transparency masters. The module considers water stability, water chemistry,…

  20. Pre-Treatment. Training Module 2.102.2.77.

    ERIC Educational Resources Information Center

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document is an instructional module package designed in the objective format for use by an instructor familiar with pre-treatment unit operation. Included are objectives, instructor guide, student handouts and transparency masters. The module considers design, operation, maintenance, and safety of common methods of grit removal, screening,…

  1. Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

    PubMed

    Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

    2018-05-01

    Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. ON CRITICAL MASS ANALYSIS OF JRR-2

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

    None

    1961-01-01

    The critica mass of the JRR-2 was found to be 15 fuel elements, instead of 8 as expected, when the reactor reached criticaity. The critica mass was analyzed by AMF and JAERI a few years ago, but afterwards some modifications have been made of the stucture for the reinforcement, for example, during the construction. The critical mass is recalculated perfectly and the difference bctween 15 and S fuel elements is discussed. The deviation of the critical mass is mainly caused by the effects of control rods, fuel elcments, grid-plate, etc., in the reflector; only heavy water or light water wasmore » conaidered as the reflector in the previous calculation. A simple method is used to calculate the critical mass. The effective multiplication factor for the core with 15 fuel elements is obtained about 2% higher than the experimental value. This difference is also discussed in detail. (auth)« less

  3. Energy modulation of nonrelativistic electrons with a CO2 laser using a metal microslit

    NASA Astrophysics Data System (ADS)

    Bae, Jongsuck; Ishikawa, Ryo; Okuyama, Sumio; Miyajima, Takashi; Akizuki, Taiji; Okamoto, Tatsuya; Mizuno, Koji

    2000-04-01

    A metal microslit has been used as an interaction circuit between a CO2 laser beam and nonrelativistic free electrons. Evanescent waves which are induced on the slit by illumination of the laser light modulate the energy of electrons passing close to the surface of the slit. The electron-energy change of more than ±5 eV for the 80 keV electron beam has been observed using the 7 kW laser beam at the wavelength of 10.6 μm.

  4. Aquatic modules for bioregenerative life support systems based on the C.E.B.A.S. biotechnology [correction of biotechnilogy].

    PubMed

    Bluem, V; Paris, F

    2001-01-01

    Most concepts for bioregenerative life support systems are based on edible higher land plants which create some problems with growth and seed generation under space conditions. Animal protein production is mostly neglected because of the tremendous waste management problems with tetrapods under reduced weightlessness. Therefore, the "Closed Equilibrated Biological Aquatic System" (C.E.B.A.S.) was developed which represents an artificial aquatic ecosystem containing aquatic organisms which are adapted at all to "near weightlessness conditions" (fishes Xiphophorus helleri, water snails Biomphalaria glabrata, ammonia oxidizing bacteria and the rootless non-gravitropic edible water plant Ceratophyllum demersum). Basically the C.E.B.A.S. consists of 4 subsystems: a ZOOLOGICAL (correction of ZOOLOGICASL) COMPONENT (animal aquarium), a BOTANICAL COMPONENT (aquatic plant bioreactor), a MICROBIAL COMPONENT (bacteria filter) and an ELECTRONICAL COMPONENT (data acquisition and control unit). Superficially, the function principle appears simple: the plants convert light energy into chemical energy via photosynthesis thus producing biomass and oxygen. The animals and microorganisms use the oxygen for respiration and produce the carbon dioxide which is essential for plant photosynthesis. The ammonia ions excreted by the animals are converted by the bacteria to nitrite and then to nitrate ions which serve as a nitrogen source for the plants. Other essential ions derive from biological degradation of animal waste products and dead organic matter. The C.E.B.A.S. exists in 2 basic versions: the original C.E.B.A.S. with a volume of 150 liters and a self-sustaining standing time of more than 13 month and the so-called C.E.B.A.S. MINI MODULE with a volume of about 8.5 liters. In the latter there is no closed food loop by reasons of available space so that animal food has to be provided via an automated feeder. This device was flown already successfully on the STS-89 and STS-90

  5. Professional Teacher Education Module Series. Provide for the First Aid Needs of Students, Module E-6 of Category E--Instructional Management.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This sixth in a series of nine learning modules on instructional management is designed to assist secondary and postsecondary vocational teachers in establishing and maintaining a procedure for attending to the basic first aid needs of students. Introductory sections relate the competency dealt with in this module to others in the program and list…

  6. Mining a human transcriptome database for Nrf2 modulators

    EPA Science Inventory

    Nuclear factor erythroid-2 related factor 2 (Nrf2) is a key transcription factor important in the protection against oxidative stress. We developed computational procedures to enable the identification of chemical, genetic and environmental modulators of Nrf2 in a large database ...

  7. A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization

    PubMed Central

    Vilaboa, Nuria; Bermejo, Rodrigo; Martinez, Pilar; Bornstein, Rafael; Calés, Carmela

    2004-01-01

    Cdc6 is a key regulator of the strict alternation of S and M phases during the mitotic cell cycle. In mammalian and plant cells that physiologically become polyploid, cdc6 is transcriptionally and post-translationally regulated. We have recently reported that Cdc6 levels are maintained in megakaryoblastic HEL cells, but severely downregulated by ectopic expression of transcriptional repressor Drosophila melanogaster escargot. Here, we show that cdc6 promoter activity is upregulated during megakaryocytic differentiation of HEL endoreplicating cells, and that Escargot interferes with such activation. Transactivation experiments showed that a 1.7 kb region located at 2800 upstream cdc6 transcription initiation site behaved as a potent enhancer in endoreplicating cells only. This activity was mainly dependent on a novel cis-regulatory element composed by an E2 box overlapping a GATA motif. Ectopic Escargot could bind this regulatory element in vitro and endogenous GATA-1 and E2A formed specific complexes in megakaryoblastic cells as well as in primary megakaryocytes. Chromatin Immunoprecipitation analysis revealed that both transcription factors were occupying the E2 box/GATA site in vivo. Altogether, these data suggest that cdc6 expression could be actively maintained during megakaryocytic differentiation through transcriptional mechanisms involving specific cis- and trans-regulatory elements. PMID:15590906

  8. GOMA: functional enrichment analysis tool based on GO modules

    PubMed Central

    Huang, Qiang; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun

    2013-01-01

    Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results. PMID:23237213

  9. Modulation of Nrf2/Keap1 system by Wasabi 6-methylthiohexyl isothiocyanate in ARE-mediated NQO1 expression.

    PubMed

    Korenori, Yoshimi; Tanigawa, Shunsuke; Kumamoto, Takuma; Qin, Si; Daikoku, Yosuke; Miyamori, Koji; Nagai, Masashi; Hou, De-Xing

    2013-05-01

    6-Methylthiohexyl isothiocyanate (6-MTITC), one of the major bioactive ingredients in Japanese Wasabi, has revealed cytoprotective and cancer chemopreventive effects. This study aims to clarify the molecular mechanisms how 6-MTITC modulates nuclear factor E2-related factor 2 (Nrf2)/Kelchlike ECH-associating protein 1 (Keap1) system in antioxidant-responsive element (ARE)-mediated nicotinamide adenine dinucleotide phosphate (NADP): quinone oxidoreductase 1 (NQO1) expression. HepG2 cells were treated with 6-MTITC with varying time and dose. NQO1, Nrf2, and Keap1 proteins were detected by Western blotting. ARE transactivation was detected by electrophilic mobility shift assay and reporter gene assay. Nuclear localization of Nrf2 was determined by immunocytochemistry assay. Ubiquitination of Nrf2 and Keap1 was detected using immunoprecipitation after treatment with MG132. Small interfering RNA was used to knockdown Nrf2 or Keap1. The results revealed that 6-MTITC modulated Nrf2/ARE pathway by stimulating Keap1 modification, and inhibiting Nrf2 ubiquitination and protein turnover. These actions finally increased nuclear Nrf2 accumulation and ARE-binding activity. Moreover, silencing Nrf2 markedly reduced ARE-driven activity induced by 6-MTITC. 6-MTITC modulated ARE-driven NQO1 expression by stabilizing Nrf2 with enhanced Keap1 modification and decreased Nrf2 degradation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway

    PubMed Central

    Zhang, Rong; Lu, Huan; Lyu, Yuan-yuan; Yang, Xiao-mei; Zhu, Lin-yan; Yang, Guang-dong; Jiang, Peng-cheng; Re, Yuan; Song, Wei-wei; Wang, Jin-hao; Zhang, Can-can; Gu, Fei; Luo, Tian-jiao; Wu, Zhi-yong; Xu, Cong-jian

    2017-01-01

    Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis. PMID:28303973

  11. Carboxysomes: metabolic modules for CO 2 fixation

    DOE PAGES

    Turmo, Aiko; Gonzalez-Esquer, Cesar Raul; Kerfeld, Cheryl A.

    2017-08-14

    The carboxysome is a bacterial microcompartment encapsulating the enzymes carbonic anhydrase and ribulose-1,5-bisphosphate carboxylase/oxygenase. As the site of CO 2 fixation, it serves an essential role in the carbon dioxide concentrating mechanism of many chemoautotrophs and all cyanobacteria. Carboxysomes and other bacterial microcompartments self-assemble through specific protein–protein interactions that are typically mediated by conserved protein domains. In this review, we frame our current understanding of carboxysomes in the context of their component protein domains with their inherent function as the ‘building blocks’ of carboxysomes. These building blocks are organized in genetic modules (conserved chromosomal loci) that encode for carboxysomes andmore » ancillary proteins essential for the integration of the organelle with the rest of cellular metabolism. This conceptual framework provides the foundation for ‘plug-and-play’ engineering of carboxysomes as CO 2 fixation modules in a variety of biotechnological applications.« less

  12. SLP-2 negatively modulates mitochondrial sodium-calcium exchange.

    PubMed

    Da Cruz, Sandrine; De Marchi, Umberto; Frieden, Maud; Parone, Philippe A; Martinou, Jean-Claude; Demaurex, Nicolas

    2010-01-01

    Mitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca(2+) transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca(2+) elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na(+) removal or addition of CGP-37157, an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na(+) and Ca(2+) concentration. The rates of mitochondrial Ca(2+) extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca(2+) elevations. The amplitude of cytosolic Ca(2+) elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca(2+) and to shape cytosolic Ca(2+) signals. 2009 Elsevier Ltd. All rights reserved.

  13. Implementation of an e-learning module improves consistency in the histopathological diagnosis of sessile serrated lesions within a nationwide population screening programme.

    PubMed

    IJspeert, Joep E G; Madani, Ariana; Overbeek, Lucy I H; Dekker, Evelien; Nagtegaal, Iris D

    2017-05-01

    Distinguishing premalignant sessile serrated lesions (SSLs) from hyperplastic polyps (HPs) is difficult for pathologists in daily practice. We aimed to evaluate nationwide variability within histopathology laboratories in the frequency of diagnosing an SSL as compared with an HP within the Dutch population-based screening programme for colorectal cancer and to assess the effect of an e-learning module on interlaboratory consistency. Data were retrieved from the Dutch Pathology Registry from the start of the nationwide population screening programme, January 2014, until December 2015. An obligatory e-learning module was implemented among pathologists in October 2014. The ratio between SSL and HP diagnosis was determined per laboratory. Odds ratios (ORs) for the diagnosis of an SSL per laboratory were compared with the laboratory with the median odds (median laboratory), before and after implementation of the e-learning module. In total, 14 997 individuals with 27 879 serrated polyps were included; 6665 (23.9%) were diagnosed as SSLs, and 21 214 as HPs (76.1%). The ratio of diagnosing an SSL ranged from 5% to 47% (median 23%) within 44 laboratories. Half of the laboratories showed a significantly different OR (range 3.47-0.16) for diagnosing an SSL than the median laboratory. Variability decreased after implementation of the e-learning module (P = 0.02). Of all pathology laboratories, 70% became more consistent with the median laboratory after e-learning implementation. We demonstrated substantial interlaboratory variability in the histopathological diagnosis of SSLs, which significantly decreased after implementation of a structured e-learning module. Widespread implementation of education might contribute to more homogeneous practice among pathologists. © 2016 John Wiley & Sons Ltd.

  14. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    Technicians assist as the Orion crew module for Exploration Mission-1 is moved toward the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  15. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    A crane is being prepared for use during move operations of the Orion crew module for Exploration Mission-1 to the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  16. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    Technicians prepare a crane for use during move operations of the Orion crew module for Exploration Mission-1 to the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  17. GDF11 Modulates Ca2+-Dependent Smad2/3 Signaling to Prevent Cardiomyocyte Hypertrophy.

    PubMed

    Duran, Javier; Troncoso, Mayarling Francisca; Lagos, Daniel; Ramos, Sebastian; Marin, Gabriel; Estrada, Manuel

    2018-05-18

    Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β family, has been shown to act as a negative regulator in cardiac hypertrophy. Ca 2+ signaling modulates cardiomyocyte growth; however, the role of Ca 2+ -dependent mechanisms in mediating the effects of GDF11 remains elusive. Here, we found that GDF11 induced intracellular Ca 2+ increases in neonatal rat cardiomyocytes and that this response was blocked by chelating the intracellular Ca 2+ with BAPTA-AM or by pretreatment with inhibitors of the inositol 1,4,5-trisphosphate (IP₃) pathway. Moreover, GDF11 increased the phosphorylation levels and luciferase activity of Smad2/3 in a concentration-dependent manner, and the inhibition of IP₃-dependent Ca 2+ release abolished GDF11-induced Smad2/3 activity. To assess whether GDF11 exerted antihypertrophic effects by modulating Ca 2+ signaling, cardiomyocytes were exposed to hypertrophic agents (100 nM testosterone or 50 μM phenylephrine) for 24 h. Both treatments increased cardiomyocyte size and [³H]-leucine incorporation, and these responses were significantly blunted by pretreatment with GDF11 over 24 h. Moreover, downregulation of Smad2 and Smad3 with siRNA was accompanied by inhibition of the antihypertrophic effects of GDF11. These results suggest that GDF11 modulates Ca 2+ signaling and the Smad2/3 pathway to prevent cardiomyocyte hypertrophy.

  18. Variations of the critical foE-frequency of the ionosphere connected with earthquakes. Evaluation of observations of the vertical sounding station "Tokyo"

    NASA Astrophysics Data System (ADS)

    Liperovskaya, Elena V.; Meister, Claudia-Veronika; Hoffmann, Dieter H. H.; Silina, Alexandra S.

    2016-04-01

    In the present work the critical frequencies foE and foF2 of the ionosphere are considered as possible earthquake precursors. The statistical analysis of the critical frequencies is carried out based on the data of the vertical sounding station (VSS) "Kokubunji" ("Tokyo") (ϕ = 35.7o N, λ = 139.5o E, 1957-1988) obtained every hour. Disturbances are considered on the background of seasonal, geomagnetic as well as 11-years and 27-days Solar variations. Special normalized parameters E and F are introduced, which represent the almost seasonal-independent parts of foE and foF2. Days with high Solar (Wolf number > 100) and geomagnetic (ΣKp > 25) activities are excluded from the analysis. For all data (observed every hour) analysed, no correlations of the normalized parameters E and F are found. One day before the seismic shock, a positive correlation is observed. The superimposed epochs method is used to determine the temporal behaviour of E and F. It is found that E and F decrease one day before the earthquakes provided that the seismic shocks occur at distances 600 < R < 1000 km from the VSS, and that the focus of earthquakes with magnitudes M > 5.5 is situated at depths smaller than 60 km. The reliability of the effect is larger than 98 %. Possible physical mechanisms of the phenomenon are discussed.

  19. CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

    PubMed Central

    Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-01-01

    CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

  20. Microsomal Prostaglandin E2 Synthase-1 Modulates the Response to Vascular Injury

    PubMed Central

    Wang, Miao; Ihida-Stansbury, Kaori; Kothapalli, Devashish; Tamby, Mathieu C.; Yu, Zhou; Chen, Lihong; Grant, Gregory; Cheng, Yan; Lawson, John A.; Assoian, Richard K.; Jones, Peter L.; FitzGerald, Garret A.

    2013-01-01

    Background Microsomal (m) prostaglandin (PG) E2 synthase (S)-1 catalyzes the formation of PGE2 from PGH2, a cyclooxygenase (COX) product that is derived from arachidonic acid. Previous studies in mice suggest that targeting mPGES-1 may be less likely to cause hypertension or thrombosis than COX-2 selective inhibition or deletion in vivo. Indeed, deletion of mPGES-1 retards atherogenesis and angiotensin II-induced aortic aneurysm formation. The role of mPGES-1 in the response to vascular injury is unknown. Methods and Results Mice were subjected to wire injury of the femoral artery. Both neointimal area and vascular stenosis were reduced significantly four weeks after injury in mPGES-1 knock out (KO) mice compared to wild type (WT) controls (65.6±5.7 vs 37.7±5.1×103 pixel area and 70.5±13.4% vs 47.7±17.4%, respectively; p < 0.01). Induction of tenascin C (TN-C) after injury, a pro-proliferative and promigratory extracellular matrix protein, was attenuated in the KOs. Consistent with in vivo rediversion of PG biosynthesis, mPGES-1 deleted vascular smooth muscle cells (VSMC) generated less PGE2, but more PGI2 and expressed reduced TN-C when compared with WT cells. Both suppression of PGE2 and augmentation of PGI2 attenuate TN-C expression, VSMC proliferation and migration in vitro. Conclusions Deletion of mPGES-1 in mice attenuates neointimal hyperplasia after vascular injury, in part by regulating TN-C expression. This raises for consideration the therapeutic potential of mPGES-1 inhibitors as adjuvant therapy for percutaneous coronary intervention. PMID:21282500

  1. Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

    PubMed

    Martins da Fonseca, Caíque Silveira; Pimenta Filho, Adenor Almeida; dos Santos, Bianka Santana; da Silva, César Augusto; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lúcia de Menezes

    2014-01-01

    Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis. Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups. We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat

  2. Critical Thinking Concept Reconstructed

    ERIC Educational Resources Information Center

    Minter, Mary Kennedy

    2010-01-01

    This paper explores the proposition that teaching of critical thinking (CT) should include: (1) identifying and addressing the many environmental variables acting as barriers to our human thinking, i.e., an open system approach, and (2) utilizing the interrelatedness of the CT building blocks, i.e., creative thinking techniques, levels of…

  3. eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing.

    PubMed

    Yuan, Tiezheng; Huang, Xiaoyi; Dittmar, Rachel L; Du, Meijun; Kohli, Manish; Boardman, Lisa; Thibodeau, Stephen N; Wang, Liang

    2014-03-05

    RNA sequencing (RNA-seq) is emerging as a critical approach in biological research. However, its high-throughput advantage is significantly limited by the capacity of bioinformatics tools. The research community urgently needs user-friendly tools to efficiently analyze the complicated data generated by high throughput sequencers. We developed a standalone tool with graphic user interface (GUI)-based analytic modules, known as eRNA. The capacity of performing parallel processing and sample management facilitates large data analyses by maximizing hardware usage and freeing users from tediously handling sequencing data. The module miRNA identification" includes GUIs for raw data reading, adapter removal, sequence alignment, and read counting. The module "mRNA identification" includes GUIs for reference sequences, genome mapping, transcript assembling, and differential expression. The module "Target screening" provides expression profiling analyses and graphic visualization. The module "Self-testing" offers the directory setups, sample management, and a check for third-party package dependency. Integration of other GUIs including Bowtie, miRDeep2, and miRspring extend the program's functionality. eRNA focuses on the common tools required for the mapping and quantification analysis of miRNA-seq and mRNA-seq data. The software package provides an additional choice for scientists who require a user-friendly computing environment and high-throughput capacity for large data analysis. eRNA is available for free download at https://sourceforge.net/projects/erna/?source=directory.

  4. 2016 NREL Photovoltaic Module Reliability Workshop

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

    Kurtz, Sarah

    NREL's Photovoltaic (PV) Module Reliability Workshop (PVMRW) brings together PV reliability experts to share information, leading to the improvement of PV module reliability. Such improvement reduces the cost of solar electricity and promotes investor confidence in the technology - both critical goals for moving PV technologies deeper into the electricity marketplace.

  5. 2015 NREL Photovoltaic Module Reliability Workshops

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

    Kurtz, Sarah

    NREL's Photovoltaic (PV) Module Reliability Workshop (PVMRW) brings together PV reliability experts to share information, leading to the improvement of PV module reliability. Such improvement reduces the cost of solar electricity and promotes investor confidence in the technology--both critical goals for moving PV technologies deeper into the electricity marketplace.

  6. Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules

    PubMed Central

    Maugg, Doris; Eckstein, Gertrud; Baumhoer, Daniel; Nathrath, Michaela; Korsching, Eberhard

    2015-01-01

    Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and

  7. Saturn's E, G, and F rings - Modulated by the plasma sheet?

    NASA Technical Reports Server (NTRS)

    Morfill, G. E.; Gruen, E.; Johnson, T. V.

    1983-01-01

    Saturn's broad E ring, the narrow G ring, and the structured and apparently time-variable F ring(s) contain many micron and submicron-sized particles, which make up the 'visible' component. These rings (or ring systems) are in direct contact with magnetospheric plasma. Fluctuations in the plasma density and/or mean energy, due to magnetospheric and solar wind processes, may induce stochastic charge variations on the dust particles, which in turn lead to an orbit perturbation and spatial diffusion. In addition, Coulomb drag forces may be important, in particular for the E ring. The possibility that electromagnetic effects may play a role in determining the F ring structure and its possible time variations is critically examined. Sputtering of micron-sized dust particles in the E ring by magnetospheric ions yields lifetimes of 100 to 10,000 years. This effect as well as the plasma induced transport processes require an active source for the E ring, probably Enceladus.

  8. Intracavity optically controlled crystal modulators for a CO/sub 2/ laser

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

    Chizhevskii, V.N.; Churakov, V.V.

    1986-06-01

    This paper presents the results of studies of intracavity amplitude modulation of CW CO/sub 2/ laser radiation by its optically controlled absorption on nonequilibrium charge carriers (NCC) in KRS-5, KRS-6, and ZnSe crystals. The fundamental variables which determine the efficiency of such a modulation method are discussed. The radiation from a ruby laser with a 35-nsec pulse width was used to produce the nonequilibrium charge carriers. The variation of the modulation percentage of the intensity vs. excitation level at lambda = 0.6943 ..mu..m is shown for different powers of the CO/sub 2/ laser. The studies attest to the relatively highmore » efficiency of intracavity modulation based on IR radiation absorption by NCC in crystals, where the NCC are generated under the influence of external excitation.« less

  9. The tobacco cembranoid (1S,2E,4S,7E,11E)-2,7,11-cembratriene-4,6-diol as a novel angiogenesis inhibitory lead for the control of breast malignancies.

    PubMed

    Hailat, Mohammad M; Ebrahim, Hassan Y; Mohyeldin, Mohamed M; Goda, Amira A; Siddique, Abu Bakar; El Sayed, Khalid A

    2017-08-01

    (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its 4-epi-analog (2) are diterpene precursors of the key flavor components in most Nicotiana (tobacco) species that purposely degraded during commercial tobacco fermentation. Angiogenesis, recruitment of new blood vessels, is important for tumor growth, survival and metastasis that can be targeted to control cancer. This study shows evidences and potential of the cembranoid 1 as a potent angiogenesis modulator through targeting VEGFR 2 . In silico study suggested favorable docking scores and binding affinity of 1 at the ATP binding pocket of VEGFR 2 . The binding mode of 1 was parallel to the standard FDA-approved antiangiogenic drug sunitinib (4). In vitro, cembranoid 1 significantly reduced the activated VEGFR 2 levels in multiple breast cancer cell lines. Intraperitoneal 40mg/kg, 3X/week treatment of 1 significantly reduced the MDA-MB-231 cells breast tumor size in mice. Immunohistochemistry and Western blotting analysis of the treated mice tumors showed significant downregulation of the vasculogenesis marker CD31 and suppressed activated VEGFR 2 -paxillin-FAK pathway. Matrigel study in Swiss albino mice showed similar trend. The tobacco cembranoid 1 is a potential antiangiogenic lead useful for future use to control breast malignancies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 4-Stage Online Presence Model: Model for Module Design and Delivery Using Web 2.0 Technologies to Facilitate Critical Thinking Skills

    ERIC Educational Resources Information Center

    Goh, WeiWei; Dexter, Barbara; Self, Richard

    2014-01-01

    The main purpose of this paper is to present a conceptual model for the use of web 2.0 online technologies in order to develop and enhance students' critical thinking skills at higher education level. Wiki is chosen as the main focus in this paper. The model integrates Salmon's 5-stage model (Salmon, 2002) with Garrison's Community of Inquiry…

  11. Stirring Up an Elastic Fluid: Critical Viscosity of Xenon-2 (CVX-2)

    NASA Astrophysics Data System (ADS)

    Berg, Robert F.; Moldover, Michael R.; Zimmerli, Gregory A.

    2002-12-01

    Whipped cream stays in place even when turned upside down. Yet it readily flows through the nozzle of a spray can to reach the dessert plate. This demonstrates the phenomenon of shear thinning that is important to many industrial and physical processes. Paints, film emulsions, and other complex solutions that are highly viscous under normal conditions but become thin and flow easily under shear forces. A simple fluid, such as water, does not exhibit shear thinning under normal conditions. Very close to the liquid-vapor critical point, where the distinction between liquid and vapor disappears, the fluid becomes more complex and is predicted to display shear thinning. At the critical point, xenon atoms interact over long distances in a classical model of cooperative phenomena. Physicists rely on this system to learn how long-range order arises. The Critical Viscosity of Xenon Experiment (CVX-2) will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of fluids. Viscosity originates from the interactions of individual molecules. It is so complicated that, except for the simplest gas, it cannot be calculated accurately from theory. Tests with critical fluids can provide key data, but are limited on Earth because critical fluids are highly compressed by gravity. CVX-2 employs a tiny metal screen vibrating between two electrodes in a bath of critical xenon. The vibrations and how they dampen are used to measure viscosity. CVX flew on STS-85 (1997), where it revealed that, close to the critical point, the xenon is partly elastic: it can 'stretch' as well as flow. For STS-107, the hardware has been enhanced to determine if critical xenon is a shear-thinning fluid.

  12. Stirring Up an Elastic Fluid: Critical Viscosity of Xenon-2 (CVX-2)

    NASA Technical Reports Server (NTRS)

    Berg, Robert F.; Moldover, Michael R.; Zimmerli, Gregory A.; Motil, Susan M. (Technical Monitor)

    2002-01-01

    Whipped cream stays in place even when turned upside down. Yet it readily flows through the nozzle of a spray can to reach the dessert plate. This demonstrates the phenomenon of shear thinning that is important to many industrial and physical processes. Paints, film emulsions, and other complex solutions that are highly viscous under normal conditions but become thin and flow easily under shear forces. A simple fluid, such as water, does not exhibit shear thinning under normal conditions. Very close to the liquid-vapor critical point, where the distinction between liquid and vapor disappears, the fluid becomes more complex and is predicted to display shear thinning. At the critical point, xenon atoms interact over long distances in a classical model of cooperative phenomena. Physicists rely on this system to learn how long-range order arises. The Critical Viscosity of Xenon Experiment (CVX-2) will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of fluids. Viscosity originates from the interactions of individual molecules. It is so complicated that, except for the simplest gas, it cannot be calculated accurately from theory. Tests with critical fluids can provide key data, but are limited on Earth because critical fluids are highly compressed by gravity. CVX-2 employs a tiny metal screen vibrating between two electrodes in a bath of critical xenon. The vibrations and how they dampen are used to measure viscosity. CVX flew on STS-85 (1997), where it revealed that, close to the critical point, the xenon is partly elastic: it can 'stretch' as well as flow. For STS-107, the hardware has been enhanced to determine if critical xenon is a shear-thinning fluid.

  13. Nutritional modulation of resistance to infectious diseases.

    PubMed

    Klasing, K C

    1998-08-01

    Dietary characteristics can modulate a bird's susceptibility to infectious challenges and subtle influences due to the level of nutrients or the types of ingredients may at times be of critical importance. This review considers seven mechanisms for nutritional modulation of resistance to infectious disease in poultry. 1) Nutrition may impact the development of the immune system, both in ovo and in the first weeks posthatch. Micronutrient deficiencies that affect developmental events, such as the seeding of lymphoid organs and clonal expansion of lymphocyte clones, can negatively impact the immune system later in life. 2) A substrate role of nutrients is necessary for the immune response so that responding cells can divide and synthesize effector molecules. The quantitative need for nutrients for supporting a normal immune system, as well as the proliferation of leukocytes and the production of antibodies during an infectious challenge, is very small relative to uses for growth or egg production. It is likely that the systemic acute phase response that accompanies most infectious challenges is a more significant consumer of nutrients than the immune system itself. 3) The low concentration of some nutrients (e.g., iron) in body fluids makes them the limiting substrates for the proliferation of invading pathogens and the supply of these nutrients is further limited during the immune response. 4) Some nutrients (e.g., fatty acids and vitamins A, D, and E) have direct regulatory actions on leukocytes by binding to intracellular receptors or by modifying the release of second messengers. 5) The diet may also have indirect regulatory effects that are mediated by the classical endocrine system. 6) Physical and chemical aspects of the diet can modify the populations of microorganisms in the gastrointestinal tract, the capacity of pathogens to attach to enterocytes, and the integrity of the intestinal epithelium.

  14. Comparison of foE and M(3000)F2 variability at Ibadan, Singapore and Slough

    NASA Astrophysics Data System (ADS)

    Somoye, E. O.; Onori, E. O.; Akala, A. O.

    2013-01-01

    The variability, VR, of critical frequency of E-layer, foE, and ionospheric propagation factor, M(3000)F2 at Ibadan (7.4°N, 3.9°E, 6°S dip) is investigated for local time, seasonal and solar cycle variations. Latitudinal influence of these characteristics is sought by comparison with foE VR and M(3000)F2 VR of Slough ( 51.5°N, 359.4°E, 66.5°N dip) in the European sector, and Singapore (1.3°N,103.8°E, 17.6°S dip) in the Asian sector. While the pattern of foE VR is similar to those of other F2 characteristics with characteristic peaks around dawn and dusk, M(3000)F2 VR shows no clear diurnal trend.A lower bound of foE VR is usually 3% while the maximum VR ranges between 8% and13% at post-sunrise and pre-sunset hours at all the epochs, M(3000)F2 VR is however lower during MSA (about 9%) than during LSA and HSA when it is 4% to about 12-14%. Generally, daytime M(3000)F2 VR is greater than that of foE VR by between 5% and 10%. Furthermore, no latitudinal difference is observed in both characteristics during both HSA and MSA. While nighttime M(3000)F2 VR is about half that of nighttime foF2 VR (the critical frequency of F2-layer ) VR, daytime VR of both characteristics are about equal during the three epochs at Ibadan. For Slough, nighttime M(3000)F2 VR and nighttime foF2 VR as well as the daytime VR of both characteristics are about equal. This difference is most likely due to latitudinal effect.

  15. Electronic and structural properties of B i2S e3:Cu

    NASA Astrophysics Data System (ADS)

    Sobczak, Kamil; Strak, Pawel; Kempisty, Pawel; Wolos, Agnieszka; Hruban, Andrzej; Materna, Andrzej; Borysiuk, Jolanta

    2018-04-01

    Electronic and structural properties of B i2S e3 and its extension to copper doped B i2S e3:Cu were studied using combined ab initio simulations and transmission electron microscopy based techniques, including electron energy loss spectroscopy, energy filtered transmission electron microscopy, and energy dispersive x-ray spectroscopy. The stability of the mixed phases was investigated for substitutional and intercalation changes of basic B i2S e3 structure. Four systems were compared: B i2S e3 , structures obtaining by Cu intercalation of the van der Waals gap, by substitution of Bi by Cu in quintuple layers, and C u2Se . The structures were identified and their electronic properties were obtained. Transmission electron microscopy measurements of B i2S e3 and the B i2S e3:Cu system identified the first structure as uniform and the second as composite, consisting of a nonuniform lower-Cu-content matrix and randomly distributed high-Cu-concentration precipitates. Critical comparison of the ab initio and experimental data identified the matrix as having a B i2S e3 dominant part with randomly distributed Cu-intercalated regions having 1Cu-B i2S e3 structure. The precipitates were determined to have 3Cu-B i2S e3 structure.

  16. E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue.

    PubMed

    Lim, Jung Hwa; Shin, Hee Won; Chung, Kyung-Sook; Kim, Nam-Soon; Kim, Ju Hee; Jung, Hong-Ryul; Im, Dong-Soo; Jung, Cho-Rok

    Here, we show that E2-EPF ubiquitin carrier protein (UCP) elongated E3-independent polyubiquitin chains on the lysine residues of von Hippel-Lindau protein (pVHL) and its own lysine residues both in vitro and in vivo. The initiation of the ubiquitin reaction depended on not only Lys11 linkage but also the Lys6, Lys48 and Lys63 residues of ubiquitin, which were involved in polyubiquitin chain formation on UCP itself. UCP self-association occurred through the UBC domain, which also contributed to the interaction with pVHL. The polyubiquitin chains appeared on the N-terminus of UCP in vivo, which indicated that the N-terminus of UCP contains target lysines for polyubiquitination. The Lys76 residue of UCP was the most critical site for auto-ubiquitination, whereas the polyubiquitin chain formation on pVHL occurred on all three of its lysines (Lys159, Lys171 and Lys196). A UCP mutant in which Cys118 was changed to alanine (UCPC118A) did not form a polyubiquitin chain but did strongly accumulate mono- and di-ubiquitin via auto-ubiquitination. Polyubiquitin chain formation required the coordination of Cys95 and Cys118 between two interacting molecules. The mechanism of the polyubiquitin chain reaction of UCP may involve the transfer of ubiquitin from Cys95 to Cys118 by trans-thiolation, with polyubiquitin chains forming at Cys118 by reversible thioester bonding. The polyubiquitin chains are then moved to the lysine residues of the substrate by irreversible isopeptide bonding. During the elongation of the ubiquitin chain, an active Cys118 residue is required in both parts of UCP, namely, the catalytic enzyme and the substrate. In conclusion, UCP possesses not only E2 ubiquitin conjugating enzyme activity but also E3 ubiquitin ligase activity, and Cys118 is critical for polyubiquitin chain formation.

  17. E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue

    PubMed Central

    Lim, Jung Hwa; Shin, Hee Won; Chung, Kyung-Sook; Kim, Nam-Soon; Kim, Ju Hee; Jung, Hong-Ryul; Im, Dong-Soo; Jung, Cho-Rok

    2016-01-01

    Here, we show that E2-EPF ubiquitin carrier protein (UCP) elongated E3-independent polyubiquitin chains on the lysine residues of von Hippel-Lindau protein (pVHL) and its own lysine residues both in vitro and in vivo. The initiation of the ubiquitin reaction depended on not only Lys11 linkage but also the Lys6, Lys48 and Lys63 residues of ubiquitin, which were involved in polyubiquitin chain formation on UCP itself. UCP self-association occurred through the UBC domain, which also contributed to the interaction with pVHL. The polyubiquitin chains appeared on the N-terminus of UCP in vivo, which indicated that the N-terminus of UCP contains target lysines for polyubiquitination. The Lys76 residue of UCP was the most critical site for auto-ubiquitination, whereas the polyubiquitin chain formation on pVHL occurred on all three of its lysines (Lys159, Lys171 and Lys196). A UCP mutant in which Cys118 was changed to alanine (UCPC118A) did not form a polyubiquitin chain but did strongly accumulate mono- and di-ubiquitin via auto-ubiquitination. Polyubiquitin chain formation required the coordination of Cys95 and Cys118 between two interacting molecules. The mechanism of the polyubiquitin chain reaction of UCP may involve the transfer of ubiquitin from Cys95 to Cys118 by trans-thiolation, with polyubiquitin chains forming at Cys118 by reversible thioester bonding. The polyubiquitin chains are then moved to the lysine residues of the substrate by irreversible isopeptide bonding. During the elongation of the ubiquitin chain, an active Cys118 residue is required in both parts of UCP, namely, the catalytic enzyme and the substrate. In conclusion, UCP possesses not only E2 ubiquitin conjugating enzyme activity but also E3 ubiquitin ligase activity, and Cys118 is critical for polyubiquitin chain formation. PMID:27685940

  18. Voltage-sensing phosphatase modulation by a C2 domain.

    PubMed

    Castle, Paul M; Zolman, Kevin D; Kohout, Susy C

    2015-01-01

    The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in

  19. Thermionic modules

    DOEpatents

    King, Donald B.; Sadwick, Laurence P.; Wernsman, Bernard R.

    2002-06-18

    Modules of assembled microminiature thermionic converters (MTCs) having high energy-conversion efficiencies and variable operating temperatures manufactured using MEMS manufacturing techniques including chemical vapor deposition. The MTCs incorporate cathode to anode spacing of about 1 micron or less and use cathode and anode materials having work functions ranging from about 1 eV to about 3 eV. The MTCs also exhibit maximum efficiencies of just under 30%, and thousands of the devices and modules can be fabricated at modest costs.

  20. The Adenovirus E1A C Terminus Suppresses a Delayed Antiviral Response and Modulates RAS Signaling.

    PubMed

    Zemke, Nathan R; Berk, Arnold J

    2017-12-13

    The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p.i. This delayed activation of ISGs required IRF3 and coincided with an ∼10-fold increase in IRF3 from protein stabilization. The induced IRF3 bound to chromatin and localized to the promoters of activated ISGs. While IRF3, STAT1/2, and IRF9 all greatly increased in concentration, there were no corresponding mRNA increases, suggesting that e1a regulates the stabilities of these key activators of innate immune responses, as shown directly for IRF3. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

    PubMed

    Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

    2015-01-15

    Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.

  2. 47 CFR 2.201 - Emission, modulation, and transmission characteristics.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., and transmission characteristics. The following system of designating emission, modulation, and transmission characteristics shall be employed. (a) Emissions are designated according to their classification... characteristics. 2.201 Section 2.201 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY...

  3. 47 CFR 2.201 - Emission, modulation, and transmission characteristics.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., and transmission characteristics. The following system of designating emission, modulation, and transmission characteristics shall be employed. (a) Emissions are designated according to their classification... characteristics. 2.201 Section 2.201 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL FREQUENCY...

  4. Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae

    PubMed Central

    2011-01-01

    Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail. PMID:21489243

  5. Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2.

    PubMed

    Krintel, Christian; Francotte, Pierre; Pickering, Darryl S; Juknaitė, Lina; Pøhlsgaard, Jacob; Olsen, Lars; Frydenvang, Karla; Goffin, Eric; Pirotte, Bernard; Kastrup, Jette S

    2016-06-07

    The 1,2,4-benzothiadiazine 1,1-dioxide type of positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind in a cleft formed by the interface of two neighboring ligand binding domains and act by stabilizing the agonist-bound open-channel conformation. The driving forces behind the binding of these modulators can be significantly altered with only minor substitutions to the parent molecules. In this study, we show that changing the 7-fluorine substituent of modulators BPAM97 (2) and BPAM344 (3) into a hydroxyl group (BPAM557 (4) and BPAM521 (5), respectively), leads to a more favorable binding enthalpy (ΔH, kcal/mol) from -4.9 (2) and -7.5 (3) to -6.2 (4) and -14.5 (5), but also a less favorable binding entropy (-TΔS, kcal/mol) from -2.3 (2) and -1.3 (3) to -0.5 (4) and 4.8 (5). Thus, the dissociation constants (Kd, μM) of 4 (11.2) and 5 (0.16) are similar to those of 2 (5.6) and 3 (0.35). Functionally, 4 and 5 potentiated responses of 10 μM L-glutamate at homomeric rat GluA2(Q)i receptors with EC50 values of 67.3 and 2.45 μM, respectively. The binding mode of 5 was examined with x-ray crystallography, showing that the only change compared to that of earlier compounds was the orientation of Ser-497 pointing toward the hydroxyl group of 5. The favorable enthalpy can be explained by the formation of a hydrogen bond from the side-chain hydroxyl group of Ser-497 to the hydroxyl group of 5, whereas the unfavorable entropy might be due to desolvation effects combined with a conformational restriction of Ser-497 and 5. In summary, this study shows a remarkable example of enthalpy-entropy compensation in drug development accompanied with a likely explanation of the underlying structural mechanism. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Strain-induced dimensionality crossover of precursor modulations in Ni{sub 2}MnGa

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

    Nie, Zhihua, E-mail: zhihua-nie@yahoo.com, E-mail: ydwang@neu.edu.cn; Wang, Yandong, E-mail: zhihua-nie@yahoo.com, E-mail: ydwang@neu.edu.cn; Shang, Shunli

    2015-01-12

    Precursor modulations often occur in functional materials like magnetic shape memory alloys, ferroelectrics, and superconductors. In this letter, we have revealed the underlying mechanism of the precursor modulations in ferromagnetic shape memory alloys Ni{sub 2}MnGa by combining synchrotron-based x-ray diffraction experiments and first-principles phonon calculations. We discovered the precursor modulations along [011] direction can be eliminated with [001] uniaxial loading, while the precursor modulations or premartensite can be totally suppressed by hydrostatic pressure condition. The TA{sub 2} phonon anomaly is sensitive to stress induced lattice strain, and the entire TA{sub 2} branch is stabilized along the directions where precursor modulationsmore » are eliminated by external stress. Our discovery bridges precursor modulations and phonon anomalies, and sheds light on the microscopic mechanism of the two-step superelasticity in precursor martensite.« less

  7. Magic Clusters of MoS2 by Edge S2 Interdimer Spacing Modulation.

    PubMed

    Ryou, Junga; Kim, Yong-Sung

    2018-05-17

    Edge atomic and electronic structures of S-saturated Mo-edge triangular MoS 2 nanoclusters are investigated using density functional theory calculations. The edge electrons described by the S 2 -p x p x π* (S 2 -Π x ) and Mo-d xy orbitals are found to interplay to pin the S 2 -Π x Fermi wavenumber at k F = 2/5 as the nanocluster size increases, and correspondingly, the ×5 Peierls edge S 2 interdimer spacing modulation is induced. For the particular sizes of N = 5 n - 2 and 5 n, where N is the number of Mo atoms at one edge representing the nanocluster size and n is a positive integer, the effective ×5 interdimer spacing modulation stabilizes the nanoclusters, which are identified here to be the magic S-saturated Mo-edge triangular MoS 2 nanoclusters. With the S 2 -Π x Peierls gap, the MoS 2 nanoclusters become far-edge S 2 -Π x semiconducting and subedge Mo-d xy metallic as N → ∞.

  8. Asparatic acid 221 is critical in the calcium-induced modulation of the enzymatic activity of human aminopeptidase A.

    PubMed

    Goto, Yoshikuni; Hattori, Akira; Mizutani, Shigehiko; Tsujimoto, Masafumi

    2007-12-21

    Aminopeptidase A (APA) plays an important role in the regulation of blood pressure by mediating angiotensin II degradation in the renin-angiotensin system. The Ca2+-induced modulation of enzymatic activity is the most characteristic feature of APA among the M1 family of aminopeptidases. In this study, we used site-directed mutagenesis for any residues responsible for the Ca2+ modulation of human APA. Alignment of sequences of the M1 family members led to the identification of Asp-221 as a significant residue of APA among the family members. Replacement of Asp-221 with Asn or Gln resulted in a loss of Ca2+ responsiveness toward synthetic substrates. These enzymes were also unresponsive to Ca2+ when peptide hormones, such as angiotensin II, cholecystokinin-8, neurokinin B, and kallidin, were employed as substrates. These results suggest that the negative charge of Asp-221 is essential for Ca2+ modulation of the enzymatic activity of APA and causes preferential cleavage of acidic amino acid at the N-terminal end of substrate peptides.

  9. Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system

    USDA-ARS?s Scientific Manuscript database

    E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV). E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. Howev...

  10. The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

    PubMed

    Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

    2007-07-01

    We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G(2)/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G(2) checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIalpha protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness.

  11. Project T.E.A.M. (Technical Education Advancement Modules). Introduction to Statistical Process Control.

    ERIC Educational Resources Information Center

    Billings, Paul H.

    This instructional guide, one of a series developed by the Technical Education Advancement Modules (TEAM) project, is a 6-hour introductory module on statistical process control (SPC), designed to develop competencies in the following skill areas: (1) identification of the three classes of SPC use; (2) understanding a process and how it works; (3)…

  12. Development of CO2 laser dispersion interferometer with photoelastic modulator

    NASA Astrophysics Data System (ADS)

    Akiyama, T.; Kawahata, K.; Okajima, S.; Nakayama, K.

    2010-10-01

    A dispersion interferometer is one of the promising methods of the electron density measurement on large and high density fusion devices. This paper describes development of a CO2 laser dispersion interferometer with a photoelastic modulator for phase modulation. In order to make the dispersion interferometer free from variations of the detected intensity, a new phase extraction method is introduced: The phase shift is evaluated from a ratio of amplitudes of the fundamental and the second harmonics of the phase modulation frequency in the detected interference signal. The proof-of-principle experiments demonstrate the feasibility of this method.

  13. Development of CO2 laser dispersion interferometer with photoelastic modulator.

    PubMed

    Akiyama, T; Kawahata, K; Okajima, S; Nakayama, K

    2010-10-01

    A dispersion interferometer is one of the promising methods of the electron density measurement on large and high density fusion devices. This paper describes development of a CO(2) laser dispersion interferometer with a photoelastic modulator for phase modulation. In order to make the dispersion interferometer free from variations of the detected intensity, a new phase extraction method is introduced: The phase shift is evaluated from a ratio of amplitudes of the fundamental and the second harmonics of the phase modulation frequency in the detected interference signal. The proof-of-principle experiments demonstrate the feasibility of this method.

  14. Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation

    PubMed Central

    Tang, Liang; Cheng, Pengle

    2017-01-01

    Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC) is extracted with the periodic boundary condition applied on it. An elastic–plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM) model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM) model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis. PMID:28746390

  15. Homogenized modeling methodology for 18650 lithium-ion battery module under large deformation.

    PubMed

    Tang, Liang; Zhang, Jinjie; Cheng, Pengle

    2017-01-01

    Effective lithium-ion battery module modeling has become a bottleneck for full-size electric vehicle crash safety numerical simulation. Modeling every single cell in detail would be costly. However, computational accuracy could be lost if the module is modeled by using a simple bulk material or rigid body. To solve this critical engineering problem, a general method to establish a computational homogenized model for the cylindrical battery module is proposed. A single battery cell model is developed and validated through radial compression and bending experiments. To analyze the homogenized mechanical properties of the module, a representative unit cell (RUC) is extracted with the periodic boundary condition applied on it. An elastic-plastic constitutive model is established to describe the computational homogenized model for the module. Two typical packing modes, i.e., cubic dense packing and hexagonal packing for the homogenized equivalent battery module (EBM) model, are targeted for validation compression tests, as well as the models with detailed single cell description. Further, the homogenized EBM model is confirmed to agree reasonably well with the detailed battery module (DBM) model for different packing modes with a length scale of up to 15 × 15 cells and 12% deformation where the short circuit takes place. The suggested homogenized model for battery module makes way for battery module and pack safety evaluation for full-size electric vehicle crashworthiness analysis.

  16. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

    PubMed

    Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

    2018-03-30

    Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory

    PubMed Central

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D’Adamio, Luciano

    2015-01-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing – such as PSEN1/2 and ITM2b/BRI2 – cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16– 17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16–17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. PMID:26528887

  18. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

    PubMed

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Structural basis for histone H2B deubiquitination by the SAGA DUB module

    DOE PAGES

    Morgan, Michael T.; Haj-Yahya, Mahmood; Ringel, Alison E.; ...

    2016-02-12

    Monoubiquitinated histone H2B plays multiple roles in transcription activation. H2B is deubiquitinated by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator, which contains a four-protein subcomplex known as the deubiquitinating (DUB) module. In this paper, the crystal structure of the Ubp8/Sgf11/Sus1/Sgf73 DUB module bound to a ubiquitinated nucleosome reveals that the DUB module primarily contacts H2A/H2B, with an arginine cluster on the Sgf11 zinc finger domain docking on the conserved H2A/H2B acidic patch. The Ubp8 catalytic domain mediates additional contacts with H2B, as well as with the conjugated ubiquitin. Finally, we find that the DUB module deubiquitinates H2B both in the context ofmore » the nucleosome and in H2A/H2B dimers complexed with the histone chaperone, FACT, suggesting that SAGA could target H2B at multiple stages of nucleosome disassembly and reassembly during transcription.« less

  20. Comparison of manual scaled and predicted foE and foF1 critical frequencies. Technical report

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

    Gamache, R.R.; Kersey, W.T.

    1990-07-01

    The CCIR and Titheridge foE critical frequency prediction routines were tested by comparison with 1875 manually scaled values. The foF1 critical frequency prediction routine of Millman et al was tested by comparison with 1005 manually scaled values. Plots and statistics of the comparisons are presented and discussed. From the results recommendations are made to help improve autoscaling.

  1. Walking Drosophila align with the e-vector of linearly polarized light through directed modulation of angular acceleration

    PubMed Central

    Velez, Mariel M.; Wernet, Mathias F.; Clark, Damon A.

    2014-01-01

    Understanding the mechanisms that link sensory stimuli to animal behavior is a central challenge in neuroscience. The quantitative description of behavioral responses to defined stimuli has led to a rich understanding of different behavioral strategies in many species. One important navigational cue perceived by many vertebrates and insects is the e-vector orientation of linearly polarized light. Drosophila manifests an innate orientation response to this cue (‘polarotaxis’), aligning its body axis with the e-vector field. We have established a population-based behavioral paradigm for the genetic dissection of neural circuits guiding polarotaxis to both celestial as well as reflected polarized stimuli. However, the behavioral mechanisms by which flies align with a linearly polarized stimulus remain unknown. Here, we present a detailed quantitative description of Drosophila polarotaxis, systematically measuring behavioral parameters that are modulated by the stimulus. We show that angular acceleration is modulated during alignment, and this single parameter may be sufficient for alignment. Furthermore, using monocular deprivation, we show that each eye is necessary for modulating turns in the ipsilateral direction. This analysis lays the foundation for understanding how neural circuits guide these important visual behaviors. PMID:24810784

  2. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    Technicians check a crane that will be used during move operations of the Orion crew module for Exploration Mission-1 to the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  3. Critical Success Factors in Crafting Strategic Architecture for E-Learning at HP University

    ERIC Educational Resources Information Center

    Sharma, Kunal; Pandit, Pallvi; Pandit, Parul

    2011-01-01

    Purpose: The purpose of this paper is to outline the critical success factors for crafting a strategic architecture for e-learning at HP University. Design/methodology/approach: A descriptive survey type of research design was used. An empirical study was conducted on students enrolled with the International Centre for Distance and Open Learning…

  4. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

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

    Kanginakudru, Sriramana, E-mail: skangina@iu.edu; DeSmet, Marsha, E-mail: mdesmet@iupui.edu; Thomas, Yanique, E-mail: ysthomas@umail.iu.edu

    2015-04-15

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reducedmore » viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.« less

  5. A Panel Prototype for the Mu2e Straw Tube Tracker at Fermilab

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

    Lucà, Alessandra

    The Mu2e experiment will search for coherent, neutrino-less conversion of muons into electrons in the Coulomb field of an aluminum nucleus with a sensitivity of four orders of magnitude better than previous experiments. The signature of this process is an electron with energy nearly equal to the muon mass. Mu2e relies on a precision (0.1%) measurement of the outgoing electron momentum to separate signal from background. In order to achieve this goal, Mu2e has chosen a very low-mass straw tracker, made of 20,736 5 mm diameter thin-walled (15more » $$\\mu$$m) Mylar straws, held under tension to avoid the need for supports within the active volume, and arranged in an approximately 3 m long by 0.7 m radius cylinder, operated in vacuum and a 1 T magnetic field. Groups of 96 straws are assembled into modules, called panels. We present the prototype and the assembly procedure for a Mu2e tracker panel built at Fermilab« less

  6. CYP2E1 hydroxylation of aniline involves negative cooperativity.

    PubMed

    Hartman, Jessica H; Knott, Katie; Miller, Grover P

    2014-02-01

    CYP2E1 plays a role in the metabolic activation and elimination of aniline, yet there are conflicting reports on its mechanism of action, and hence relevance, in aniline metabolism. Based on our work with similar compounds, we hypothesized that aniline binds two CYP2E1 sites during metabolism resulting in cooperative reaction kinetics and tested this hypothesis through rigorous in vitro studies. The kinetic profile for recombinant CYP2E1 demonstrated significant negative cooperativity based on a fit of data to the Hill equation (n=0.56). Mechanistically, the data were best explained through a two-binding site cooperative model in which aniline binds with high affinity (K(s)=30 μM) followed by a second weaker binding event (K(ss)=1100 uM) resulting in a threefold increase in the oxidation rate. Binding sites for aniline were confirmed by inhibition studies with 4-methylpyrazole. Inhibitor phenotyping experiments with human liver microsomes validated the central role for CYP2E1 in aniline hydroxylation and indicated minor roles for CYP2A6 and CYP2C9. Importantly, inhibition of minor metabolic pathways resulted in a kinetic profile for microsomal CYP2E1 that replicated the preferred mechanism and parameters observed with the recombinant enzyme. Scaled modeling of in vitro CYP2E1 metabolism of aniline to in vivo clearance, especially at low aniline levels, led to significant deviations from the traditional model based on non-cooperative, Michaelis-Menten kinetics. These findings provide a critical mechanistic perspective on the potential importance of CYP2E1 in the metabolic activation and elimination of aniline as well as the first experimental evidence of a negatively cooperative metabolic reaction catalyzed by CYP2E1. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Estradiol-17beta, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium.

    PubMed

    Waclawik, Agnieszka; Jabbour, Henry N; Blitek, Agnieszka; Ziecik, Adam J

    2009-08-01

    Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin estradiol-17beta (E(2)) (PGE(2)). We hypothesized that embryo signal, E(2), and PGE(2) modulate expression of key enzymes in PG synthesis: PG-endoperoxide synthase-2 (PTGS2), microsomal PGE synthase (mPGES-1), PGF synthase (PGFS), and PG 9-ketoreductase (CBR1) as well as PGE(2) receptor (PTGER2 and -4) expression and signaling within the endometrium. We determined the site of action of PGE(2) in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n = 6) on d 11-12 of the estrous cycle were treated with vehicle (control), PGE(2) (100 nM), E(2) (1-100 nm), or phorbol 12-myristate 13-acetate (100 nm, positive control). E(2) increased PGE(2) secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E(2) decreased PGFS and CBR1 protein expression. E(2) also stimulated PTGER2 but not PTGER4 protein content. PGE(2) enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1, and PTGER2 protein expression. PGE(2) had no effect on PGFS, CBR1, and PTGER4 expression and PGF(2alpha) release. Treatment of endometrial tissue with PGE(2) increased cAMP production. Cotreatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE(2)-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium and was significantly up-regulated on d 11-12 of pregnancy. Our results suggest that E(2) prevents luteolysis through enzymatic modification of PG synthesis and that E(2), PGE(2), and endometrial PTGER2 are involved in a PGE(2) positive feedback loop in porcine endometrium.

  8. Preservice Teachers' Critical Thinking Dispositions and Web 2.0 Competencies

    ERIC Educational Resources Information Center

    Sendag, Serkan; Erol, Osman; Sezgin, Sezan; Dulkadir, Nihal

    2015-01-01

    The aim of this study was to investigate the associations between preservice teachers' Web 2.0 competencies and their critical thinking disposition (CTD). The study employed an associational research design using California Critical Thinking Disposition-Inventory (CCTD-I) and a Web 2.0 competency questionnaire including items related to Web 2.0…

  9. KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis.

    PubMed

    Wang, Ling-Yu; Hung, Chiu-Lien; Chen, Yun-Ru; Yang, Joy C; Wang, Junjian; Campbell, Mel; Izumiya, Yoshihiro; Chen, Hong-Wu; Wang, Wen-Ching; Ann, David K; Kung, Hsing-Jien

    2016-09-13

    The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Critical Success Factors for E-Learning in Developing Countries: A Comparative Analysis between ICT Experts and Faculty

    ERIC Educational Resources Information Center

    Bhuasiri, Wannasiri; Xaymoungkhoun, Oudone; Zo, Hangjung; Rho, Jae Jeung; Ciganek, Andrew P.

    2012-01-01

    This study identifies the critical success factors that influence the acceptance of e-learning systems in developing countries. E-learning is a popular mode of delivering educational materials in higher education by universities throughout the world. This study identifies multiple factors that influence the success of e-learning systems from the…

  11. Critical de Broglie wavelength in superconductors

    NASA Astrophysics Data System (ADS)

    Talantsev, E. F.

    2018-03-01

    There are growing numbers of experimental evidences that the self-field critical currents, Jc(sf,T), are a new instructive tool to investigate fundamental properties of superconductors ranging from atomically thin films [M. Liao et al., Nat. Phys. 6 (2018), https://doi.org/10.1038/s41567-017-0031-6; E. F. Talantsev et al., 2D Mater. 4 (2017) 025072; A. Fete et al., Appl. Phys. Lett. 109 (2016) 192601] to millimeter-scale samples [E. F. Talantsev et al., Sci. Rep. 7 (2017) 10010]. The basic empirical equation which quantitatively accurately described experimental Jc(sf,T) was proposed by Talantsev and Tallon [Nat. Commun. 6 (2015) 7820] and it was the relevant critical field (i.e. thermodynamic field, Bc, for type-I and lower critical field, Bc1, for type-II superconductors) divided by the London penetration depth, λL. In this paper, we report new findings relating to this empirical equation. It is that the critical wavelength of the de Broglie wave, λdB,c, of the superconducting charge carrier which within a numerical pre-factor is equal to the largest of two characteristic lengths of Ginzburg-Landau theory, i.e. the coherence length, ξ, for type-I superconductors or the London penetration depth, λL, for type-II superconductors. We also formulate a microscopic criterion for the onset of dissipative transport current flow: ps ṡ 2ṡλL ln(1+2ṡ(λL ξ )) ≥ 1 2 ṡ ( h 2π), where ps is the charge carrier momentum, h is Planck’s constant and the inequality sign “ <” is reserved for the dissipation-free flow.

  12. Quantum critical spin-2 chain with emergent SU(3) symmetry.

    PubMed

    Chen, Pochung; Xue, Zhi-Long; McCulloch, I P; Chung, Ming-Chiang; Huang, Chao-Chun; Yip, S-K

    2015-04-10

    We study the quantum critical phase of an SU(2) symmetric spin-2 chain obtained from spin-2 bosons in a one-dimensional lattice. We obtain the scaling of the finite-size energies and entanglement entropy by exact diagonalization and density-matrix renormalization group methods. From the numerical results of the energy spectra, central charge, and scaling dimension we identify the conformal field theory describing the whole critical phase to be the SU(3)_{1} Wess-Zumino-Witten model. We find that, while the Hamiltonian is only SU(2) invariant, in this critical phase there is an emergent SU(3) symmetry in the thermodynamic limit.

  13. Beam Propagator for Weather Radars, Modules 1 and 2

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

    Ortega, Edwin Campos

    2013-10-08

    This program simulates the beam propagation of weather radar pulses under particular and realistic atmospheric conditions (without using the assumption of standard refraction conditions). It consists of two modules: radiosondings_refract_index_many.pro (MAIN MODULE) beam_propagation_function.pro(EXTERNAL FUNCTION) FOR THE MAIN MODULE, THE CODE DOES OUTPUT--INTO A FILE--THE BEAM HEIGHT AS A FUNCTION OF RANGE. THE RADIOSONDE INPUT FILES SHOULD BE ALREADY AVAILABLE BY THE USER. FOR EXAMPLE, RADIOSONDE OBSERVATION FILES CAN BE OBTAINED AT: RADIOSONDE OBSERVATIONS DOWNLOADED AT "http://weather.uwyo.edu/upperair/soounding.html" OR "http://jervis.pyr.ec.gc.ca" THE EXTERNAL FUNCTION DOES THE ACTUAL COMPUTATION OF BEAM PROPAGATION. IT INCLUDES CONDITIONS OF ANOMALOUS PROPAGATION AND NEGATIVE ELEVATION ANGLES. THE EQUATIONSmore » USED HERE WERE DERIVED BY EDWIN CAMPOS, BASED ON THE SNELL-DESCARTES LAW OF REFRACTION, CONSIDERING THE EARTH CURVATURE. THE PROGRAM REQUIRES A COMPILER FOR THE INTERACTIVE DATA LANGUAGE (IDL). DESCRIPTION AND VALIDATION DETAILS HAVE BEEN PUBLISHED IN THE PEER-REVIEWED SCIENTIFIC LITERATURE, AS FOLLOWS: Campos E. 2012. Estimating weather radar coverage over complex terrain, pp.26-32, peer reviewed, in Weather Radar and Hydrology, edited by Moore RJ, Cole SJ and Illingworth AJ. International Association of Hydrological Sciences (IAHS) Press, IAHS Publ. 351. ISBN 978-1-907161-26-1.« less

  14. The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells.

    PubMed

    Laan, Lisa C; Williams, Andrew R; Stavenhagen, Kathrin; Giera, Martin; Kooij, Gijs; Vlasakov, Iliyan; Kalay, Hakan; Kringel, Helene; Nejsum, Peter; Thamsborg, Stig M; Wuhrer, Manfred; Dijkstra, Christine D; Cummings, Richard D; van Die, Irma

    2017-02-01

    Clinical trials have shown that administration of the nematode Trichuris suis can be beneficial in treating various immune disorders. To provide insight into the mechanisms by which this worm suppresses inflammatory responses, an active component was purified from T. suis soluble products (TsSPs) that suppress---- TNF and IL-12 secretion from LPS-activated human dendritic cells (DCs). Analysis by liquid chromatography tandem mass spectrometry identified this compound as prostaglandin (PG)E2. The purified compound showed similar properties compared with TsSPs and commercial PGE2 in modulating LPS-induced expression of many cytokines and chemokines and in modulating Rab7B and P2RX7 expression in human DCs. Furthermore, the TsSP-induced reduction of TNF secretion from DCs is reversed by receptor antagonists for EP2 and EP4, indicating PGE2 action. T. suis secretes extremely high amounts of PGE2 (45-90 ng/mg protein) within their excretory/secretory products but few related lipid mediators as established by metabololipidomic analysis. Culture of T. suis with several cyclooxygenase (COX) inhibitors that inhibit mammalian prostaglandin synthesis affected the worm's motility but did not inhibit PGE2 secretion, suggesting that the worms can synthesize PGE2 via a COX-independent pathway. We conclude that T. suis secretes PGE2 to suppress proinflammatory responses in human DCs, thereby modulating the host's immune response.-Laan, L. C., Williams, A. R., Stavenhagen, K., Giera, M., Kooij, G., Vlasakov, I., Kalay, H., Kringel, H., Nejsum, P., Thamsborg, S. M., Wuhrer, M., Dijkstra, C. D., Cummings, R. D., van Die, I. The whipworm (Trichuris suis) secretes prostaglandin E2 to suppress proinflammatory properties in human dendritic cells. © FASEB.

  15. Doubling of the Critical Current Density of 2G-YBCO Coated Conductors through proton irradiation

    NASA Astrophysics Data System (ADS)

    Welp, Ulrich; Jia, Ying; Kwok, Wai-Kwong; Rupich, Marty; Fleshler, Steven; Kayani, Asfghar

    2013-03-01

    We report on magnetization and transport measurements of the critical current density of commercial 2G YBCO coated conductors before and after proton irradiation. The samples were irradiated along the c-axis with 4 MeV protons to a fluence of 1.5x1016 p/cm2. We find that at temperatures below 50 K, proton irradiation increases Jc by a factor of 2 in low fields and increases up to 2.5 in fields of 7 T. At 77 K, proton irradiation is less effective in enhancing the critical current. Doubling of Jc in fields of several Tesla and at temperatures below 50 K will be highly beneficial for applications of coated conductors in rotating machinery, generators and magnet coils. - Work supported by the US DoE-BES funded Energy Frontier Research Center (YJ), and by Department of Energy, Office of Science, Office of Basic Energy Sciences (UW, WKK), under Contract No. DE-AC02-06CH11357.

  16. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

    PubMed

    Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

    2009-12-01

    Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

  17. Modulating lignin in plants

    DOEpatents

    Apuya, Nestor; Bobzin, Steven Craig; Okamuro, Jack; Zhang, Ke

    2013-01-29

    Materials and methods for modulating (e.g., increasing or decreasing) lignin content in plants are disclosed. For example, nucleic acids encoding lignin-modulating polypeptides are disclosed as well as methods for using such nucleic acids to generate transgenic plants having a modulated lignin content.

  18. Critical behavior of quasi-two-dimensional semiconducting ferromagnet Cr 2 Ge 2 Te 6

    DOE PAGES

    Liu, Yu; Petrovic, C.

    2017-08-03

    Some critical properties of the single-crystalline semiconducting ferromagnet Cr 2 Ge 2 Te 6 were investigated by bulk dc magnetization around the paramagnetic to ferromagnetic phase transition. Critical exponents β = 0.200 ± 0.003 with a critical temperature T c = 62.65 ± 0.07 K and γ = 1.28 ± 0.03 with T c = 62.75 ± 0.06 K are obtained by the Kouvel-Fisher method whereas δ = 7.96 ± 0.01 is obtained by a critical isotherm analysis at T c = 62.7 K. These critical exponents obey the Widom scaling relation δ = 1 + γ / β ,more » indicating self-consistency of the obtained values. Furthermore, with these critical exponents the isotherm M ( H ) curves below and above the critical temperatures collapse into two independent universal branches, obeying the single scaling equation m = f ± ( h ) , where m and h are renormalized magnetization and field, respectively. The determined exponents match well with those calculated from the results of the renormalization group approach for a two-dimensional Ising system coupled with a long-range interaction between spins decaying as J ( r ) ≈ r - ( d + σ ) with σ = 1.52 .« less

  19. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors.

    PubMed

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-02-01

    Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. E1R was tested for sigma receptor binding activity in a [³H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca²⁺ concentration ([Ca²⁺](i)) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca²⁺](i) increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. © 2013 The British Pharmacological Society.

  20. Experimental Studies on the Flammability and Fire Hazards of Photovoltaic Modules

    PubMed Central

    Yang, Hong-Yun; Zhou, Xiao-Dong; Yang, Li-Zhong; Zhang, Tao-Lin

    2015-01-01

    Many of the photovoltaic (PV) systems on buildings are of sufficiently high voltages, with potential to cause or promote fires. However, research about photovoltaic fires is insufficient. This paper focuses on the flammability and fire hazards of photovoltaic modules. Bench-scale experiments based on polycrystalline silicon PV modules have been conducted using a cone calorimeter. Several parameters including ignition time (tig), mass loss, heat release rate (HRR), carbon monoxide (CO) and carbon dioxide (CO2) concentration, were investigated. The fire behaviours, fire hazards and toxicity of gases released by PV modules are assessed based on experimental results. The results show that PV modules under tests are inflammable with the critical heat flux of 26 kW/m2. This work will lead to better understanding on photovoltaic fires and how to help authorities determine the appropriate fire safety provisions for controlling photovoltaic fires. PMID:28793434

  1. Layering Networked and Symphonic Selves: A Critical Role for e-Portfolios in Employability through Integrative Learning

    ERIC Educational Resources Information Center

    Cambridge, Darren

    2008-01-01

    Purpose: E-portfolios, which document and facilitate learning and performance, have recently attracted interest in the USA, UK, and Europe as means to increase employability and support lifelong learning. This article aims to critically examine these objectives in order to guide the future e-portfolio practice. Design/methodology/approach: Social…

  2. Characterization of a novel RNA-binding region of eIF4GI critical for ribosomal scanning

    PubMed Central

    Prévôt, Déborah; Décimo, Didier; Herbreteau, Cécile H.; Roux, Florence; Garin, Jérôme; Darlix, Jean-Luc; Ohlmann, Théophile

    2003-01-01

    The eukaryotic translation initiation factor eIF4GI binds several proteins and acts as a scaffold to promote preinitiation complex formation on the mRNA molecule (48S). Following mRNA attachment this complex scans along the messenger in a 5′ to 3′ direction until it locates and recognizes the initiation start codon. By using a combination of retroviral and picornaviral proteases (HIV-2 and L respectively) in the reticulocyte lysate system, we have characterized a 40 amino acid (aa) region of eIF4GI (aa 642–681) that exhibits general RNA-binding properties. Removal of this domain by proteolytic processing followed by translational assays showed virtually no inhibition of internal ribosome entry on the encephalomyocarditis virus, but resulted in drastic impairment of ribosome scanning as demonstrated by studying poliovirus and foot-and-mouth disease virus translation. Based on these findings, we propose that this 40 aa motif of eIF4GI is critical for ribosome scanning. PMID:12682023

  3. InGaAs monolithic interconnected modules (MIM)

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

    Fatemi, N.S.; Jenkins, P.P.; Weizer, V.G.

    1997-12-31

    A monolithic interconnected module (MIM) structure has been developed for thermophotovoltaic (TPV) applications. The MIM device consists of many individual InGaAs cells series-connected on a single semi-insulating (S.I.) InP substrate. An infrared (IR) back surface reflector (BSR), placed on the rear surface of the substrate, returns the unused portion of the TPV radiator output spectrum back to the emitter for recycling, thereby providing for high system efficiencies. Also, the use of a BSR obviates the need to use a separate filtering element. As a result, MIMs are exposed to the entire emitter output, thereby maximizing output power density. MIMs withmore » an active area of 1 x 1-cm were comprised of 15 cells monolithically connected in series. Both lattice-matched and lattice-mismatched InGaAs/InP devices were produced, with bandgaps of 0.74 and 0.55 eV, respectively. The 0.74-eV modules demonstrated an open-circuit voltage (Voc) of 6.158 V and a fill factor of 74.2% at a short-circuit current (Jsc) of 842 mA/cm{sup 2}, under flashlamp testing. The 0.55-eV modules demonstrated a Voc of 4.849 V and a fill factor of 57.8% at a Jsc of 3.87 A/cm{sup 2}. IR reflectance measurements (i.e., {lambda} > 2 {micro}m) of these devices indicated a reflectivity of {ge} 83%. Latest electrical and optical performance results for the MIMs will be presented.« less

  4. Fluoridation and Defluoridation. Training Module 2.230.2.77.

    ERIC Educational Resources Information Center

    McMullen, L. D.

    This document is an instructional module package prepared in objective form for use by an instructor familiar with fluoridation and fluoride feeding equipment. Enclosed are objectives, an instructor guide, student handouts and transparency masters. The module considers the principles and purposes of fluoridation, methods of feeding fluoride,…

  5. Single mode CO2 laser frequency modulation up to 350 MHz

    NASA Technical Reports Server (NTRS)

    Leeb, W. R.; Peruso, C. J.

    1977-01-01

    Experiments on internal frequency modulation (FM) of a CO2 laser showed no limitation of FM by the linewidth. However, distortions in the form of strong enhancement of sideband amplitude arise for frequencies equal to the cavity resonant frequencies, most pronounced if the modulator is positioned near a cavity mirror.

  6. The challenges of classical swine fever control: modified live and E2 subunit vaccines.

    PubMed

    Huang, Yu-Liang; Deng, Ming-Chung; Wang, Fun-In; Huang, Chin-Cheng; Chang, Chia-Yi

    2014-01-22

    Classical swine fever (CSF) is an economically important, highly contagious disease of swine worldwide. CSF is caused by classical swine fever virus (CSFV), and domestic pigs and wild boars are its only natural hosts. The two main strategies used to control CSF epidemic are systematic prophylactic vaccination and a non-vaccination stamping-out policy. This review compares the protective efficacy of the routinely used modified live vaccine (MLV) and E2 subunit vaccines and summarizes the factors that influence the efficacy of the vaccines and the challenges that both vaccines face to CSF control. Although MLV provide earlier and more complete protection than E2 subunit vaccines, it has the drawback of not allowing differentiation between infected and vaccinated animals (DIVA). The marker vaccine of E2 protein with companion discriminatory test to detect antibodies against E(rns) allows DIVA and is a promising strategy for future control and eradication of CSF. Maternal derived antibody (MDA) is the critical factor in impairing the efficacy of both MLV and E2 subunit vaccines, so the well-designed vaccination programs of sows and piglets should be considered together. Because of the antigen variation among various genotypes of CSFV, antibodies raised by either MLV or subunit vaccine neutralize genotypically homologous strains better than heterologous ones. However, although this is not a major concern for MLV as the induced immune responses can protect pigs against the challenge of various genotypes of CSFVs, it is critical for E2 subunit vaccines. It is thus necessary to evaluate whether the E2 subunit vaccine can completely protect against the current prevalent strains in the field. An ideal new generation of vaccine should be able to maintain the high protective efficiency of MLV and overcome the problem of antigenic variations while allowing for DIVA. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Synthesis of the thermoelectric nanopowder recovered from the used thermoelectric modules.

    PubMed

    Lee, Kun-Jae; Jin, Yun-Ho; Kong, Man-Sik

    2014-10-01

    We fabricated the thermoelectric powder using the used thermoelectric modules in a vehicle. As a starting material, the used thermoelectric modules were collected and separated to substrate, electrode, solder, and thermoelectric parts by a thermal process. The separation process was performed in a wet process at the critical temperature. The solder in the module was the neighbor part of the thermoelectric material with the lowest melting temperature in the module. We focused on the thermal property of the solder to separate the thermoelectric chips in the module. After the separation process, we prepared the pure thermoelectric material by the chemical etching for an impurity removal. Also the thermoelectric nanopowder was fabricated by a chemical reduction reaction using the recycled thermoelectric materials. The recovered nanopowder was confirmed to the phase of bismuth telluride (Bi2Te3) with the particle size of -15 nm.

  8. Residual stress and damage-induced critical fracture on CO2 laser treated fused silica

    NASA Astrophysics Data System (ADS)

    Matthews, M. J.; Stolken, J. S.; Vignes, R. M.; Norton, M. A.; Yang, S.; Cooke, J. D.; Guss, G. M.; Adams, J. J.

    2009-10-01

    Localized damage repair and polishing of silica-based optics using mid- and far-IR CO2 lasers has been shown to be an effective method for increasing optical damage threshold in the UV. However, it is known that CO2 laser heating of silicate surfaces can lead to a level of residual stress capable of causing critical fracture either during or after laser treatment. Sufficient control of the surface temperature as a function of time and position is therefore required to limit this residual stress to an acceptable level to avoid critical fracture. In this work we present the results of 351 nm, 3ns Gaussian damage growth experiments within regions of varying residual stress caused by prior CO2 laser exposures. Thermally stressed regions were non-destructively characterized using polarimetry and confocal Raman microscopy to measure the stress induced birefringence and fictive temperature respectively. For 1~40s square pulse CO2 laser exposures created over 0.5-1.25kW/cm2 with a 1-3mm 1/e2 diameter beam (Tmax~1500-3000K), the critical damage site size leading to fracture increases weakly with peak temperature, but shows a stronger dependence on cooling rate, as predicted by finite element hydrodynamics simulations. Confocal micro-Raman was used to probe structural changes to the glass over different thermal histories and indicated a maximum fictive temperature of 1900K for Tmax>=2000K. The effect of cooling rate on fictive temperature caused by CO2 laser heating are consistent with finite element calculations based on a Tool-Narayanaswamy relaxation model.

  9. Basic Trickling Filters. Training Module 2.110.2.77.

    ERIC Educational Resources Information Center

    Layton, Ronald F.

    This document is an instructional module package prepared in objective form for use by an instructor familiar with operation and maintenance of a trickling filter wastewater treatment system. Included are objectives, instructor guides, student handouts and transparency masters. This is the first level of a three module series and considers the…

  10. Basic Activated Sludge. Training Module 2.115.2.77.

    ERIC Educational Resources Information Center

    Kirkwood Community Coll., Cedar Rapids, IA.

    This document is an instructional module package prepared in objective form for use by an instructor familiar with operation of activated sludge wastewater treatment plants. Included are objectives, instructor guides, student handouts, and transparency masters. This is the first of a three module series and considers definition of terms, design…

  11. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Eldridge, Sandy; Guo, Liang; Mussio, Jodie; Furniss, Mike; Hamre, John; Davis, Myrtle

    2014-10-01

    Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are being used as an in vitro model system in cardiac biology and in drug discovery (e.g., cardiotoxicity testing). Qualification of these cells for use in mechanistic investigations will require detailed evaluations of cardiomyocyte signaling pathways and cellular responses. ErbB signaling and the ligand neuregulin play critical roles in survival and functional integrity of cardiac myocytes. As such, we sought to characterize the expression and activity of the ErbB family of receptors. Antibody microarray analysis performed on cell lysates derived from maturing hiPSC-CMs detected expression of ∼570 signaling proteins. EGFR/ErbB1, HER2/ErbB2, and ErbB4, but not ErbB3 receptors, of the epidermal growth factor receptor family were confirmed by Western blot. Activation of ErbB signaling by neuregulin-1β (NRG, a natural ligand for ErbB4) and its modulation by trastuzumab (a monoclonal anti-ErbB2 antibody) and lapatinib (a small molecule ErbB2 tyrosine kinase inhibitor) were evaluated through assessing phosphorylation of AKT and Erk1/2, two major downstream kinases of ErbB signaling, using nanofluidic proteomic immunoassay. Downregulation of ErbB2 expression by siRNA silencing attenuated NRG-induced AKT and Erk1/2 phosphorylation. Activation of ErbB signaling with NRG, or inhibition with trastuzumab, alleviated or aggravated doxorubicin-induced cardiomyocyte damage, respectively, as assessed by a real-time cellular impedance analysis and ATP measurement. Collectively, these results support the expanded use of hiPSC-CMs to examine mechanisms of cardiotoxicity and support the value of using these cells in early assessments of cardiotoxicity or efficacy. Published by Oxford University Press on behalf of Toxicological Sciences 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. eRNA: a graphic user interface-based tool optimized for large data analysis from high-throughput RNA sequencing

    PubMed Central

    2014-01-01

    Background RNA sequencing (RNA-seq) is emerging as a critical approach in biological research. However, its high-throughput advantage is significantly limited by the capacity of bioinformatics tools. The research community urgently needs user-friendly tools to efficiently analyze the complicated data generated by high throughput sequencers. Results We developed a standalone tool with graphic user interface (GUI)-based analytic modules, known as eRNA. The capacity of performing parallel processing and sample management facilitates large data analyses by maximizing hardware usage and freeing users from tediously handling sequencing data. The module miRNA identification” includes GUIs for raw data reading, adapter removal, sequence alignment, and read counting. The module “mRNA identification” includes GUIs for reference sequences, genome mapping, transcript assembling, and differential expression. The module “Target screening” provides expression profiling analyses and graphic visualization. The module “Self-testing” offers the directory setups, sample management, and a check for third-party package dependency. Integration of other GUIs including Bowtie, miRDeep2, and miRspring extend the program’s functionality. Conclusions eRNA focuses on the common tools required for the mapping and quantification analysis of miRNA-seq and mRNA-seq data. The software package provides an additional choice for scientists who require a user-friendly computing environment and high-throughput capacity for large data analysis. eRNA is available for free download at https://sourceforge.net/projects/erna/?source=directory. PMID:24593312

  13. ANTIGENIC MODULATION

    PubMed Central

    Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

    1968-01-01

    Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

  14. Plan for Your Professional Development. Module LT-E-3 of Category E--Professional and Staff Development. Competency-Based Vocational Education Administrator Module Series.

    ERIC Educational Resources Information Center

    Puleo, Nancy F.; And Others

    This module, one in a series of competency-based administrator instructional packages, focuses on a specific competency that vocational education administrators need to be successful in the area of professional and staff development. The purpose of the module is to help administrators to analyze their professional needs and to devise and implement…

  15. Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors.

    PubMed

    Lam, E W; Glassford, J; van der Sman, J; Banerji, L; Pizzey, A R; Shaun, N; Thomas, B; Klaus, G G

    1999-10-01

    Since signals via CD40 and the B cell receptor are known to synergize to induce B cell activation, we have analyzed the pocket protein/E2F complexes in mouse B lymphocytes following stimulation by anti-IgM, anti-CD40, alone or together. We find that E2F4 and DP1 form the predominant E2F heterodimers in the G0 and G1 phases of the cell cycle, complexed with hypophosphorylated p130. During late G1 and S phase this complex is replaced by at least three different E2F complexes, one of which is an E2F complex containing p107 or pRB as well as two "free" E2F complexes consisting of E2F4/DP1 and E2F1-3/DP1. These effects were mirrored by the levels and phosphorylation status of the three pocket proteins. We also observed an increase in electrophoretic mobility of DP1 and E2F4 as B cells progressed from G0 into early G1, resulting from their dephosphorylation. This is known to correlate with a decrease in DNA binding capacity of these proteins and could also be important for derepression of genes negatively regulated through E2F sites in their promoters. These results therefore indicate that the pRB/E2F pathway integrates proliferative signals emanating from the sIgM and CD40 receptors.

  16. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

    PubMed

    Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

    2006-10-01

    The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

  17. Size, weight, and power reduction of mercury cadmium telluride infrared detection modules

    NASA Astrophysics Data System (ADS)

    Breiter, Rainer; Ihle, Tobias; Wendler, Joachim C.; Lutz, Holger; Rutzinger, Stefan; Schallenberg, Timo; Hofmann, Karl C.; Ziegler, Johann

    2011-06-01

    Application requirements driving present IR technology development activities are improved capability to detect and identify a threat as well as the need to reduce size weight and power consumption (SWaP) of thermal sights. In addition to the development of 3rd Gen IR modules providing dual-band or dual-color capability, AIM is focused on IR FPAs with reduced pitch and high operating temperature for SWaP reduction. State-of-the-art MCT technology allows AIM the production of mid-wave infrared (MWIR) detectors operating at temperatures exceeding 120 K without any need to sacrifice the 5-μm cut-off wavelength. These FPAs allow manufacturing of low cost IR modules with minimum size, weight, and power for state-of-the-art high performance IR systems. AIM has realized full TV format MCT 640×512 mid-wave and long-wave IR detection modules with a 15-μm pitch to meet the requirements of critical military applications like thermal weapon sights or thermal imagers in unmanned aerial vehicles applications. In typical configurations like an F/4.6 cold shield for the 640×512 MWIR module an noise equivalent temperature difference (NETD) <25 mK @ 5 ms integration time is achieved, while the long-wavelength infrared (LWIR) modules achieve an NETD <38 mK @ F/2 and 180 μs integration time. For the LWIR modules, FPAs with a cut-off up to 10 μm have been realized. The modules are available either with different integral rotary cooler configurations for portable applications that require minimum cooling power or a new split linear cooler providing long lifetime with a mean time to failure (MTTF) > 20000, e.g., for warning sensors in 24/7 operation. The modules are available with optional image processing electronics providing nonuniformity correction and further image processing for a complete IR imaging solution. The latest results and performance of those modules and their applications are presented.

  18. Word Criticality Analysis. MOS: 91B. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-09-01

    I 7 AD-A116 535 ARMY TRAINING DEVELOPMENTS INST FORT MONROE VA F/G 5/9 I WORD CRITICALITY ANALYSIS. MOSS 9111. SKILL LEVELS I a 2.(U) I SEP 81 A A...FORT MONROE, VIRGINIA 23651 ELC -~. JUL a Word Criticality Analysis NOS: 913 Skill Levels 1 & 2 PREPARED BY: OPERATIONS DIV, DPFO Cory if CSPIUS ATO...flI. upO"? NUMbER- 0VACCESSION INO a. RCISPIENT’S CATALOG NUMBER 14. TITLE tand 8.begel) S. TYPE OP REPORT & PERIOD COVERED Word Criticality Analysis Vl

  19. Critical behaviour in DOPC/DPPC/cholesterol mixtures: static (2)H NMR line shapes near the critical point.

    PubMed

    Davis, James H; Schmidt, Miranda L

    2014-05-06

    Static (2)H NMR spectroscopy is used to study the critical behavior of mixtures of 1,2-dioleoyl-phosphatidylcholine/1,2-dipalmitoyl-phosphatidylcholine (DPPC)/cholesterol in molar proportion 37.5:37.5:25 using either chain perdeuterated DPPC-d62 or chain methyl deuterated DPPC-d6. The temperature dependence of the first moment of the (2)H spectrum of the sample made with DPPC-d62 and of the quadrupolar splittings of the chain-methyl-labeled DPPC-d6 sample are directly related to the temperature dependence of the critical order parameter η, which scales as [Formula: see text] near the critical temperature. Analysis of the data reveals that for the chain perdeuterated sample, the value of Tc is 301.51 ± 0.1 K, and that of the critical exponent, βc = 0.391 ± 0.02. The line shape analysis of the methyl labeled (d6) sample gives Tc = 303.74 ± 0.07 K and βc = 0.338 ± 0.009. These values obtained for βc are in good agreement with the predictions of a three-dimensional Ising model. The difference in critical temperature between the two samples having nominally the same molar composition arises because of the lowering of the phase transition temperature that occurs due to the perdeuteration of the DPPC. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    PubMed

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  1. Function Specifications for the A-7E Function Driver Module.

    DTIC Science & Technology

    1981-11-27

    Computer interface specifications (HEN181). The services and values provided by the Shared Services module are accurately described in the Shared Services Module...None$) FD.7.l.3.1 FD.7.1.7.1 5517a FD.App3 -5 Appendix 3 Event List (Alphabetical) Events Signalled by other Shared Services submodules @F( ABSCI+ip az...the Shared Services and Device Interface modules. Al; Answer this question for each table that appears in the function driver specification being

  2. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

    PubMed

    Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

    2009-05-01

    E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

  3. The DoE method as an efficient tool for modeling the behavior of monocrystalline Si-PV module

    NASA Astrophysics Data System (ADS)

    Kessaissia, Fatma Zohra; Zegaoui, Abdallah; Boutoubat, Mohamed; Allouache, Hadj; Aillerie, Michel; Charles, Jean-Pierre

    2018-05-01

    The objective of this paper is to apply the Design of Experiments (DoE) method to study and to obtain a predictive model of any marketed monocrystalline photovoltaic (mc-PV) module. This technique allows us to have a mathematical model that represents the predicted responses depending upon input factors and experimental data. Therefore, the DoE model for characterization and modeling of mc-PV module behavior can be obtained by just performing a set of experimental trials. The DoE model of the mc-PV panel evaluates the predictive maximum power, as a function of irradiation and temperature in a bounded domain of study for inputs. For the mc-PV panel, the predictive model for both one level and two levels were developed taking into account both influences of the main effect and the interactive effects on the considered factors. The DoE method is then implemented by developing a code under Matlab software. The code allows us to simulate, characterize, and validate the predictive model of the mc-PV panel. The calculated results were compared to the experimental data, errors were estimated, and an accurate validation of the predictive models was evaluated by the surface response. Finally, we conclude that the predictive models reproduce the experimental trials and are defined within a good accuracy.

  4. Insights into the mechanism of human papillomavirus E2-induced procaspase-8 activation and cell death

    NASA Astrophysics Data System (ADS)

    Singh, Nitu; Senapati, Sanjib; Bose, Kakoli

    2016-02-01

    High-risk human papillomavirus (HR-HPV) E2 protein, the master regulator of viral life cycle, induces apoptosis of host cell that is independent of its virus-associated regulatory functions. E2 protein of HR-HPV18 has been found to be involved in novel FADD-independent activation of caspase-8, however, the molecular basis of this unique non-death-fold E2-mediated apoptosis is poorly understood. Here, with an interdisciplinary approach that involves in silico, mutational, biochemical and biophysical probes, we dissected and characterized the E2-procasapse-8 binding interface. Our data demonstrate direct non-homotypic interaction of HPV18 E2 transactivation domain (TAD) with α2/α5 helices of procaspase-8 death effector domain-B (DED-B). The observed interaction mimics the homotypic DED-DED complexes, wherein the conserved hydrophobic motif of procaspase-8 DED-B (F122/L123) occupies a groove between α2/α3 helices of E2 TAD. This interaction possibly drives DED oligomerization leading to caspase-8 activation and subsequent cell death. Furthermore, our data establish a model for E2-induced apoptosis in HR-HPV types and provide important clues for designing E2 analogs that might modulate procaspase-8 activation and hence apoptosis.

  5. Ultra-high modulation depth exceeding 2,400% in optically controlled topological surface plasmons

    PubMed Central

    Sim, Sangwan; Jang, Houk; Koirala, Nikesh; Brahlek, Matthew; Moon, Jisoo; Sung, Ji Ho; Park, Jun; Cha, Soonyoung; Oh, Seongshik; Jo, Moon-Ho; Ahn, Jong-Hyun; Choi, Hyunyong

    2015-01-01

    Modulating light via coherent charge oscillations in solids is the subject of intense research topics in opto-plasmonics. Although a variety of methods are proposed to increase such modulation efficiency, one central challenge is to achieve a high modulation depth (defined by a ratio of extinction with/without light) under small photon-flux injection, which becomes a fundamental trade-off issue both in metals and semiconductors. Here, by fabricating simple micro-ribbon arrays of topological insulator Bi2Se3, we report an unprecedentedly large modulation depth of 2,400% at 1.5 THz with very low optical fluence of 45 μJ cm−2. This was possible, first because the extinction spectrum is nearly zero due to the Fano-like plasmon–phonon-destructive interference, thereby contributing an extremely small denominator to the extinction ratio. Second, the numerator of the extinction ratio is markedly increased due to the photoinduced formation of massive two-dimensional electron gas below the topological surface states, which is another contributor to the ultra-high modulation depth. PMID:26514372

  6. Criticality in epidemiology

    NASA Astrophysics Data System (ADS)

    Stollenwerk, Nico; Jansen, Vincent A. A.

    For a long time criticality has been considered in epidemiological models. We review the body of theory developed over the last twenty five years for the simplest models. It is at first glance difficult to imagine that an epidemiological system operates at a very fine tuned critical state as opposed to any other parameter region. However, the advent of self-organized criticality has given hints in how to interpret large fluctuations observed in many natural systems including epidemiological systems. We show some scenarios where criticality has been observed (e.g., measles under vaccination) and where evolution towards a critical state can explain fluctuations (e.g., meningococcal disease.)

  7. Voltage-sensing phosphatase modulation by a C2 domain

    PubMed Central

    Castle, Paul M.; Zolman, Kevin D.; Kohout, Susy C.

    2015-01-01

    The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in

  8. Detecting critical state before phase transition of complex systems by hidden Markov model

    NASA Astrophysics Data System (ADS)

    Liu, Rui; Chen, Pei; Li, Yongjun; Chen, Luonan

    Identifying the critical state or pre-transition state just before the occurrence of a phase transition is a challenging task, because the state of the system may show little apparent change before this critical transition during the gradual parameter variations. Such dynamics of phase transition is generally composed of three stages, i.e., before-transition state, pre-transition state, and after-transition state, which can be considered as three different Markov processes. Thus, based on this dynamical feature, we present a novel computational method, i.e., hidden Markov model (HMM), to detect the switching point of the two Markov processes from the before-transition state (a stationary Markov process) to the pre-transition state (a time-varying Markov process), thereby identifying the pre-transition state or early-warning signals of the phase transition. To validate the effectiveness, we apply this method to detect the signals of the imminent phase transitions of complex systems based on the simulated datasets, and further identify the pre-transition states as well as their critical modules for three real datasets, i.e., the acute lung injury triggered by phosgene inhalation, MCF-7 human breast cancer caused by heregulin, and HCV-induced dysplasia and hepatocellular carcinoma.

  9. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes

    NASA Astrophysics Data System (ADS)

    Lu, Xiaolong; Malley, Konstantin R.; Brenner, Caitlin C.; Koroleva, Olga; Korolev, Sergey; Downes, Brian P.

    2016-08-01

    Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2~Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s.

  10. The Ubiquitin-Conjugating Enzyme E2-EPF Is Overexpressed in Primary Breast Cancer and Modulates Sensitivity to Topoisomerase II Inhibition1

    PubMed Central

    Tedesco, Donato; Zhang, Jianhuan; Trinh, Lan; Lalehzadeh, Guita; Meisner, Rene; Yamaguchi, Ken D; Ruderman, Daniel L; Dinter, Harald; Zajchowski, Deborah A

    2007-01-01

    We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER- MDA-MB-231 or MDA-MB-453 breast cancer cells. Because E2-EPF protein levels were elevated during the G2/M phase of the cell cycle and because E2-EPF mRNA in tumor specimens was frequently coexpressed with genes involved in cell cycle control, spindle assembly, and mitotic surveillance, the possibility that E2-EPF might have a function in the cellular response to agents that induce a G2 checkpoint or an M checkpoint was investigated. E2-EPF knockdown sensitized HeLa cells to the topoisomerase (topo) II inhibitors etoposide and doxorubicin and also increased topo IIα protein levels. These data suggest that combined administration of topo II-directed drugs and E2-EPF inhibitors may enhance their clinical effectiveness. PMID:17710163

  11. Modifications modulate anticodon loop dynamics and codon recognition of E. coli tRNA(Arg1,2).

    PubMed

    Cantara, William A; Bilbille, Yann; Kim, Jia; Kaiser, Rob; Leszczyńska, Grażyna; Malkiewicz, Andrzej; Agris, Paul F

    2012-03-02

    Three of six arginine codons are read by two tRNA(Arg) isoacceptors in Escherichia coli. The anticodon stem and loop of these isoacceptors (ASL(Arg1,2)) differs only in that the position 32 cytidine of tRNA(Arg1) is posttranscriptionally modified to 2-thiocytidine (s(2)C(32)). The tRNA(Arg1,2) are also modified at positions 34 (inosine, I(34)) and 37 (2-methyladenosine, m(2)A(37)). To investigate the roles of modifications in the structure and function, we analyzed six ASL(Arg1,2) constructs differing in their array of modifications by spectroscopy and codon binding assays. Thermal denaturation and circular dichroism spectroscopy indicated that modifications contribute thermodynamic and base stacking properties, resulting in more order but less stability. NMR-derived structures of the ASL(Arg1,2) showed that the solution structures of the ASLs were nearly identical. Surprisingly, none possessed the U-turn conformation required for effective codon binding on the ribosome. Yet, all ASL(Arg1,2) constructs efficiently bound the cognate CGU codon. Three ASLs with I(34) were able to decode CGC, whereas only the singly modified ASL(Arg1,2)(ICG) with I(34) was able to decode CGA. The dissociation constants for all codon bindings were physiologically relevant (0.4-1.4 μM). However, with the introduction of s(2)C(32) or m(2)A(37) to ASL(Arg1,2)(ICG), the maximum amount of ASL bound to CGU and CGC was significantly reduced. These results suggest that, by allowing loop flexibility, the modifications modulate the conformation of the ASL(Arg1,2), which takes one structure free in solution and two others when bound to the cognate arginyl-tRNA synthetase or to codons on the ribosome where modifications reduce or restrict binding to specific codons. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. The Prion Protein Modulates A-type K+ Currents Mediated by Kv4.2 Complexes through Dipeptidyl Aminopeptidase-like Protein 6*

    PubMed Central

    Mercer, Robert C. C.; Ma, Li; Watts, Joel C.; Strome, Robert; Wohlgemuth, Serene; Yang, Jing; Cashman, Neil R.; Coulthart, Michael B.; Schmitt-Ulms, Gerold; Jhamandas, Jack H.; Westaway, David

    2013-01-01

    Widely expressed in the adult central nervous system, the cellular prion protein (PrPC) is implicated in a variety of processes, including neuronal excitability. Dipeptidyl aminopeptidase-like protein 6 (DPP6) was first identified as a PrPC interactor using in vivo formaldehyde cross-linking of wild type (WT) mouse brain. This finding was confirmed in three cell lines and, because DPP6 directs the functional assembly of K+ channels, we assessed the impact of WT and mutant PrPC upon Kv4.2-based cell surface macromolecular complexes. Whereas a Gerstmann-Sträussler-Scheinker disease version of PrP with eight extra octarepeats was a loss of function both for complex formation and for modulation of Kv4.2 channels, WT PrPC, in a DPP6-dependent manner, modulated Kv4.2 channel properties, causing an increase in peak amplitude, a rightward shift of the voltage-dependent steady-state inactivation curve, a slower inactivation, and a faster recovery from steady-state inactivation. Thus, the net impact of wt PrPC was one of enhancement, which plays a critical role in the down-regulation of neuronal membrane excitability and is associated with a decreased susceptibility to seizures. Insofar as previous work has established a requirement for WT PrPC in the Aβ-dependent modulation of excitability in cholinergic basal forebrain neurons, our findings implicate PrPC regulation of Kv4.2 channels as a mechanism contributing to the effects of oligomeric Aβ upon neuronal excitability and viability. PMID:24225951

  13. Advanced modulation technology development for earth station demodulator applications. Coded modulation system development

    NASA Technical Reports Server (NTRS)

    Miller, Susan P.; Kappes, J. Mark; Layer, David H.; Johnson, Peter N.

    1990-01-01

    A jointly optimized coded modulation system is described which was designed, built, and tested by COMSAT Laboratories for NASA LeRC which provides a bandwidth efficiency of 2 bits/s/Hz at an information rate of 160 Mbit/s. A high speed rate 8/9 encoder with a Viterbi decoder and an Octal PSK modem are used to achieve this. The BER performance is approximately 1 dB from the theoretically calculated value for this system at a BER of 5 E-7 under nominal conditions. The system operates in burst mode for downlink applications and tests have demonstrated very little degradation in performance with frequency and level offset. Unique word miss rate measurements were conducted which demonstrate reliable acquisition at low values of Eb/No. Codec self tests have verified the performance of this subsystem in a stand alone mode. The codec is capable of operation at a 200 Mbit/s information rate as demonstrated using a codec test set which introduces noise digitally. The measured performance is within 0.2 dB of the computer simulated predictions. A gate array implementation of the most time critical element of the high speed Viterbi decoder was completed. This gate array add-compare-select chip significantly reduces the power consumption and improves the manufacturability of the decoder. This chip has general application in the implementation of high speed Viterbi decoders.

  14. Node 2 and Japanese Experimental Module (JEM) In Space Station Processing Facility

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Lining the walls of the Space Station Processing Facility at the Kennedy Space Center (KSC) are the launch awaiting U.S. Node 2 (lower left). and the first pressurized module of the Japanese Experimental Module (JEM) (upper right), named 'Kibo' (Hope). Node 2, the 'utility hub' and second of three connectors between International Space Station (ISS) modules, was built in the Torino, Italy facility of Alenia Spazio, an International contractor based in Rome. Japan's major contribution to the station, the JEM, was built by the Space Development Agency of Japan (NASDA) at the Tsukuba Space Center near Tokyo and will expand research capabilities aboard the station. Both were part of an agreement between NASA and the European Space Agency (ESA). The Node 2 will be the next pressurized module installed on the Station. Once the Japanese and European laboratories are attached to it, the resulting roomier Station will expand from the equivalent space of a 3-bedroom house to a 5-bedroom house. The Marshall Space Center in Huntsville, Alabama manages the Node program for NASA.

  15. Money talks: neural substrate of modulation of fairness by monetary incentives

    PubMed Central

    Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Yang, Liu-Qing; Li, Shu

    2014-01-01

    A unique feature of the human species is compliance with social norms, e.g., fairness, even though this normative decision means curbing self-interest. However, sometimes people prefer to pursue wealth at the expense of moral goodness. Specifically, deviations from a fairness-related normative choice have been observed in the presence of a high monetary incentive. The neural mechanism underlying this deviation from the fairness-related normative choice has yet to be determined. In order to address this issue, using functional magnetic resonance imaging we employed an ultimatum game (UG) paradigm in which fairness and a proposed monetary amount were orthogonally varied. We found evidence for a significant modulation by the proposed amount on fairness in the right lateral prefrontal cortex (PFC) and the bilateral insular cortices. Additionally, the insular subregions showed dissociable modulation patterns. Inter-individual differences in the modulation effects in the left inferior frontal gyrus (IFG) accounted for inter-individual differences in the behavioral modulation effect as measured by the rejection rate, supporting the concept that the PFC plays a critical role in making fairness-related normative decisions in a social interaction condition. Our findings provide neural evidence for the modulation of fairness by monetary incentives as well as accounting for inter-individual differences. PMID:24834034

  16. Testing the interaction between analytical modules: an example with Roundup Ready® soybean line GTS 40-3-2

    PubMed Central

    2010-01-01

    Background The modular approach to analysis of genetically modified organisms (GMOs) relies on the independence of the modules combined (i.e. DNA extraction and GM quantification). The validity of this assumption has to be proved on the basis of specific performance criteria. Results An experiment was conducted using, as a reference, the validated quantitative real-time polymerase chain reaction (PCR) module for detection of glyphosate-tolerant Roundup Ready® GM soybean (RRS). Different DNA extraction modules (CTAB, Wizard and Dellaporta), were used to extract DNA from different food/feed matrices (feed, biscuit and certified reference material [CRM 1%]) containing the target of the real-time PCR module used for validation. Purity and structural integrity (absence of inhibition) were used as basic criteria that a DNA extraction module must satisfy in order to provide suitable template DNA for quantitative real-time (RT) PCR-based GMO analysis. When performance criteria were applied (removal of non-compliant DNA extracts), the independence of GMO quantification from the extraction method and matrix was statistically proved, except in the case of Wizard applied to biscuit. A fuzzy logic-based procedure also confirmed the relatively poor performance of the Wizard/biscuit combination. Conclusions For RRS, this study recognises that modularity can be generally accepted, with the limitation of avoiding combining highly processed material (i.e. biscuit) with a magnetic-beads system (i.e. Wizard). PMID:20687918

  17. MATRYOSHKA-R (RBO-3-2) radiation suite in service module (SM)

    NASA Image and Video Library

    2009-03-18

    ISS018-E-040992 (18 March 2009) --- Cosmonaut Yury Lonchakov, Expedition 18 flight engineer, works with the European Matroshka-R Phantom experiment in the Zvezda Service Module of the International Space Station while Space Shuttle Discovery (STS-119) remains docked with the station. Matroshka, the name for the traditional Russian set of nestling dolls, is an antroph-amorphous model of a human torso designed for radiation studies.

  18. Solution structure of the Big domain from Streptococcus pneumoniae reveals a novel Ca2+-binding module

    PubMed Central

    Wang, Tao; Zhang, Jiahai; Zhang, Xuecheng; Xu, Chao; Tu, Xiaoming

    2013-01-01

    Streptococcus pneumoniae is a pathogen causing acute respiratory infection, otitis media and some other severe diseases in human. In this study, the solution structure of a bacterial immunoglobulin-like (Big) domain from a putative S. pneumoniae surface protein SP0498 was determined by NMR spectroscopy. SP0498 Big domain adopts an eight-β-strand barrel-like fold, which is different in some aspects from the two-sheet sandwich-like fold of the canonical Ig-like domains. Intriguingly, we identified that the SP0498 Big domain was a Ca2+ binding domain. The structure of the Big domain is different from those of the well known Ca2+ binding domains, therefore revealing a novel Ca2+-binding module. Furthermore, we identified the critical residues responsible for the binding to Ca2+. We are the first to report the interactions between the Big domain and Ca2+ in terms of structure, suggesting an important role of the Big domain in many essential calcium-dependent cellular processes such as pathogenesis. PMID:23326635

  19. 43 CFR 1610.7-2 - Designation of areas of critical environmental concern.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Designation of areas of critical..., PROGRAMMING, BUDGETING Resource Management Planning § 1610.7-2 Designation of areas of critical environmental concern. Areas having potential for Areas of Critical Environmental Concern (ACEC) designation and...

  20. Cell Size and Growth Rate Are Modulated by TORC2-Dependent Signals.

    PubMed

    Lucena, Rafael; Alcaide-Gavilán, Maria; Schubert, Katherine; He, Maybo; Domnauer, Matthew G; Marquer, Catherine; Klose, Christian; Surma, Michal A; Kellogg, Douglas R

    2018-01-22

    The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling. TORC2-dependent control of ceramide signaling strongly influences both cell size and growth rate. Thus, cells that cannot make ceramides fail to modulate their growth rate or size in response to changes in nutrients. PP2A associated with the Rts1 regulatory subunit (PP2A Rts1 ) is embedded in a feedback loop that controls TORC2 signaling and helps set the level of TORC2 signaling to match nutrient availability. Together, the data suggest a model in which growth rate and cell size are mechanistically linked by ceramide-dependent signals arising from the TORC2 network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception

    PubMed Central

    Baumgarten, Thomas J.; Königs, Sara; Schnitzler, Alfons; Lange, Joachim

    2017-01-01

    Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13–18 Hz). This can be compellingly explained by a model of discrete perceptual cycles. PMID:28276493

  2. Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception.

    PubMed

    Baumgarten, Thomas J; Königs, Sara; Schnitzler, Alfons; Lange, Joachim

    2017-03-09

    Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13-18 Hz). This can be compellingly explained by a model of discrete perceptual cycles.

  3. Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

    PubMed

    Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

    2014-07-10

    Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

  4. Resveratrol regulates hyperglycemia-induced modulations in experimental diabetic animal model.

    PubMed

    Rehman, Kanwal; Saeed, Kiran; Munawar, Syeda Mehak; Akash, Muhammad Sajid Hamid

    2018-06-01

    Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium. The results of present study indicate the RSV (P < 0.001) alone and/or in combination with Vit-E (P < 0.001) exhibited a highly significant therapeutic potentials by ameliorating the glycemia-induced modulations. Moreover, we also found that RSV in combination with Vit-E also exhibited a better therapeutic effects when compared with that of MF (P < 0.001) and Vit-E (P < 0.05), respectively. Hence, we conclude that RSV alone and/or in combination with Vit-E exhibit its significant therapeutic potentials against hyperglycemia-induced modulations in experimental diabetic animal model and may be one of the most exciting prospect for future treatment of T2DM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Introduction to Reactor Statics Modules, RS-1. Nuclear Engineering Computer Modules.

    ERIC Educational Resources Information Center

    Edlund, Milton C.

    The nine Reactor Statics Modules are designed to introduce students to the use of numerical methods and digital computers for calculation of neutron flux distributions in space and energy which are needed to calculate criticality, power distribution, and fuel burn-up for both slow neutron and fast neutron fission reactors. The diffusion…

  6. SU-E-T-508: End to End Testing of a Prototype Eclipse Module for Planning Modulated Arc Therapy On the Siemens Platform

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

    Huang, L; Sarkar, V; Spiessens, S

    2014-06-01

    Purpose: The latest clinical implementation of the Siemens Artiste linac allows for delivery of modulated arcs (mARC) using full-field flattening filter free (FFF) photon beams. The maximum doserate of 2000 MU/min is well suited for high dose treatments such as SBRT. We tested and report on the performance of a prototype Eclipse TPS module supporting mARC capability on the Artiste platform. Method: our spine SBRT patients originally treated with 12/13 field static-gantry IMRT (SGIMRT) were chosen for this study. These plans were designed to satisfy RTOG0631 guidelines with a prescription of 16Gy in a single fraction. The cases were re-plannedmore » as mARC plans in the prototype Eclipse module using the 7MV FFF beam and required to satisfy RTOG0631 requirements. All plans were transferred from Eclipse, delivered on a Siemens Artiste linac and dose-validated using the Delta4 system. Results: All treatment plans were straightforwardly developed, in timely fashion, without challenge or inefficiency using the prototype module. Due to the limited number of segments in a single arc, mARC plans required 2-3 full arcs to yield plan quality comparable to SGIMRT plans containing over 250 total segments. The average (3%/3mm) gamma pass-rate for all arcs was 98.5±1.1%, thus demonstrating both excellent dose prediction by the AAA dose algorithm and excellent delivery fidelity. Mean delivery times for the mARC plans(10.5±1.7min) were 50-70% lower than the SGIMRT plans(26±2min), with both delivered at 2000 MU/min. Conclusion: A prototype Eclipse module capable of planning for Burst Mode modulated arc delivery on the Artiste platform has been tested and found to perform efficiently and accurately for treatment plan development and delivered-dose prediction. Further investigation of more treatment sites is being carried out and data will be presented.« less

  7. Flexible programmable logic module

    DOEpatents

    Robertson, Perry J.; Hutchinson, Robert L.; Pierson, Lyndon G.

    2001-01-01

    The circuit module of this invention is a VME board containing a plurality of programmable logic devices (PLDs), a controlled impedance clock tree, and interconnecting buses. The PLDs are arranged to permit systolic processing of a problem by offering wide data buses and a plurality of processing nodes. The board contains a clock reference and clock distribution tree that can drive each of the PLDs with two critically timed clock references. External clock references can be used to drive additional circuit modules all operating from the same synchronous clock reference.

  8. (e,2e) and (Î3,2e) Processes: Open and Closed Questions

    NASA Astrophysics Data System (ADS)

    An important breakthrough has been achieved recently in the description of (e,2e) and (Î3,2e) processes with the development of new ab-initio theories: the external complex scaling theory (ECS), the time dependent close coupling theory (TDCC), and the hyperspherical R-matrix theory with semiclassical outgoing waves (HRM-SOW). The principles of these various theories are summarized, their relations are considered, and their achievements are discussed with respect to the available experimental data regarding electron impact ionization of H and photo double ionization of He. Possible directions for future work are outlined.

  9. SUMOylation pathway alteration coupled with downregulation of SUMO E2 enzyme at mucosal epithelium modulates inflammation in inflammatory bowel disease

    PubMed Central

    Mustfa, Salman Ahmad; Singh, Mukesh; Suhail, Aamir; Mohapatra, Gayatree; Verma, Smriti; Chakravorty, Debangana; Rana, Sarika; Rampal, Ritika; Dhar, Atika; Saha, Sudipto; Ahuja, Vineet

    2017-01-01

    Post-translational modification pathways such as SUMOylation are integral to all cellular processes and tissue homeostasis. We investigated the possible involvement of SUMOylation in the epithelial signalling in Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD). Initially in a murine model of IBD, induced by dextran–sulfate–sodium (DSS mice), we observed inflammation accompanied by a lowering of global SUMOylation of colonic epithelium. The observed SUMOylation alteration was due to a decrease in the sole SUMO E2 enzyme (Ubc9). Mass-spectrometric analysis revealed the existence of a distinct SUMOylome (SUMO-conjugated proteome) in DSS mice with alteration of key cellular regulators, including master kinase Akt1. Knocking-down of Ubc9 in epithelial cells resulted in dramatic activation of inflammatory gene expression, a phenomenon that acted via reduction in Akt1 and its SUMOylated form. Importantly, a strong decrease in Ubc9 and Akt1 was also seen in endoscopic biopsy samples (N = 66) of human CD and UC patients. Furthermore, patients with maximum disease indices were always accompanied by severely lowered Ubc9 or SUMOylated-Akt1. Mucosal tissues with severely compromised Ubc9 function displayed higher levels of pro-inflammatory cytokines and compromised wound-healing markers. Thus, our results reveal an important and previously undescribed role for the SUMOylation pathway involving Ubc9 and Akt1 in modulation of epithelial inflammatory signalling in IBD. PMID:28659381

  10. Orion Crew Module Move

    NASA Image and Video Library

    2017-11-17

    Technicians in clean-room suits attach a crane to the Orion crew module for Exploration Mission-1 for its move to the thermal chamber in the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. Orion will be lifted out of a test stand and lowered onto another stand to for the move. The crew module will undergo a thermal cycle test to assess the workmanship of critical hardware and structural locations. The test also demonstrates crew module subsystem operations in a thermally stressing environment to confirm no damage or anomalous hardware conditions as a result of the test. The Orion spacecraft will launch atop NASA's Space Launch System rocket on its first uncrewed integrated flight.

  11. Christmas Tree in Cupola module

    NASA Image and Video Library

    2015-12-25

    ISS046e002700 (12/25/2015) --- Happy Holiday in space. The crew of Expedition 46 decorated the International Space Station’s Cupola module, a 360-degree series of windows that provides a stunning view of Earth for observations, while also containing the primary controls for the Canadarm2 robotic arm.

  12. "To Break Asunder along the Lesions of Race". The Critical Race Theory of W.E.B. Du Bois

    ERIC Educational Resources Information Center

    Rashid, Kamau

    2011-01-01

    In addition to its beginnings within legal scholarship, Critical Race Theory (CRT) is intimately aligned with the long tradition of African American social critique, which sought to interrogate the intractable nature of racism and White supremacy. Within this intellectual tradition, the works of W.E.B. Du Bois are of critical significance. Du…

  13. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    PubMed Central

    Sidrauski, Carmela; Tsai, Jordan C; Kampmann, Martin; Hearn, Brian R; Vedantham, Punitha; Jaishankar, Priyadarshini; Sokabe, Masaaki; Mendez, Aaron S; Newton, Billy W; Tang, Edward L; Verschueren, Erik; Johnson, Jeffrey R; Krogan, Nevan J; Fraser, Christopher S; Weissman, Jonathan S; Renslo, Adam R; Walter, Peter

    2015-01-01

    The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now report that ISRIB is an activator of eIF2B. Our reporter-based shRNA screen revealed an eIF2B requirement for ISRIB activity. Our results define ISRIB as a symmetric molecule, show ISRIB-mediated stabilization of activated eIF2B dimers, and suggest that eIF2B4 (δ-subunit) contributes to the ISRIB binding site. We also developed new ISRIB analogs, improving its EC50 to 600 pM in cell culture. By modulating eIF2B function, ISRIB promises to be an invaluable tool in proof-of-principle studies aiming to ameliorate cognitive defects resulting from neurodegenerative diseases. DOI: http://dx.doi.org/10.7554/eLife.07314.001 PMID:25875391

  14. Word Criticality Analysis. MOS: 05C. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-09-01

    selected by subject matter/job experts knowledgeable in their NOS. The vocabulary set used as the basis for critical word analysis was the Vord...reports completed last (i.e., dated Jan-Mar 82). 3. Word Criticality Index: The following 5 point rating scale was used by a team of up to 3 subject...r- V, w-. U =* IV - .0~~~~~9 IN’ N .1 0 0f 4rlfC f U’.*.ffi" 9.~ ~ ’ r. L . VN 0, m 4’ f’l M 0 (.f, rnV 0.i3 C.. ~,’ efl CG if r 0.9-p C an SIN W’i I

  15. (BNL/DoE-hyped) ``Self-Organized-Criticality'' (SOC) is Merely Newton's(1687) Third Law of Motion F = ma REdiscovery: LONG PRE-``Bak''!!!

    NASA Astrophysics Data System (ADS)

    Bak, P. R. E.; Newton, I.; Siegel, Edward Carl-Ludwig

    2011-03-01

    "Bak"/BNL/DoE "self-organized-criticality"(SOC) usual BNL/DoE media-hype P.R spin-doctoring "show-biz" "Bush-waaa-...-aaah!!!" is manifestly-demonstrated in two distinct ways to be nothing but Newton's Third Law of Motion F = ma REdiscovery!!! PHYSICS: (1687) cross-multiplied F = ma rewritten as 1/m = a/F = OUTPUT/INPUT = EFFECT/ CAUSE = inverse-mass mechanical-susceptibility = X ("w "); X ("w ") (F.-D. theorem-equivalence /proportionality) P("w ") "noise" power-spectrum; E w ; and E (any/all media upper-limiting-speeds) m. Thus: w E m; inversion yields: 1/w 1 /E 1 /m a/F = X ("w ") P("w "); hence: F = ma dual/inverse-integral-transform is "'SOC"'s" P(w) 1 / w (1) !!! ; "PURE"-MATHS: F = ma double-integral time-series s(t) = [vot + (1/2) at (2) ] inverse/dual-integral-transform formally defines power-spectrum: P (w) = S { s (t) e [ - (iORnoi) wt ] } dt = S { [ vot + (1 / 2) at 2) ] e [ - (iORnoi) wt ] } dt = voS { te [ - (iORnoi) wt ] } dt + (1 / 2) S { [ a = / = a (t) ] e [ - (iORnoi) wt) } dt = vo (d / dw) Delta (w) + (1 / 2) [ a = / = a (t) ] (d / dw) (2) Delta (w) = vo / w (0) + (1 / 2) [ a = / = a (t) ] / w 1 : ifa = 0 , then P(w) 1 / w 0 , VS . ifa = / = a (t) = / = 0 , then P(w) 1 /w; = by physics: ``SOC'' RE-expresses F = ma!!!: ``just `a tad' late/tardy'' REdiscovery of F=ma: LONG PRE-"Bak"!!!

  16. Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway.

    PubMed

    Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying; Cai, Hui

    2015-05-15

    Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs.

  17. Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway

    PubMed Central

    Feng, Xiuyan; Zhang, Yiqian; Shao, Ningjun; Wang, Yanhui; Zhuang, Zhizhi; Wu, Ping; Lee, Matthew J.; Liu, Yingli; Wang, Xiaonan; Zhuang, Jieqiu; Delpire, Eric; Gu, Dingying

    2015-01-01

    Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in maintaining blood pressure. Aldosterone is known to modulate NCC abundance. Previous studies reported that dietary salts modulated NCC abundance through either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine-rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To exclude the influence of SPAK signaling pathway on the role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we investigated the effects of dietary salt changes and aldosterone on NCC abundance in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet significantly increased total NCC abundance while reducing ERK1/2 phosphorylation, whereas high-salt diet decreased total NCC while increasing ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression, an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and reversed the aldosterone-mediated increments of NCC partly by increasing NCC ubiquitination. Therefore, these data suggest that aldosterone modulates NCC abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal pathway in SPAK KO mice and part of the effects of dietary salt changes may be mediated by aldosterone in the DCTs. PMID:25761881

  18. Sorcin modulation of Ca2+ sparks in rat vascular smooth muscle cells

    PubMed Central

    Rueda, Angélica; Song, Ming; Toro, Ligia; Stefani, Enrico; Valdivia, Héctor H

    2006-01-01

    Spontaneous, local Ca2+ release events or Ca2+ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca2+-binding protein that associates with cardiac RyRs and quickly stops Ca2+ release in the heart, provides a potential mechanism to modulate Ca2+ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca2+ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca2+-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca2+ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca2+ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca2+ spark properties. Perfusion of 2 μm sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca2+ sparks, demonstrating that sorcin effectively regulates Ca2+ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle. PMID:16931553

  19. Roles of prostaglandin E2 in the cochlea.

    PubMed

    Nakagawa, Takayuki

    2011-06-01

    Prostaglandins are one of the major groups of chemical mediators in the mammalian body. Among prostaglandins, prostaglandin E2 (PGE2) is the most abundant prostanoid in humans and involved in regulating many different fundamental biological functions. PGE2 signaling is mediated by four distinct E-prostanoid receptors (EPs) namely EP1-4. Recently, accumulating evidence indicates critical, but complex roles of EP signaling in the pathogenesis of neuronal diseases depending on the context of neuronal injury. Four distinct EPs are expressed in the stria vascularis, spiral ligament, spiral ganglion and organ of Corti, indicating an involvement of EP signaling in the cochlear function. Activation of EP4 in cochleae significantly attenuates noise-induced damage in cochleae, and activation of EP2 or EP4 induces the formation of vascular endothelial growth factor in cochleae. These findings strongly suggest that individual EP signaling may be involved in the maintenance of the cochlear sensory system similarly to the central nervous system. This review highlights recent findings on EP signaling in the central nervous system, and presents its possible roles in regulation of blood flow, protection of sensory cells and immune responses in cochleae. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Insights into Cullin-RING E3 ubiquitin ligase recruitment: structure of the VHL-EloBC-Cul2 complex.

    PubMed

    Nguyen, Henry C; Yang, Haitao; Fribourgh, Jennifer L; Wolfe, Leslie S; Xiong, Yong

    2015-03-03

    The von Hippel-Lindau tumor suppressor protein (VHL) recruits a Cullin 2 (Cul2) E3 ubiquitin ligase to downregulate HIF-1α, an essential transcription factor for the hypoxia response. Mutations in VHL lead to VHL disease and renal cell carcinomas. Inhibition of this pathway to upregulate erythropoietin production is a promising new therapy to treat ischemia and chronic anemia. Here, we report the crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C (EloC). Cul2 interacts with both the VHL BC box and cullin box and a novel EloC site. Comparison with other cullin E3 ligase structures shows that there is a conserved, yet flexible, cullin recognition module and that cullin selectivity is influenced by distinct electrostatic interactions. Our structure provides a structural basis for the study of the pathogenesis of VHL disease and rationale for the design of novel compounds that may modulate cullin-substrate receptor interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Direct Observations of ULF and Whistler-Mode Chorus Modulation of 500eV EDI Electrons by MMS

    NASA Astrophysics Data System (ADS)

    Paulson, K. W.; Argall, M. R.; Ahmadi, N.; Torbert, R. B.; Le Contel, O.; Ergun, R.; Khotyaintsev, Y. V.; Strangeway, R. J.; Magnes, W.; Russell, C. T.

    2016-12-01

    We present here direct observations of chorus-wave modulated field-aligned 500 eV electrons using the Electron Drift Instrument (EDI) on board the Magnetospheric Multiscale mission. These periods of wave activity were additionally observed to be modulated by Pc5-frequency magnetic perturbations, some of which have been identified as drifting mirror-mode structures. The spacecraft encountered these mirror-mode structures just inside of the duskside magnetopause. Using the high sampling rate provided by EDI in burst sampling mode, we are able to observe the individual count fluctuations of field-aligned electrons in this region up to 512 Hz. We use the multiple look directions of EDI to generate both pitch angle and gyrophase plots of the fluctuating counts. Our observations often show unidirectional flow of these modulated electrons along the background field, and in some cases demonstrate gyrophase bunching in the wave region.

  2. Hybrid metasurface for ultra-broadband terahertz modulation

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

    Heyes, Jane E.; Withayachumnankul, Withawat; Grady, Nathaniel K.

    2014-11-05

    We demonstrate an ultra-broadband free-space terahertz modulator based on a semiconductor-integrated metasurface. The modulator is made of a planar array of metal cut-wires on a silicon-on-sapphire substrate, where the silicon layer functions as photoconductive switches. Without external excitation, the cut-wire array exhibits a Lorentzian resonant response with a transmission passband spanning dc up to the fundamental dipole resonance above 2 THz. Under photoexcitation with 1.55 eV near-infrared light, the silicon regions in the cut-wire gaps become highly conductive, causing a transition of the resonant metasurface to a wire grating with a Drude response. In effect, the low-frequency passband below 2more » THz evolves into a stopband for the incident terahertz waves. Experimental validations confirm a bandwidth of at least 100%, spanning 0.5 to 1.5 THz with -10 dB modulation depth. This modulation depth is far superior to -5 dB achievable from a plain silicon-on-sapphire substrate with effectively 25 times higher pumping energy. The proposed concept of ultra-broadband metasurface modulator can be readily extended to electrically controlled terahertz wave modulation.« less

  3. Quantum criticality and nodal superconductivity in the FeAs-based superconductor KFe2As2.

    PubMed

    Dong, J K; Zhou, S Y; Guan, T Y; Zhang, H; Dai, Y F; Qiu, X; Wang, X F; He, Y; Chen, X H; Li, S Y

    2010-02-26

    The in-plane resistivity rho and thermal conductivity kappa of the FeAs-based superconductor KFe2As2 single crystal were measured down to 50 mK. We observe non-Fermi-liquid behavior rho(T) approximately T{1.5} at H{c{2}}=5 T, and the development of a Fermi liquid state with rho(T) approximately T{2} when further increasing the field. This suggests a field-induced quantum critical point, occurring at the superconducting upper critical field H{c{2}}. In zero field, there is a large residual linear term kappa{0}/T, and the field dependence of kappa_{0}/T mimics that in d-wave cuprate superconductors. This indicates that the superconducting gaps in KFe2As2 have nodes, likely d-wave symmetry. Such a nodal superconductivity is attributed to the antiferromagnetic spin fluctuations near the quantum critical point.

  4. Ferromagnetic quantum critical point in CePd2P2 with Pd → Ni substitution

    NASA Astrophysics Data System (ADS)

    Lai, Y.; Bone, S. E.; Minasian, S.; Ferrier, M. G.; Lezama-Pacheco, J.; Mocko, V.; Ditter, A. S.; Kozimor, S. A.; Seidler, G. T.; Nelson, W. L.; Chiu, Y.-C.; Huang, K.; Potter, W.; Graf, D.; Albrecht-Schmitt, T. E.; Baumbach, R. E.

    2018-06-01

    An investigation of the structural, thermodynamic, and electronic transport properties of the isoelectronic chemical substitution series Ce (Pd1-xNix) 2P2 is reported, where a possible ferromagnetic quantum critical point is uncovered in the temperature-concentration (T -x ) phase diagram. This behavior results from the simultaneous contraction of the unit cell volume, which tunes the relative strengths of the Kondo and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions, and the introduction of disorder through alloying. Near the critical region at xcr≈ 0.7, the rate of contraction of the unit cell volume strengthens, indicating that the cerium f valence crosses over from trivalent to a noninteger value. Consistent with this picture, x-ray absorption spectroscopy measurements reveal that while CePd2P2 has a purely trivalent cerium f state, CeNi2P2 has a small (<10 %) tetravalent contribution. In a broad region around xcr, there is a breakdown of Fermi-liquid temperature dependences, signaling the influence of quantum critical fluctuations and disorder effects. Measurements of clean CePd2P2 furthermore show that applied pressure has an initial effect similar to alloying on the ferromagnetic order. From these results, CePd2P2 emerges as a keystone system to test theories such as the Belitz-Kirkpatrick-Vojta model for ferromagnetic quantum criticality, where distinct behaviors are expected in the dirty and clean limits.

  5. STS-55 German Payload Specialist Walter freefloats inside the SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter demonstrates the microgravity aboard the Spacelab Deutsche 2 (SL-D2) science module in Columbia's, Orbiter Vehicle (OV) 102's, payload bay (PLB). The module served as his space laboratory and that of his six crewmates for 10 days. Walter represents the German Aerospace Research Establishment (DLR).

  6. Participative Critical Enquiry in Graduate Field-Based Learning

    ERIC Educational Resources Information Center

    Reilly, Kathy; Clavin, Alma; Morrissey, John

    2016-01-01

    This paper outlines a critical pedagogic approach to field-based learning (FBL) at graduate level. Drawing on student experience stemming from a FBL module and as part of an MA programme in Environment, Society and Development, the paper addresses the complexities associated with student-led, participative critical enquiry during fieldwork in…

  7. Low temperature anomalous field effect in SrxBa1-xNb2O6 uniaxial relaxor ferroelectric seen via acoustic emission

    NASA Astrophysics Data System (ADS)

    Dul'kin, E.; Kojima, S.; Roth, M.

    2012-04-01

    Sr0.75Ba0.25Nb2O6 [100]-oriented uniaxial tungsten bronze relaxor crystals have been studied by means of dedicated acoustic emission during their thermal cycling in 150-300 K temperature range under dc electric field (E). A 1st order transition in a modulated incommensurate tetragonal phase has been successfully detected at Tmi = 198 K on heating and Tmi = 184 K on cooling, respectively. As field E enhances, a thermal hysteresis gradually narrows and vanishes in the critical point at Eth = 0.31 kV/cm, above which a phase transition becomes to 2nd order. The Tmi(E) dependence looks as a V-shape dip, not similar that previously has been looked as a smeared minimum between both the two polar and nonpolar tetragonal phases near Tm = 220 ÷ 230 K in the same crystals (Dul'kin et al., J Appl. Phys. 110, 044106 (2011)). Due to such a V-shape dip is characteristic for Pb-based multiaxial perovskite relaxor, a rhombohedral phase is waited to be induced by a field E in the critical point temperature range. The emergence of this rhombohedral phase as a crucial evidence of an orthorhombic phase presumably existing within the modulated incommensurate tetragonal phase in tungsten bronze SrxBa1-xNb2O6 relaxor is discussed.

  8. Nonlinear modulation near the Lighthill instability threshold in 2+1 Whitham theory

    NASA Astrophysics Data System (ADS)

    Bridges, Thomas J.; Ratliff, Daniel J.

    2018-04-01

    The dispersionless Whitham modulation equations in 2+1 (two space dimensions and time) are reviewed and the instabilities identified. The modulation theory is then reformulated, near the Lighthill instability threshold, with a slow phase, moving frame and different scalings. The resulting nonlinear phase modulation equation near the Lighthill surfaces is a geometric form of the 2+1 two-way Boussinesq equation. This equation is universal in the same sense as Whitham theory. Moreover, it is dispersive, and it has a wide range of interesting multi-periodic, quasi-periodic and multi-pulse localized solutions. For illustration the theory is applied to a complex nonlinear 2+1 Klein-Gordon equation which has two Lighthill surfaces in the manifold of periodic travelling waves. This article is part of the theme issue `Stability of nonlinear waves and patterns and related topics'.

  9. E-cadherin Is Critical for Collective Sheet Migration and Is Regulated by the Chemokine CXCL12 Protein During Restitution*

    PubMed Central

    Hwang, Soonyean; Zimmerman, Noah P.; Agle, Kimberle A.; Turner, Jerrold R.; Kumar, Suresh N.; Dwinell, Michael B.

    2012-01-01

    Chemokines and other immune mediators enhance epithelial barrier repair. The intestinal barrier is established by highly regulated cell-cell contacts between epithelial cells. The goal of these studies was to define the role for the chemokine CXCL12 in regulating E-cadherin during collective sheet migration during epithelial restitution. Mechanisms regulating E-cadherin were investigated using Caco2BBE and IEC-6 model epithelia. Genetic knockdown confirmed a critical role for E-cadherin in in vitro restitution and in vivo wound repair. During restitution, both CXCL12 and TGF-β1 tightened the monolayer by decreasing the paracellular space between migrating epithelial cells. However, CXCL12 differed from TGF-β1 by stimulating the significant increase in E-cadherin membrane localization during restitution. Chemokine-stimulated relocalization of E-cadherin was paralleled by an increase in barrier integrity of polarized epithelium during restitution. CXCL12 activation of its cognate receptor CXCR4 stimulated E-cadherin localization and monolayer tightening through Rho-associated protein kinase activation and F-actin reorganization. These data demonstrate a key role for E-cadherin in intestinal epithelial restitution. PMID:22549778

  10. Addendum to the User Manual for NASGRO Elastic-Plastic Fracture Mechanics Software Module

    NASA Technical Reports Server (NTRS)

    Gregg, M. Wayne (Technical Monitor); Chell, Graham; Gardner, Brian

    2003-01-01

    The elastic-plastic fracture mechanics modules in NASGRO have been enhanced by the addition of of the following: new J-integral solutions based on the reference stress method and finite element solutions; the extension of the critical crack and critical load modules for cracks with two degrees of freedom that tear and failure by ductile instability; the addition of a proof test analysis module that includes safe life analysis, calculates proof loads, and determines the flaw screening 1 capability for a given proof load; the addition of a tear-fatigue module for ductile materials that simultaneously tear and extend by fatigue; and a multiple cycle proof test module for estimating service reliability following a proof test.

  11. Heat-Storage Modules Containing LiNO3-3H2O and Graphite Foam

    NASA Technical Reports Server (NTRS)

    Bootle, John

    2008-01-01

    A heat-storage module based on a commercial open-cell graphite foam (Poco-Foam or equivalent) imbued with lithium nitrate trihydrate (LiNO3-3H2O) has been developed as a prototype of other such modules for use as short-term heat sources or heat sinks in the temperature range of approximately 28 to 30 C. In this module, the LiNO3-3H2O serves as a phase-change heat-storage material and the graphite foam as thermally conductive filler for transferring heat to or from the phase-change material. In comparison with typical prior heat-storage modules in which paraffins are the phase-change materials and aluminum fins are the thermally conductive fillers, this module has more than twice the heat-storage capacity per unit volume.

  12. GHz Modulation of GaAs-Based Bipolar Cascade VCSELs (Preprint)

    DTIC Science & Technology

    2006-11-01

    VCSELs were grown on n+ GaAs substrates by molecular beam epitaxy . The laser cavities consist of 1-, 2-, or 3-stage 52λ microcavi- ties, each containing...AFRL-SN-WP-TP-2006-128 GHz MODULATION OF GaAs-BASED BIPOLAR CASCADE VCSELs (PREPRINT) W.J. Siskaninetz, R.G. Bedford, T.R. Nelson, Jr., J.E...TITLE AND SUBTITLE GHz MODULATION OF GaAs-BASED BIPOLAR CASCADE VCSELs (PREPRINT) 5c. PROGRAM ELEMENT NUMBER 69199F 5d. PROJECT NUMBER 2002 5e

  13. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development.

    PubMed

    Cerqueira, Débora M; Bodnar, Andrew J; Phua, Yu Leng; Freer, Rachel; Hemker, Shelby L; Walensky, Loren D; Hukriede, Neil A; Ho, Jacqueline

    2017-08-01

    Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in an earlier study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer from nephron progenitors results in premature depletion of the progenitors and increased expression of the proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model with conditional deletion of both Dicer and Bim , to determine the biologic significance of increased Bim expression in Dicer -deficient nephron progenitors. The loss of Bim partially restored the number of nephron progenitors and improved nephron formation. The number of progenitors undergoing apoptosis was significantly reduced in kidneys with loss of a single allele, or both alleles, of Bim compared to mutant kidneys. Furthermore, 2 miRNAs expressed in nephron progenitors ( miR-17 and miR-106b) regulated Bim levels in vitro and in vivo Together, these data suggest that miRNA-mediated regulation of Bim controls nephron progenitor survival during nephrogenesis, as one potential means of regulating nephron endowment.-Cerqueira, D. M., Bodnar, A. J., Phua, Y. L., Freer, R., Hemker, S. L., Walensky, L. D., Hukriede, N. A., Ho, J. Bim gene dosage is critical in modulating nephron progenitor survival in the absence of microRNAs during kidney development. © FASEB.

  14. Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid leukemia (AML) and the effect of pharmacological inhibition of Nrf2.

    PubMed

    Karathedath, Sreeja; Rajamani, Bharathi M; Musheer Aalam, Syed Mohammed; Abraham, Ajay; Varatharajan, Savitha; Krishnamurthy, Partha; Mathews, Vikram; Velayudhan, Shaji Ramachandran; Balasubramanian, Poonkuzhali

    2017-01-01

    Cytarabine (Ara-C) and Daunorubicin (Dnr) forms the backbone of acute myeloid leukemia (AML) therapy. Drug resistance and toxic side effects pose a major threat to treatment success and hence alternate less toxic therapies are warranted. NF-E2 related factor-2 (Nrf2), a master regulator of antioxidant response is implicated in chemoresistance in solid tumors. However, little is known about the role of Nrf2 in AML chemoresistance and the effect of pharmacological inhibitor brusatol in modulating this resistance. Primary AML samples with high ex-vivo IC50 to Ara-C, ATO, Dnr had significantly high NRF2 RNA expression. Gene-specific knockdown of NRF2 improved sensitivity to these drugs in resistant AML cell lines by decreasing the expression of downstream antioxidant targets of Nrf2 by compromising the cell's ability to scavenge the ROS. Treatment with brusatol, a pharmacological inhibitor of Nrf2, improved sensitivity to Ara-C, ATO, and Dnr and reduced colony formation capacity. AML cell lines stably overexpressing NRF2 showed increased resistance to ATO, Dnr and Ara-C and increased expression of downstream targets. This study demonstrates that Nrf2 could be an ideal druggable target in AML, more so to the drugs that function through ROS, suggesting the possibility of using Nrf2 inhibitors in combination with chemotherapeutic agents to modulate drug resistance in AML.

  15. The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors.

    PubMed

    Kim, Jieun; Lee, Haeryung; Kim, Yujin; Yoo, Sooyeon; Park, Eunjeong; Park, Soochul

    2010-04-01

    We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

  16. CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes

    PubMed Central

    Singh, Randeep K.; Dagnino, Lina

    2017-01-01

    The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation. PMID:27903963

  17. CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

    PubMed

    Singh, Randeep K; Dagnino, Lina

    2017-01-17

    The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

  18. Using Modules with MPICH-G2 (and "Loose Ends")

    NASA Technical Reports Server (NTRS)

    Chang, Johnny; Thigpen, William W. (Technical Monitor)

    2002-01-01

    A new approach to running complex, distributed MPI jobs using the MPICH-G2 library is described. This approach allows the user to switch between different versions of compilers, system libraries, MPI libraries, etc. via the "module" command. The key idea is a departure from the prescribed "(jobtype=mpi)" approach to running distributed MPI jobs. The new method requires the user to provide a script that will be run as the "executable" with the "(jobtype=single)" RSL attribute. The major advantage of the proposed method is to enable users to decide in their own script what modules, environment, etc. they would like to have in running their job.

  19. Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels.

    PubMed

    Wilkinson, W J; Gadeberg, H C; Harrison, A W J; Allen, N D; Riccardi, D; Kemp, P J

    2009-10-01

    Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated. Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X(2), P2X(3), P2X(2/3) and P2X(4) receptors and in rat pheochromocytoma (PC12) cells known to express native P2X(2) receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2). CO was a potent and selective modulator of native P2X(2) receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3',5'-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X(2) currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X(2/3) and P2X(4) receptors, but was without effect on P2X(3) receptors. These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X(2) receptors in physiological systems.

  20. SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells

    PubMed Central

    Myers, Samuel A; Peddada, Sailaja; Chatterjee, Nilanjana; Friedrich, Tara; Tomoda, Kiichrio; Krings, Gregor; Thomas, Sean; Maynard, Jason; Broeker, Michael; Thomson, Matthew; Pollard, Katherine; Yamanaka, Shinya; Burlingame, Alma L; Panning, Barbara

    2016-01-01

    The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. DOI: http://dx.doi.org/10.7554/eLife.10647.001 PMID:26949256

  1. Optical modulation techniques for analog signal processing and CMOS compatible electro-optic modulation

    NASA Astrophysics Data System (ADS)

    Gill, Douglas M.; Rasras, Mahmoud; Tu, Kun-Yii; Chen, Young-Kai; White, Alice E.; Patel, Sanjay S.; Carothers, Daniel; Pomerene, Andrew; Kamocsai, Robert; Beattie, James; Kopa, Anthony; Apsel, Alyssa; Beals, Mark; Mitchel, Jurgen; Liu, Jifeng; Kimerling, Lionel C.

    2008-02-01

    Integrating electronic and photonic functions onto a single silicon-based chip using techniques compatible with mass-production CMOS electronics will enable new design paradigms for existing system architectures and open new opportunities for electro-optic applications with the potential to dramatically change the management, cost, footprint, weight, and power consumption of today's communication systems. While broadband analog system applications represent a smaller volume market than that for digital data transmission, there are significant deployments of analog electro-optic systems for commercial and military applications. Broadband linear modulation is a critical building block in optical analog signal processing and also could have significant applications in digital communication systems. Recently, broadband electro-optic modulators on a silicon platform have been demonstrated based on the plasma dispersion effect. The use of the plasma dispersion effect within a CMOS compatible waveguide creates new challenges and opportunities for analog signal processing since the index and propagation loss change within the waveguide during modulation. We will review the current status of silicon-based electrooptic modulators and also linearization techniques for optical modulation.

  2. Personalising e-learning modules: targeting Rasmussen levels using XML.

    PubMed

    Renard, J M; Leroy, S; Camus, H; Picavet, M; Beuscart, R

    2003-01-01

    The development of Internet technologies has made it possible to increase the number and the diversity of on-line resources for teachers and students. Initiatives like the French-speaking Virtual Medical University Project (UMVF) try to organise the access to these resources. But both teachers and students are working on a partly redundant subset of knowledge. From the analysis of some French courses we propose a model for knowledge organisation derived from Rasmussen's stepladder. In the context of decision-making Rasmussen has identified skill-based, rule-based and knowledge-based levels for the mental process. In the medical context of problem-solving, we apply these three levels to the definition of three students levels: beginners, intermediate-level learners, experts. Based on our model, we build a representation of the hierarchical structure of data using XML language. We use XSLT Transformation Language in order to filter relevant data according to student level and to propose an appropriate display on students' terminal. The model and the XML implementation we define help to design tools for building personalised e-learning modules.

  3. Philosophy: A Key To Open the Door to Critical Thinking.

    ERIC Educational Resources Information Center

    Clarke, David J.; Holt, Janet

    2001-01-01

    A learning module for nursing attempts to prepare nurses to understand philosophical inquiry and develop critical thinking skills. Teaching strategies used included exercises involving verbal disagreement and ambiguity and critical examination of publications. (Contains 42 references.) (SK)

  4. Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes.

    PubMed

    Tiano, Joseph; Mauvais-Jarvis, Franck

    2012-01-01

    We recently showed that the female hormone 17β-estradiol (E2) protects against β-cell failure in rodent models of type 2 diabetes (T2D) by suppressing islet fatty acids and glycerolipids synthesis, thus preventing lipotoxic β-cell failure. E2 anti-lipogenic actions were recapitulated by pharmacological activation of the estrogen receptor (ER)α, ERβ and the G-protein coupled ER (GPER) in cultured rodent and human β-cells. In vivo, in mouse islets, ERα activation inhibited β-cell lipogenesis by suppressing fatty acid synthase expression (and activity) via an extranuclear, estrogen response element (ERE)-independent pathway requiring the signal transducer and activator of transcription 3. Here, we show that in INS-1 insulin-secreting cells, the selective ER modulator (SERM), Raloxifene, behaves both as ER antagonist with regard to nuclear ERE-dependent actions and as an ER agonist with regard to suppressing triglyceride accumulation. This additional finding opens the perspective that SERMs harboring ER agonistic activity in β-cells could have application in postmenopausal prevention of T2D. Additional studies using novel generation SERMs are needed to address this issue.

  5. Phosphorylation of eIF2α via the general control kinase, GCN2, modulates the ability of renal medullary cells to survive high urea stress

    PubMed Central

    Cai, Qi

    2011-01-01

    The phosphorylation of the α-subunit of the eukaryotic translation initiation factor 2 (eIF2α) occurs under many stress conditions in mammalian cells and is mediated by one of four eIF2α kinases: PERK, PKR, GCN2, and HRI. Cells of the renal medulla are regularly exposed to fluctuating concentrations of urea and sodium, the extracellular solutes responsible for the high osmolality in the renal medulla, and thus the kidneys ability to concentrate the urine in times of dehydration. Urea stress is known to initiate molecular responses that diverge from those seen in response to hypertonic stress (NaCl). We show that urea-inducible GCN2 activation initiates the phosphorylation of eIF2α and the downstream increase of activating transcription factor 3 (ATF3). Loss of GCN2 sensitized cells to urea stress, increasing the expression of activated caspase-3 and decreasing cell survival. Loss of GCN2 ablated urea-induced phosphorylation of eIF2α and reduced the expression of ATF3. PMID:21880833

  6. STS-42 MS/PLC Norman E. Thagard adjusts Rack 10 FES equipment in IML-1 module

    NASA Image and Video Library

    1992-01-30

    STS042-05-006 (22-30 Jan 1992) --- Astronaut Norman E. Thagard, payload commander, performs the Fluids Experiment System (FES) in the International Microgravity Laboratory (IML-1) science module. The FES is a NASA-developed facility that produces optical images of fluid flows during the processing of materials in space. The system's sophisticated optics consist of a laser to make holograms of samples and a video camera to record images of flows in and around samples. Thagard was joined by six fellow crewmembers for eight days of scientific research aboard Discovery in Earth-orbit. Most of their on-duty time was spent in this IML-1 science module, positioned in the cargo bay and attached via a tunnel to Discovery's airlock.

  7. Features of anti-inflammatory effects of modulated extremely high-frequency electromagnetic radiation.

    PubMed

    Gapeyev, Andrew B; Mikhailik, Elena N; Chemeris, Nikolay K

    2009-09-01

    Using a model of acute zymosan-induced paw edema in NMRI mice, we test the hypothesis that anti-inflammatory effects of extremely high-frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1-0.7 mW/cm(2) and frequencies from the range of 42.2-42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti-inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03-100 Hz did not lead to considerable changes in the effect level. On the contrary, at "ineffective" carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07-0.1 and 20-30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti-inflammatory action of low-intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed.

  8. Modulation of Nrf2 by Olive Oil and Wine Polyphenols and Neuroprotection

    PubMed Central

    Martínez-Huélamo, Miriam; Boronat, Anna; de la Torre, Rafael

    2017-01-01

    Strong adherence to a Mediterranean diet is associated with improved cognitive function and a lower prevalence of mild cognitive impairment. Olive oil and red wine are rich sources of polyphenols which are responsible in part for the beneficial effects on cognitive functioning. Polyphenols induce endogenous antioxidant defense mechanisms by modulating transcription factors such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This review discusses the scientific data supporting the modulating effect of olive oil and red wine polyphenols on Nrf2 expression, and the potential health benefits associated with cognitive functioning. PMID:28954417

  9. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-2, Pump Functional Testing.

    ERIC Educational Resources Information Center

    Wasel, Ed; Espy, John

    This second in a series of eight modules for a course titled Mechanical Inspection describes typical pump functional tests which are performed after pump installation and prior to release of the plant for unrestricted power operation. The module follows a typical format that includes the following sections: (1) introduction, (2) module…

  10. Flux-periodicity crossover from h/2e to h/e in aluminium nano-loops

    NASA Astrophysics Data System (ADS)

    Espy, C.; Sharon, O. J.; Braun, J.; Garreis, R.; Strigl, F.; Shaulov, A.; Leiderer, P.; Scheer, E.; Yeshurun, Y.

    2018-03-01

    We study the magnetoresistance of aluminium ‘double-networks’ formed by connecting the vertexes of nano-loops with relatively long wires, creating two interlaced subnetworks of small and large loops (SL and LL, respectively). Far below the critical temperature, Aharonov-Bohm like quantum interference effects are observed for both the LL and the SL subnetworks. When approaching T c, both exhibit the usual Little-Parks oscillations, with periodicity of the superconducting flux quantum Φ 0 =h/2e. For one sample, with a relatively large coherence length, ξ, at temperatures very close to T c, the Φ 0 periodicity of the SL disappears, and the waveform of the first period is consistent with that predicted recently for loops with a size a < ξ, indicating a crossover to 2Φ 0 periodicity.

  11. GSK3β regulates AKT-induced central nervous system axon regeneration via an eIF2Bε-dependent, mTORC1-independent pathway.

    PubMed

    Guo, Xinzheng; Snider, William D; Chen, Bo

    2016-03-14

    Axons fail to regenerate after central nervous system (CNS) injury. Modulation of the PTEN/mTORC1 pathway in retinal ganglion cells (RGCs) promotes axon regeneration after optic nerve injury. Here, we report that AKT activation, downstream of Pten deletion, promotes axon regeneration and RGC survival. We further demonstrate that GSK3β plays an indispensable role in mediating AKT-induced axon regeneration. Deletion or inactivation of GSK3β promotes axon regeneration independently of the mTORC1 pathway, whereas constitutive activation of GSK3β reduces AKT-induced axon regeneration. Importantly, we have identified eIF2Bε as a novel downstream effector of GSK3β in regulating axon regeneration. Inactivation of eIF2Bε reduces both GSK3β and AKT-mediated effects on axon regeneration. Constitutive activation of eIF2Bε is sufficient to promote axon regeneration. Our results reveal a key role of the AKT-GSK3β-eIF2Bε signaling module in regulating axon regeneration in the adult mammalian CNS.

  12. Paradoxical effects of 137Cs irradiation on pharmacological stimulation of reactive oxygen species in hippocampal slices from apoE2 and apoE4 mice.

    PubMed

    Villasana, Laura E; Akinyeke, Tunde; Weber, Sydney; Raber, Jacob

    2017-09-29

    In humans, apoE, which plays a role in repair, is expressed in three isoforms: E2, E3, and E4. E4 is a risk factor for age-related cognitive decline (ACD) and Alzheimer's disease (AD), particularly in women. In contrast, E2 is a protective factor for ACD and AD. E2 and E4 might also differ in their response to cranial 137 Cs irradiation, a form of radiation typically used in a clinical setting for the treatment of cancer. This might be mediated by reactive oxygen species (ROS) in an-apoE isoform-dependent fashion. E2 and E4 female mice received sham-irradiation or cranial irradiation at 8 weeks of age and a standard mouse chow or a diet supplemented with the antioxidant alpha-lipoic acid (ALA) starting at 6 weeks of age. Behavioral and cognitive performance of the mice were assessed 12 weeks later. Subsequently, the generation of ROS in hippocampal slices was analyzed. Compared to sham-irradiated E4 mice, irradiated E4 mice showed enhanced spatial memory in the water maze. This was associated with increased hippocampal PMA-induction of ROS. Similar effects were not seen in E2 mice. Irradiation increased endogenous hippocampal ROS levels in E2 mice while decreasing those in E4 mice. NADPH activity and MnSOD levels were higher in sham-irradiated E2 than E4 mice. Irradiation increased NADPH activity and MnSOD levels in hemi brains of E4 mice but not in those of E2 mice. ALA did not affect behavioral and cognitive performance or hippocampal formation of ROS in either genotype. Thus, apoE isoforms modulate the radiation response.

  13. Soluble Iron in Alveolar Macrophages Modulates Iron Oxide Particle-Induced Inflammatory Response via Prostaglandin E2 Synthesis

    EPA Science Inventory

    Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of inflammation by PM-associated soluble metal, we investigated intracellular solubility of radiolabelled iron oxide (59

  14. Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

    PubMed Central

    2014-01-01

    Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure–activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators. PMID:24905252

  15. Provide for Student Safety. Second Edition. Module E-5 of Category E--Instructional Management. Professional Teacher Education Module Series

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    One in a series of 127 performance-based teacher education learning packages focusing on specific professional competencies of vocational teachers, this learning module deals with providing for student safety. It consists of four learning experiences. Covered in the individual learning experiences are the following topics: providing for student…

  16. E2 superfamily of ubiquitin-conjugating enzymes: constitutively active or activated through phosphorylation in the catalytic cleft.

    PubMed

    Valimberti, Ilaria; Tiberti, Matteo; Lambrughi, Matteo; Sarcevic, Boris; Papaleo, Elena

    2015-10-14

    Protein phosphorylation is a modification that offers a dynamic and reversible mechanism to regulate the majority of cellular processes. Numerous diseases are associated with aberrant regulation of phosphorylation-induced switches. Phosphorylation is emerging as a mechanism to modulate ubiquitination by regulating key enzymes in this pathway. The molecular mechanisms underpinning how phosphorylation regulates ubiquitinating enzymes, however, are elusive. Here, we show the high conservation of a functional site in E2 ubiquitin-conjugating enzymes. In catalytically active E2s, this site contains aspartate or a phosphorylatable serine and we refer to it as the conserved E2 serine/aspartate (CES/D) site. Molecular simulations of substrate-bound and -unbound forms of wild type, mutant and phosphorylated E2s, provide atomistic insight into the role of the CES/D residue for optimal E2 activity. Both the size and charge of the side group at the site play a central role in aligning the substrate lysine toward E2 catalytic cysteine to control ubiquitination efficiency. The CES/D site contributes to the fingerprint of the E2 superfamily. We propose that E2 enzymes can be divided into constitutively active or regulated families. E2s characterized by an aspartate at the CES/D site signify constitutively active E2s, whereas those containing a serine can be regulated by phosphorylation.

  17. H2O2 modulates the energetic metabolism of the cloud microbiome

    NASA Astrophysics Data System (ADS)

    Wirgot, Nolwenn; Vinatier, Virginie; Deguillaume, Laurent; Sancelme, Martine; Delort, Anne-Marie

    2017-12-01

    Chemical reactions in clouds lead to oxidation processes driven by radicals (mainly HO⚫, NO3⚫, or HO2⚫) or strong oxidants such as H2O2, O3, nitrate, and nitrite. Among those species, hydrogen peroxide plays a central role in the cloud chemistry by driving its oxidant capacity. In cloud droplets, H2O2 is transformed by microorganisms which are metabolically active. Biological activity can therefore impact the cloud oxidant capacity. The present article aims at highlighting the interactions between H2O2 and microorganisms within the cloud system. First, experiments were performed with selected strains studied as a reference isolated from clouds in microcosms designed to mimic the cloud chemical composition, including the presence of light and iron. Biotic and abiotic degradation rates of H2O2 were measured and results showed that biodegradation was the most efficient process together with the photo-Fenton process. H2O2 strongly impacted the microbial energetic state as shown by adenosine triphosphate (ATP) measurements in the presence and absence of H2O2. This ATP depletion was not due to the loss of cell viability. Secondly, correlation studies were performed based on real cloud measurements from 37 cloud samples collected at the PUY station (1465 m a.s.l., France). The results support a strong correlation between ATP and H2O2 concentrations and confirm that H2O2 modulates the energetic metabolism of the cloud microbiome. The modulation of microbial metabolism by H2O2 concentration could thus impact cloud chemistry, in particular the biotransformation rates of carbon compounds, and consequently can perturb the way the cloud system is modifying the global atmospheric chemistry.

  18. SU-E-T-317: Dynamic Modulated Brachytherapy (DMBT): Robotic Applicator Design.

    PubMed

    Han, Dae Yup; Webster, Matthew J; Devic, Slobodan; Vuong, Te; Scanderbeg, Dan; Song, William Y

    2012-06-01

    To investigate the hardware necessary for implementing our Dynamic Modulated Brachytherapy (DMBT) treatment concept for rectal cancer. The DMBT robot has three major parts: 1) shield and shield delivery module, 2) controlling module, and 3) DMBT controlling and monitoring software. The shield is a tungsten alloy cylinder (r=0.95cm, l=4.5cm) with a 5.5mm rectangular-shaped opening. The shield is controlled by an aluminum pipe with gear set (1:3) and linear actuator (2mm/turn). An Ir-192 radiation source will be placed through the aluminum pipe. The power source is a Nema-17 stepping motor with EvoDrive ST-17 (EVA Robotics, Queensland, Australia) and USB-6009 DAQ (National Instrument, Austin, TX). With our in-house operating program through LabView (National Instrument, Austin, TX), we can make and load plans for treatment as well as testing. Checking the shield position is also possible through the operating program. For safety, a lexan sheath tube and emergency buttons are built-in. The DMBT robot has 2 degrees of freedom, which are linear translation and rotation. With our power delivery system, the spatial resolutions are 0.0125mm (linear stage) and 0.012Ëš (rotation). In 0.5s, motors achieve the desired position with the maximum speeds 450 step/s (1Ëš), 7,500 step/s (30Ëš), and 12,000 step/s (5mm). Four registers are triggered with USB-6009 DAQ signals. The operating program includes gages for checking shield position, loading treatment plans, and safety buttons. In all, we have designed the hardware components of the DMBT system for rectal cancer. For treatment, the system needs more elements to support the DMBT robot; lexan sheath tube holder, DMBT robot security joint, and a system for reducing friction between the tube and shield. We will also refine our system to be more compact by using DC servomotors instead of the larger Nema-17 stepping motors. © 2012 American Association of Physicists in Medicine.

  19. A hybrid electro-optic polymer and TiO2 double-slot waveguide modulator

    PubMed Central

    Qiu, Feng; Spring, Andrew M.; Maeda, Daisuke; Ozawa, Masa-aki; Odoi, Keisuke; Otomo, Akira; Aoki, Isao; Yokoyama, Shiyoshi

    2015-01-01

    An electro-optic (EO) modulator using a TiO2 slot hybrid waveguide has been designed and fabricated. Optical mode calculations revealed that the mode was primarily confined within the slots when using a double-slot configuration, thus achieving a high EO activity experimentally. The TiO2 slots also acted as an important barrier to induce an enhanced DC field during the poling of the EO polymer and the driving of the EO modulator. The hybrid phase modulator exhibited a driving voltage (Vπ) of 1.6 V at 1550 nm, which can be further reduced to 0.8 V in a 1 cm-long push-pull Mach–Zehnder interferometer (MZI) structure. The modulator demonstrated a low propagation loss of 5 dB/cm and a relatively high end-fire coupling efficiency. PMID:25708425

  20. Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

    PubMed Central

    Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

    2014-01-01

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731