Clinically speaking: A communication skills program for students from non-English speaking backgrounds.

PubMed

Miguel, Caroline San; Rogan, Fran; Kilstoff, Kathleen; Brown, Di

2006-09-01

This paper reports on the design, delivery and evaluation of an innovative oral communication skills program for first year students in a Bachelor of Nursing degree at an Australian university. This program was introduced in 2004 to meet the needs of first year undergraduate students from non-English speaking backgrounds who had experienced difficulties with spoken English while on clinical placement. The program consisted of early identification of students in need of communication development, a series of classes incorporated into the degree program to address students' needs, followed by a clinical placement block. This paper describes the structure of the program, discusses some of the major problems encountered by students in the clinical setting and presents some of the teaching strategies used to address these problems. Evaluations of the program suggest that students' communication skills and confidence improved, resulting in a more positive clinical experience for the majority of students.

Navy DDG-51 and DDG-1000 Destroyer Programs: Background and Issues for Congress

DTIC Science & Technology

2015-12-17

Navy DDG- 51 and DDG-1000 Destroyer Programs: Background and Issues for Congress Ronald O’Rourke Specialist in Naval Affairs December 17......Congressional Research Service Summary The Navy has been procuring Arleigh Burke (DDG- 51 ) class Aegis destroyers since FY1985. The two DDG- 51 class

An Adapted Dialogic Reading Program for Turkish Kindergarteners from Low Socio-Economic Backgrounds

ERIC Educational Resources Information Center

Ergül, Cevriye; Akoglu, Gözde; Sarica, Ayse D.; Karaman, Gökçe; Tufan, Mümin; Bahap-Kudret, Zeynep; Zülfikar, Deniz

2016-01-01

The study aimed to examine the effectiveness of the Adapted Dialogic Reading Program (ADR) on the language and early literacy skills of Turkish kindergarteners from low socio-economic (SES) backgrounds. The effectiveness of ADR was investigated across six different treatment conditions including classroom and home based implementations in various…

Fuel cell technology program

NASA Technical Reports Server (NTRS)

1972-01-01

A program to advance the technology for a cost-effective hydrogen/oxygen fuel cell system for future manned spacecraft is discussed. The evaluation of base line design concepts and the development of product improvements in the areas of life, power, specific weight and volume, versatility of operation, field maintenance and thermal control were conducted from the material and component level through the fabrication and test of an engineering model of the fuel cell system. The program was to be accomplished in a 13 month period.

Programming Retinal Stem Cells into Cone Photoreceptors

DTIC Science & Technology

2015-12-01

AWARD NUMBER: W81XWH-14-1-0566 TITLE: Programming Retinal Stem Cells into Cone Photoreceptors PRINCIPAL INVESTIGATOR: Joseph A. Brzezinski IV...SUBTITLE 5a. CONTRACT NUMBER Programming Retinal Stem Cells into Cone Photoreceptors 5b. GRANT NUMBER W81XWH-14-1-0566 5c. PROGRAM ELEMENT NUMBER 6...to program human stem cells directly into cones. Using RNA-seq, we identified several genes that are upregulated in advance of the earliest

Navy DDG-51 and DDG-1000 Destroyer Programs: Background and Issues for Congress

DTIC Science & Technology

2016-05-20

within budget constraints. Navy officials stated that DDG- 51s can provide the area -defense AAW, BMD, and open-ocean ASW capabilities that the Navy wants...Navy DDG- 51 and DDG-1000 Destroyer Programs: Background and Issues for Congress Ronald O’Rourke Specialist in Naval Affairs May 20, 2016...

Programmed Cell Death During Caenorhabditis elegans Development

PubMed Central

Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

2016-01-01

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

PubMed Central

Cook, Matthew S.; Munger, Steven C.; Nadeau, Joseph H.; Capel, Blanche

2011-01-01

Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1Ter/Ter mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1Ter/Ter mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1Ter/Ter; Bax–/– double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1Ter/Ter germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27Kip1 and p21Cip1. P27Kip1 and P21Cip1 protein are both significantly decreased in Dnd1Ter/Ter germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility. PMID:21115610

Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice.

PubMed

Narahara, Shun; Matsushima, Haruna; Sakai, Eiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki

2012-04-01

Osteoclasts (OCLs) are multinucleated giant cells and are formed by the fusion of mononuclear progenitors of monocyte/macrophage lineage. It is known that macrophages derived from different genetic backgrounds exhibit quite distinct characteristics of immune responses. However, it is unknown whether OCLs from different genetic backgrounds show distinct characteristics. In this study, we showed that bone-marrow macrophages (BMMs) derived from C57BL/6, BALB/c and ddY mice exhibited considerably distinct morphological characteristics and cell differentiation into OCLs. The differentiation of BMMs into OCLs was comparatively quicker in the C57BL/6 and ddY mice, while that of BALB/c mice was rather slow. Morphologically, ddY OCLs showed a giant cell with a round shape, C57BL/6 OCLs were of a moderate size with many protrusions and BALB/c OCLs had the smallest size with fewer nuclei. The intracellular signaling of differentiation and expression levels of marker proteins of OCLs were different in the respective strains. Treatment of BMMs from the three different strains with the reducing agent N-acetylcysteine (NAC) or with the oxidation agent hydrogen peroxide (H(2)O(2)) induced changes in the shape and sizes of the cells and caused distinct patterns of cell differentiation and survival. Thus, genetic backgrounds and redox conditions regulate the morphological characteristics and cell differentiation of OCLs.

Background Underground at WIPP

NASA Astrophysics Data System (ADS)

Esch, Ernst-Ingo; Hime, A.; Bowles, T. J.

2001-04-01

Recent interest to establish a dedicated underground laboratory in the United States prompted an experimental program at to quantify the enviromental backgrounds underground at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. An outline of this program is provided along with recent experimental data on the cosmic ray muon flux at the 650 meter level of WIPP. The implications of the cosmic ray muon and fast neutron background at WIPP will be discussed in the context of new generation, low background experiments envisioned in the future.

Xylogenesis in zinnia (Zinnia elegans) cell cultures: unravelling the regulatory steps in a complex developmental programmed cell death event.

PubMed

Iakimova, Elena T; Woltering, Ernst J

2017-04-01

Physiological and molecular studies support the view that xylogenesis can largely be determined as a specific form of vacuolar programmed cell death (PCD). The studies in xylogenic zinnia cell culture have led to many breakthroughs in xylogenesis research and provided a background for investigations in other experimental models in vitro and in planta . This review discusses the most essential earlier and recent findings on the regulation of xylem elements differentiation and PCD in zinnia and other xylogenic systems. Xylogenesis (the formation of water conducting vascular tissue) is a paradigm of plant developmental PCD. The xylem vessels are composed of fused tracheary elements (TEs)-dead, hollow cells with patterned lignified secondary cell walls. They result from the differentiation of the procambium and cambium cells and undergo cell death to become functional post-mortem. The TE differentiation proceeds through a well-coordinated sequence of events in which differentiation and the programmed cellular demise are intimately connected. For years a classical experimental model for studies on xylogenesis was the xylogenic zinnia (Zinnia elegans) cell culture derived from leaf mesophyll cells that, upon induction by cytokinin and auxin, transdifferentiate into TEs. This cell system has been proven very efficient for investigations on the regulatory components of xylem differentiation which has led to many discoveries on the mechanisms of xylogenesis. The knowledge gained from this system has potentiated studies in other xylogenic cultures in vitro and in planta. The present review summarises the previous and latest findings on the hormonal and biochemical signalling, metabolic pathways and molecular and gene determinants underlying the regulation of xylem vessels differentiation in zinnia cell culture. Highlighted are breakthroughs achieved through the use of xylogenic systems from other species and newly introduced tools and analytical approaches to study the

Fuel cell technology program

NASA Technical Reports Server (NTRS)

1972-01-01

A fuel cell technology program was established to advance the state-of-the art of hydrogen oxygen fuel cells using low temperature, potassium hydroxide electrolyte technology as the base. Cell and component testing confirmed that low temperature, potassium hydroxide electrolyte technology is compatible with the requirements of the space shuttle Phase B contractors. Testing of the DM-1 powerplant demonstrated all of the important requirements of the shuttle except operating life. Testing also identified DM-1 powerplant life limiting mechanisms; hydrogen pump gear wear and pressurization of the cell stack over its design limits.

SAP modulates B cell functions in a genetic background-dependent manner.

PubMed

Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

2013-06-01

Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Status of shuttle fuel cell technology program.

NASA Technical Reports Server (NTRS)

Rice, W. E.; Bell, D., III

1972-01-01

The hydrogen-oxygen fuel cell has been proved as an efficient and reliable electrical power supply for NASA manned-space-flight vehicles. It has thus ensured a role in the Space Shuttle Program as the primary electrical power supply for the Orbiter vehicle. The advanced fuel cell technology programs conducted under the management of the NASA Manned Spacecraft Center over the past two years have resulted in a high level of technical readiness in fuel cell power generation to support shuttle mission requirements. These programs have taken advantage of technological developments that have occurred since the designs were completed for the Gemini and Apollo fuel cells.

Programming self-organizing multicellular structures with synthetic cell-cell signaling.

PubMed

Toda, Satoshi; Blauch, Lucas R; Tang, Sindy K Y; Morsut, Leonardo; Lim, Wendell A

2018-05-31

A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multi-domain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multi-cellularity and demonstrate the potential to engineer customized self-organizing tissues or materials. Copyright © 2018, American Association for the Advancement of Science.

Proteomic approach toward molecular backgrounds of drug resistance of osteosarcoma cells in spheroid culture system.

PubMed

Arai, Kazuya; Sakamoto, Ruriko; Kubota, Daisuke; Kondo, Tadashi

2013-08-01

Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than five cell lines and four species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the upregulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[The German program for disease management guidelines. Background, methods, and development process].

PubMed

Ollenschläger, Günter; Kopp, Ina; Lelgemann, Monika; Sänger, Sylvia; Heymans, Lothar; Thole, Henning; Trapp, Henrike; Lorenz, Wilfried; Selbmann, Hans-Konrad; Encke, Albrecht

2006-10-15

The Program for National Disease Management Guidelines (German DM-CPG Program) was established in 2002 by the German Medical Association (umbrella organization of the German Chambers of Physicians) and joined by the Association of the Scientific Medical Societies (AWMF; umbrella organization of more than 150 professional societies) and by the National Association of Statutory Health Insurance Physicians (NASHIP) in 2003. The program provides a conceptual basis for disease management, focusing on high-priority health-care topics and aiming at the implementation of best practice recommendations for prevention, acute care, rehabilitation and chronic care. It is organized by the German Agency for Quality in Medicine, a founding member of the Guidelines International Network (G-I-N). The main objective of the German DM-CPG Program is to establish consensus of the medical professions on evidence-based key recommendations covering all sectors of health-care provision and facilitating the coordination of care for the individual patient through time and across interfaces. Within the last year, DM-CPGs have been published for asthma, chronic obstructive pulmonary disease, type 2 diabetes, and coronary heart disease. In addition, experts from national patient self-help groups have been developing patient guidance based upon the recommendations for health-care providers. The article describes background, methods, and tools of the DM-CPG Program, and is the first of a publication series dealing with innovative recommendations and aspects of the program.

Reducing WBC background in cancer cell separation products by negative acoustic contrast particle immuno-acoustophoresis.

PubMed

Cushing, Kevin; Undvall, Eva; Ceder, Yvonne; Lilja, Hans; Laurell, Thomas

2018-02-13

Cancer cells display acoustic properties enabling acoustophoretic separation from white blood cells (WBCs) with 2-3 log suppression of the WBC background. However, a subset of WBCs has overlapping acoustic properties with cancer cells, which is why label-free acoustophoretic cancer cell isolation needs additional purification prior to analysis. This paper reports for the first time a proof of concept for continuous flow acoustophoretic negative selection of WBCs from cancer cells using negative acoustic contrast elastomeric particles (EPs) activated with CD45-antibodies that specifically bind to WBCs. The EP/WBC complexes align at the acoustic pressure anti-nodes along the channel walls while unbound cancer cells focus to the pressure node in the channel center, enabling continuous flow based depletion of WBC background in a cancer cell product. The method does not provide a single process solution for the CTC separation challenge, but provides an elegant part to a multi-step process by further reducing the WBC background in cancer cell separation products derived from an initial step of label-free acoustophoresis. We report the recorded performance of the negative selection immuno-acoustophoretic WBC depletion and cancer cell recovery. To eliminate the negative impact of the separation due to the known problems of aggregation of negative acoustic contrast particles along the sidewalls of the acoustophoresis channel and to enable continuous separation of EP/WBC complexes from cancer cells, a new acoustic actuation method has been implemented where the ultrasound frequency is scanned (1.991MHz ± 100 kHz, scan rate 200 kHz ms -1 ). Using this frequency scanning strategy EP/WBC complexes were acoustophoretically separated from mixtures of WBCs spiked with breast and prostate cancer cells (DU145 and MCF-7). An 86-fold (MCF-7) and 52-fold (DU145) reduction of WBCs in the cancer cell fractions were recorded with separation efficiencies of 98.6% (MCF-7) and 99

NASA's lithium cell technology program

NASA Technical Reports Server (NTRS)

Juvinall, G. L.

1978-01-01

Briefly outlined are the activities of the various research centers involved in the NASA program. Graphs are presented for: (1) the initial results on SOCl2 decomposition rate; (2) effect of rate on output of Li-SOCl2 cells; (3) comparison of high and low rate Li-SOCl2 cells; and (4) effect of temperature on output of Li-SOCl2 cells. Abusive test results and a description of secondary lithium cells are also presented.

Air Force Ni-Cd cell qualification program update

NASA Technical Reports Server (NTRS)

Hall, Steve; Brown, Harry; Collins, G.; Hwang, W.; Bui, Q.

1993-01-01

The generic qualification of aerospace nickel-cadmium cells is discussed. The test program includes the following: all available manufacturers, all available designs, cells from the previous program, and high and low orbit life cycling. It is the purpose of this program to characterize the beginning of life performance.

CELLFS: TAKING THE "DMA" OUT OF CELL PROGRAMMING

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

IONKOV, LATCHESAR A.; MIRTCHOVSKI, ANDREY A.; NYRHINEN, AKI M.

In this paper we present a new programming model for the Cell BE architecture of scalar multiprocessors. They call this programming model CellFS. CellFS aims at simplifying the task of managing I/O between the local store of the processing units and main memory. The CellFS support library provides the means for transferring data via simple file I/O operations between the PPU and the SPU.

Evaluation program for secondary spacecraft cells

NASA Technical Reports Server (NTRS)

Christy, D. E.

1972-01-01

The life cycle test of secondary spacecraft electric cells is discussed. The purpose of the tests is to insure that all cells put into the life cycle test meet the required specifications. The evaluation program gathers statistical information concerning cell performance characteristics and limitations. Weaknesses in cell design which are discovered during the tests are reported to research facilities in order to increase the service life of the cells.

Background fluorescence estimation and vesicle segmentation in live cell imaging with conditional random fields.

PubMed

Pécot, Thierry; Bouthemy, Patrick; Boulanger, Jérôme; Chessel, Anatole; Bardin, Sabine; Salamero, Jean; Kervrann, Charles

2015-02-01

Image analysis applied to fluorescence live cell microscopy has become a key tool in molecular biology since it enables to characterize biological processes in space and time at the subcellular level. In fluorescence microscopy imaging, the moving tagged structures of interest, such as vesicles, appear as bright spots over a static or nonstatic background. In this paper, we consider the problem of vesicle segmentation and time-varying background estimation at the cellular scale. The main idea is to formulate the joint segmentation-estimation problem in the general conditional random field framework. Furthermore, segmentation of vesicles and background estimation are alternatively performed by energy minimization using a min cut-max flow algorithm. The proposed approach relies on a detection measure computed from intensity contrasts between neighboring blocks in fluorescence microscopy images. This approach permits analysis of either 2D + time or 3D + time data. We demonstrate the performance of the so-called C-CRAFT through an experimental comparison with the state-of-the-art methods in fluorescence video-microscopy. We also use this method to characterize the spatial and temporal distribution of Rab6 transport carriers at the cell periphery for two different specific adhesion geometries.

A low-background piston-cylinder-type hybrid high pressure cell for muon-spin rotation/relaxation experiments

NASA Astrophysics Data System (ADS)

Shermadini, Z.; Khasanov, R.; Elender, M.; Simutis, G.; Guguchia, Z.; Kamenev, K. V.; Amato, A.

2017-10-01

A low background double-wall piston-cylinder-type pressure cell is developed at the Paul Scherrer Institute. The cell is made from BERYLCO-25 (beryllium copper) and MP35N nonmagnetic alloys with the design and dimensions which are specifically adapted to muon-spin rotation/relaxation (μSR) measurements. The mechanical design and performance of the pressure cell are evaluated using finite-element analysis (FEA). By including the measured stress-strain characteristics of the materials into the finite-element model, the cell dimensions are optimized with the aim to reach the highest possible pressure while maintaining the sample space large (6 mm in diameter and 12 mm high). The presented unconventional design of the double-wall piston-cylinder pressure cell with a harder outer MP35N sleeve and a softer inner CuBe cylinder enables pressures of up to 2.6 GPa to be reached at ambient temperature, corresponding to 2.2 GPa at low temperatures without any irreversible damage to the pressure cell. The nature of the muon stopping distribution, mainly in the sample and in the CuBe cylinder, results in a low-background μSR signal.

CIF2Cell: Generating geometries for electronic structure programs

NASA Astrophysics Data System (ADS)

Björkman, Torbjörn

2011-05-01

The CIF2Cell program generates the geometrical setup for a number of electronic structure programs based on the crystallographic information in a Crystallographic Information Framework (CIF) file. The program will retrieve the space group number, Wyckoff positions and crystallographic parameters, make a sensible choice for Bravais lattice vectors (primitive or principal cell) and generate all atomic positions. Supercells can be generated and alloys are handled gracefully. The code currently has output interfaces to the electronic structure programs ABINIT, CASTEP, CPMD, Crystal, Elk, Exciting, EMTO, Fleur, RSPt, Siesta and VASP. Program summaryProgram title: CIF2Cell Catalogue identifier: AEIM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEIM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU GPL version 3 No. of lines in distributed program, including test data, etc.: 12 691 No. of bytes in distributed program, including test data, etc.: 74 933 Distribution format: tar.gz Programming language: Python (versions 2.4-2.7) Computer: Any computer that can run Python (versions 2.4-2.7) Operating system: Any operating system that can run Python (versions 2.4-2.7) Classification: 7.3, 7.8, 8 External routines: PyCIFRW [1] Nature of problem: Generate the geometrical setup of a crystallographic cell for a variety of electronic structure programs from data contained in a CIF file. Solution method: The CIF file is parsed using routines contained in the library PyCIFRW [1], and crystallographic as well as bibliographic information is extracted. The program then generates the principal cell from symmetry information, crystal parameters, space group number and Wyckoff sites. Reduction to a primitive cell is then performed, and the resulting cell is output to suitably named files along with documentation of the information source generated from any bibliographic information contained in the CIF

78 FR 44575 - Sickle Cell Disease Treatment Demonstration Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Sickle Cell... Extension: Sickle Cell Disease Treatment Demonstration Program (U1E) Awards to Three Currently Funded... the Sickle Cell Disease Treatment Demonstration Program. Three of these awards will end on August 31...

Plasma membrane changes during programmed cell deaths

PubMed Central

Zhang, Yingying; Chen, Xin; Gueydan, Cyril; Han, Jiahuai

2018-01-01

Ruptured and intact plasma membranes are classically considered as hallmarks of necrotic and apoptotic cell death, respectively. As such, apoptosis is usually considered a non-inflammatory process while necrosis triggers inflammation. Recent studies on necroptosis and pyroptosis, two types of programmed necrosis, revealed that plasma membrane rupture is mediated by MLKL channels during necroptosis but depends on non-selective gasdermin D (GSDMD) pores during pyroptosis. Importantly, the morphology of dying cells executed by MLKL channels can be distinguished from that executed by GSDMD pores. Interestingly, it was found recently that secondary necrosis of apoptotic cells, a previously believed non-regulated form of cell lysis that occurs after apoptosis, can be programmed and executed by plasma membrane pore formation like that of pyroptosis. In addition, pyroptosis is associated with pyroptotic bodies, which have some similarities to apoptotic bodies. Therefore, different cell death programs induce distinctive reshuffling processes of the plasma membrane. Given the fact that the nature of released intracellular contents plays a crucial role in dying/dead cell-induced immunogenicity, not only membrane rupture or integrity but also the nature of plasma membrane breakdown would determine the fate of a cell as well as its ability to elicit an immune response. In this review, we will discuss recent advances in the field of apoptosis, necroptosis and pyroptosis, with an emphasis on the mechanisms underlying plasma membrane changes observed on dying cells and their implication in cell death-elicited immunogenicity. PMID:29076500

A Preventive Intervention Program for Urban African American Youth Attending an Alternative Education Program: Background, Implementation, and Feasibility.

PubMed

Carswell, Steven B; Hanlon, Thomas E; O'Grady, Kevin E; Watts, Amy M; Pothong, Pattarapan

2009-01-01

This paper presents background, implementation, and feasibility findings associated with planning and conducting an after-school intervention program in an alternative education setting designed to prevent the initiation and escalation of violence and substance abuse among urban African American youth at high risk for life-long problem behaviors. Evolving from earlier preventive interventions implemented in clinic and school settings, the program, entitled The Village Model of Care, consisted of structured group mentoring, parental support, and community outreach services administered to alternative education students and their primary caregiver(s) during the school year. Over a two-year intake period, 109 youth participated in the present process evaluation study. Findings from the study not only provided relevant demographic information on the characteristics of youth likely to be included in such programs but also indicated the importance of including the family in the rehabilitation effort and the need for school administrative system support for the underlying alternative education approach. The information presented in this report has a direct bearing on the planning of future prevention efforts conducted in similar settings that are aimed at reducing problem behaviors and promoting positive lifestyles among high-risk youth.

1986 fuel cell seminar: Program and abstracts

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

None

1986-10-01

Ninety nine brief papers are arranged under the following session headings: gas industry's 40 kw program, solid oxide fuel cell technology, phosphoric acid fuel cell technology, molten carbonate fuel cell technology, phosphoric acid fuel cell systems, power plants technology, fuel cell power plant designs, unconventional fuels, fuel cell application and economic assessments, and plans for commerical development. The papers are processed separately for the data base. (DLC)

Commentary: "re-programming or selecting adult stem cells?".

PubMed

Trosko, James E

2008-01-01

The recent observations that embryonic stemness-associated genes could assist in the "de-differentiation" of adult skin fibroblast cells to "embryonic-like stem cells", using the "somatic cell nuclear transfer" techniques, have been interpreted as indicating a "re-programming" of genes. These reports have demonstrated a "proof of principle" approach to by-pass many, but not all, of the ethical, scientific and medical limitations of the "therapeutic cloning" of embryonic stem cells from embryos. However, while the interpretation that real "re-programming" of all those somatic fibroblastic differentiation genes might be correct, there does exists an alternative hypothesis of these exciting results. Based on the fact that multipotent adult stem cells exist in most, if not all, adult organs, the possibility exists that all these recent "re-programming" results, using the somatic nuclear transfer techniques, actually were the results of transferred rare nuclear material from the adult stem cells residing in the skin of the mouse, monkey and human samples. An examination of the rationale for this challenging hypothesis has been drawn from the hypothesis of the "stem cell theory of cancer", as well as from the field of human adult stem cells research.

Nickel-Cadmium Cell Design Variable Program Data Analysis

NASA Technical Reports Server (NTRS)

Morrow, G. W.

1985-01-01

A program was undertaken in conjunction with the General Electric Company to evaluate 9 of the more important nickel cadmium aerospace cell designs that are currently being used or that have been used in the past 15 years. Design variables tested in this program included teflonated negative plates, silver treated negative plates, light plate loading level, no positive plate cadmium treatment, plate design of 1968 utilizing both old and new processing techniques, and electrochemically impregnated positive plates. The data acquired from these test packs in a low Earth orbit cycling regime is presented and analyzed here. This data showed conclusively that the cells manufactured with no positive plate cadmium treatment outperformed all other cell designs in all aspects of the program and that the cells with teflonated negative electrodes performed very poorly.

Background ELF magnetic fields in incubators: a factor of importance in cell culture work.

PubMed

Mild, Kjell Hansson; Wilén, Jonna; Mattsson, Mats-Olof; Simko, Myrtill

2009-07-01

Extremely low frequency (ELF) magnetic fields in cell culture incubators have been measured. Values of the order of tens of muT were found which is in sharp contrast to the values found in our normal environment (0.05-0.1microT). There are numerous examples of biological effects found after exposure to MF at these levels, such as changes in gene expression, blocked cell differentiation, inhibition of the effect of tamoxifen, effects on chick embryo development, etc. We therefore recommend that people working with cell culture incubators check for the background magnetic field and take this into account in performing their experiments, since this could be an unrecognised factor of importance contributing to the variability in the results from work with cell cultures.

Programmed cell death as a defence against infection

PubMed Central

Jorgensen, Ine; Rayamajhi, Manira; Miao, Edward A.

2017-01-01

Eukaryotic cells can die from physical trauma, resulting in necrosis. Alternately, they can die via programmed cell death upon stimulation of specific signalling pathways. Here we discuss the utility of four cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary arms race with pathogens. Finally, we describe how the resulting cell corpses — apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) — promote clearance of infection. PMID:28138137

Mastoparan-induced programmed cell death in the unicellular alga Chlamydomonas reinhardtii

PubMed Central

Yordanova, Zhenya P.; Woltering, Ernst J.; Kapchina-Toteva, Veneta M.; Iakimova, Elena T.

2013-01-01

Background and Aims Under stress-promoting conditions unicellular algae can undergo programmed cell death (PCD) but the mechanisms of algal cellular suicide are still poorly understood. In this work, the involvement of caspase-like proteases, DNA cleavage and the morphological occurrence of cell death in wasp venom mastoparan (MP)-treated Chlamydomonas reinhardtii were studied. Methods Algal cells were exposed to MP and cell death was analysed over time. Specific caspase inhibitors were employed to elucidate the possible role of caspase-like proteases. YVADase activity (presumably a vacuolar processing enzyme) was assayed by using a fluorogenic caspase-1 substrate. DNA breakdown was evaluated by DNA laddering and Comet analysis. Cellular morphology was examined by confocal laser scanning microscopy. Key Results MP-treated C. reinhardtii cells expressed several features of necrosis (protoplast shrinkage) and vacuolar cell death (lytic vesicles, vacuolization, empty cell-walled corpse-containing remains of digested protoplast) sometimes within one single cell and in different individual cells. Nucleus compaction and DNA fragmentation were detected. YVADase activity was rapidly stimulated in response to MP but the early cell death was not inhibited by caspase inhibitors. At later time points, however, the caspase inhibitors were effective in cell-death suppression. Conditioned medium from MP-treated cells offered protection against MP-induced cell death. Conclusions In C. reinhardtii MP triggered PCD of atypical phenotype comprising features of vacuolar and necrotic cell deaths, reminiscent of the modality of hypersensitive response. It was assumed that depending on the physiological state and sensitivity of the cells to MP, the early cell-death phase might be not mediated by caspase-like enzymes, whereas later cell death may involve caspase-like-dependent proteolysis. The findings substantiate the hypothesis that, depending on the mode of induction and sensitivity of

Five C Framework: A Student-Centered Approach for Teaching Programming Courses to Students with Diverse Disciplinary Background

ERIC Educational Resources Information Center

Tom, Mary

2015-01-01

The already existing complexities of teaching and learning computer programming are increased where students are diverse in their disciplinary backgrounds, language skills, and culture. Learners experience emotional issues of anxiety, fear or boredom. Identifying opportunities for improvement and applying theoretical and empirical evidence found…

Temporal competition between differentiation programs determines cell fate choice

NASA Astrophysics Data System (ADS)

Kuchina, Anna; Espinar, Lorena; Cagatay, Tolga; Balbin, Alejandro; Alvarado, Alma; Garcia-Ojalvo, Jordi; Suel, Gurol

2011-03-01

During pluripotent differentiation, cells adopt one of several distinct fates. The dynamics of this decision-making process are poorly understood, since cell fate choice may be governed by interactions between differentiation programs that are active at the same time. We studied the dynamics of decision-making in the model organism Bacillus subtilis by simultaneously measuring the activities of competing differentiation programs (sporulation and competence) in single cells. We discovered a precise switch-like point of cell fate choice previously hidden by cell-cell variability. Engineered artificial crosslinks between competence and sporulation circuits revealed that the precision of this choice is generated by temporal competition between the key players of two differentiation programs. Modeling suggests that variable progression towards a switch-like decision might represent a general strategy to maximize adaptability and robustness of cellular decision-making.

A Mentor Training Program Improves Mentoring Competency for Researchers Working with Early-Career Investigators from Underrepresented Backgrounds

ERIC Educational Resources Information Center

Johnson, Mallory O.; Gandhi, Monica

2015-01-01

Mentoring is increasingly recognized as a critical element in supporting successful careers in academic research in medicine and related disciplines, particularly for trainees and early career investigators from underrepresented backgrounds. Mentoring is often executed ad hoc; there are limited programs to train faculty to become more effective…

Special Education in Hong Kong: Background, Contemporary Trends and Issues in Programs for Learners with Disabilities

ERIC Educational Resources Information Center

Lian, Ming-Gon John; Tse, Andrew Chung-yee; Li, Alison Man Ching

2007-01-01

Since the handover of the sovereignty from the United Kingdom to the People's Republic of China in 1997, there have been a series of change, development, and related issues in special education programs for learners with disabilities in Hong Kong. In this paper, we try to describe the background and recent trends, issues, and implications that…

Mitochondrial fission proteins regulate programmed cell death in yeast.

PubMed

Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J; Qi, Bing; Pevsner, Jonathan; McCaffery, J Michael; Hill, R Blake; Basañez, Gorka; Hardwick, J Marie

2004-11-15

The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function.

Navy-Marine Corps Amphibious and Maritime Prepositioning Ship Programs: Background and Oversight Issues for Congress

DTIC Science & Technology

2007-06-12

up Northrop Grumman Ship Systems ( NGSS ). Table 2. FY2008-FY2013 Amphibious and MPF(F) Ship Procurement Plan (Ships fully funded in FY2006 shown for... Plan . . 13 Navy-Marine Corps Amphibious and Maritime Prepositioning Ship Programs: Background and Oversight Issues for Congress Introduction The...is whether to approve, modify, or reject the Navy’s plans for procuring amphibious and MPF(F) ships. Decisions that Congress makes on this CRS-2 1 The

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetically programmed superparamagnetic behavior of mammalian cells.

PubMed

Kim, Taeuk; Moore, David; Fussenegger, Martin

2012-12-31

Although magnetic fields and paramagnetic inorganic materials were abundant on planet earth during the entire evolution of living species the interaction of organisms with these physical forces remains a little-understood phenomenon. Interestingly, rather than being genetically encoded, organisms seem to accumulate and take advantage of inorganic nanoparticles to sense or react to magnetic fields. Using a synthetic biology-inspired approach we have genetically programmed mammalian cells to show superparamagnetic behavior. The combination of ectopic production of the human ferritin heavy chain 1 (hFTH1), engineering the cells for expression of an iron importer, the divalent metal ion transferase 1 (DMT1) and the design of an iron-loading culture medium to maximize cellular iron uptake enabled efficient iron mineralization in intracellular ferritin particles and conferred superparamagnetic behavior to the entire cell. When captured by a magnetic field the superparamagnetic cells reached attraction velocities of up to 30 μm/s and could be efficiently separated from complex cell mixtures using standard magnetic cell separation equipment. Technology that enables magnetic separation of genetically programmed superparamagnetic cells in the absence of inorganic particles could foster novel opportunities in diagnostics and cell-based therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

Fuel cell systems program plan, FY 1990

NASA Astrophysics Data System (ADS)

1989-10-01

A principal goal of the Office of Fossil Energy is to increase the utilization of domestic fuels in an environmentally benign manner, through the development and transfer to the private sector of advanced energy conversion technology. Successful efforts to achieve this goal contribute to the stability and reliability of reasonably priced energy supplies, enhance the competitiveness of domestic fuels and energy technologies in domestic and international markets, and contribute to the development of cost effective strategies for control of acid rain and global warming. Several advanced energy conversion technologies are now under development by DOE which can help to achieve these objectives. Fuel cells are among those technologies. This report briefly describes fuel cell technology and the program plan of U.S. DOE fuel cell program.

Grid-Optimization Program for Photovoltaic Cells

NASA Technical Reports Server (NTRS)

Daniel, R. E.; Lee, T. S.

1986-01-01

CELLOPT program developed to assist in designing grid pattern of current-conducting material on photovoltaic cell. Analyzes parasitic resistance losses and shadow loss associated with metallized grid pattern on both round and rectangular solar cells. Though performs sensitivity studies, used primarily to optimize grid design in terms of bus bar and grid lines by minimizing power loss. CELLOPT written in APL.

Navy Columbia Class (Ohio Replacement) Ballistic Missile Submarine (SSBN[X]) Program: Background and Issues for Congress

DTIC Science & Technology

2016-08-18

of UK design and manufacture . 12 For more on the arrangement for jointly building Virginia- class boats, see CRS Report RL32418, Navy Virginia (SSN...schedule reduction in Missile Tube Module manufacturing for the OR Class . This schedule reduction, on a potential critical path assembly, would reduce...Navy Columbia Class (Ohio Replacement) Ballistic Missile Submarine (SSBN[X]) Program: Background and Issues for Congress Ronald O’Rourke

Fuel cell energy service Enron`s commerical program

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

Jacobson, M.W.

1996-04-01

Enron, the premier provider of clean fuels worldwide, has launched a unique energy service based on fuel cell technology. The goal of this program is to bring the benefits of fuel cell power to the broad commercial marketplace. Enron`s Energy Service is currently based on a 200 kilowatt phosphoric acid power plant manufactured by ONSI Corporation. This plant is fueled by natural gas or propane, and exhibits superior performance. Enron offers a `no hassle` package that provides customers with immediate benefits with no upfront capital or technical risks. This paper describes Enron`s fuel cell commercial program.

Fuel cell technology program contract summary report

NASA Technical Reports Server (NTRS)

1972-01-01

A fuel cell technology program which was established to advance the state-of-the-art of hydrogen-oxygen fuel cells using the P and WA PC8B technology as the base is reported. The major tasks of this program consisted of (1) fuel cell system studies of a space shuttle powerplant conceptual design (designated engineering model -1, EM-1) supported by liaison with the space shuttle prime contractors; (2) component and subsystem technology advancement and; (3) a demonstrator powerplant test. Fuel cell system studies, with the EM-1 as the focal point of design activities, included determination of voltage regulation, specific reactant consumption, weight, voltage level and performance characteristics. These studies provided the basis for coordination activities with the space shuttle vehicle prime contractor. Interface information, on-board checkout and in-flight monitoring requirements, and development cost data were also provided as part of this activity. Even though the two vehicles primes had different voltage requirements (115 volts in one case and 28 volts in the other), it was concluded that either option could be provided in the fuel cell power system by the electrical hook-up of the cells in the stack.

14 CFR 91.1051 - Pilot safety background check.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Pilot safety background check. 91.1051... Operations Program Management § 91.1051 Pilot safety background check. Within 90 days of an individual beginning service as a pilot, the program manager must request the following information: (a) FAA records...

Highly sensitive low-background fluorescent probes for imaging of nitric oxide in cells and tissues.

PubMed

Zhang, Hui-Xian; Chen, Jian-Bo; Guo, Xiao-Feng; Wang, Hong; Zhang, Hua-Shan

2014-03-18

Small-molecule fluorescent probes in combination with fluorescent microscopy can be a powerful tool to provide real-time detection and high spatiotemporal resolution of transient molecules in cells and bodies. For the design of fluorescent probes for transient molecule imaging, high detection sensitivity is crucial. In this report, two new fluorescent probes, 8-(3,4-diaminophenyl)-4,4-difluoro-4-bora-3a,4a-diaza-di(1,2-dihydro)naphtho[b,g]-s-indacene (DANPBO-H) and 8-(3,4-diaminophenyl)-1,7-dimethyl-4,4-difluoro-4-bora-3a,4a-diaza-di(1,2-dihydro)naphtho[b,g]-s-indacene (DANPBO-M), have been developed for nitric oxide (NO) imaging. The detection sensitivity has been efficiently improved by use of these probes through increasing NO detection signals and decreasing background fluorescence. Fluorescence in the far-red region is enhanced by 400- and 550-fold after reaction with NO is achieved and remains stable for at least 24 h under the irradiation of xenon lamp. Excitation and emission wavelengths longer than 600 nm and excellent intracellular retention of these probes and their NO products create dark background inside and outside cells and tissues. What is more, the excellent intracellular retention of these compounds is obtained by their strong lipophilicity, which is a novel design concept diametrically opposite to the traditional approaches. The high sensitivity and dark background make DANPBO-H and DANPBO-M competitive for NO imaging in cells and tissues. The lipophilicity-based intracellular retention mechanism as a design strategy has great potential in the development of fluorescent probes for bioimaging.

Aerospace nickel-cadmium cell separator qualifications program

NASA Technical Reports Server (NTRS)

Francis, R. W.; Haag, R. L.

1986-01-01

The present space qualified nylon separator, Pellon 2505 ML, is no longer available for aerospace nickel-cadmium (NiCd) cells. As a result of this anticipated unavailability, a joint Government program between the Air Force Space Division and the Naval Research Laboratory was established. Four cell types were procured with both the old qualified and the new unqualified separators. Acceptance, characterization, and life cycling tests are to be performed at the Naval Weapons Support Center, Crane, Ind. (NWSC/Crane). The scheduling and current status of this program are discussed and the progress of testing and available results are projected.

Navy Columbia Class (Ohio Replacement) Ballistic Missile Submarine (SSBN[X]) Program: Background and Issues for Congress

DTIC Science & Technology

2016-10-03

of UK design and manufacture . 12 For more on the arrangement for jointly building Virginia- class boats, see CRS Report RL32418, Navy Virginia (SSN...lines would result in a cumulative one year schedule reduction in Missile Tube Module manufacturing for the OR Class . This schedule reduction, on a...Navy Columbia Class (Ohio Replacement) Ballistic Missile Submarine (SSBN[X]) Program: Background and Issues for Congress Ronald O’Rourke

Dysregulation of haematopoietic stem cell regulatory programs in acute myeloid leukaemia.

PubMed

Basilico, Silvia; Göttgens, Berthold

2017-07-01

Haematopoietic stem cells (HSC) are situated at the apex of the haematopoietic differentiation hierarchy, ensuring the life-long supply of mature haematopoietic cells and forming a reservoir to replenish the haematopoietic system in case of emergency such as acute blood loss. To maintain a balanced production of all mature lineages and at the same time secure a stem cell reservoir, intricate regulatory programs have evolved to control multi-lineage differentiation and self-renewal in haematopoietic stem and progenitor cells (HSPCs). Leukaemogenic mutations commonly disrupt these regulatory programs causing a block in differentiation with simultaneous enhancement of proliferation. Here, we briefly summarize key aspects of HSPC regulatory programs, and then focus on their disruption by leukaemogenic fusion genes containing the mixed lineage leukaemia (MLL) gene. Using MLL as an example, we explore important questions of wider significance that are still under debate, including the importance of cell of origin, to what extent leukaemia oncogenes impose specific regulatory programs and the relevance of leukaemia stem cells for disease development and prognosis. Finally, we suggest that disruption of stem cell regulatory programs is likely to play an important role in many other pathologies including ageing-associated regenerative failure.

Space Station Freedom NiH2 cell testing program

NASA Technical Reports Server (NTRS)

Moore, Bruce; Frate, Dave

1994-01-01

Testing for the Space Station Freedom Nickel Hydrogen Cell Test Program began in 1990 at Crave Division, Naval Surface Warfare Center. The program has included receipt inspection, random vibration, acceptance, characterization, and life cycle testing of Ni-H2 cells in accordance with the NASA LeRC Interagency Order C-31001-J. A total of 400 Ni-H2 cells have been received at NAVSURFWARCENDIV Crane from three separate manufacturers; Yardney Technical Products (Yardney), Eagle Picher Industries (Eagle Picher), and Gates Energy Products (Gates). Of those, 308 cells distributed among 39 packs have undergone life cycle testing under a test regime simulating low earth orbit conditions. As of 30 September 1993, there are 252 cells assembled into 32 packs still on life cycle test. Since the beginning of the program, failed cells have been detected in all phases of testing. The failures include the following; seven 65 AmpHr and 81 AmpHr Yardney cells were found to be leaking KOH on receipt, one 65 AmpHr Eagle Picher cell failed the acceptance test, one 65 AmpHr Gates cell failed during the characterization test, and six 65 AmpHr Gates cells failed the random vibration test. Of the 39 life cycle packs, testing on seven packs, 56 cells, has been suspended because of low end of discharge voltages. All of the failed life cycle packs were cycled at 60% depth of discharge.

Specific Cell (Re-)Programming: Approaches and Perspectives.

PubMed

Hausburg, Frauke; Jung, Julia Jeannine; David, Robert

2018-01-01

Many disorders are manifested by dysfunction of key cell types or their disturbed integration in complex organs. Thereby, adult organ systems often bear restricted self-renewal potential and are incapable of achieving functional regeneration. This underlies the need for novel strategies in the field of cell (re-)programming-based regenerative medicine as well as for drug development in vitro. The regenerative field has been hampered by restricted availability of adult stem cells and the potentially hazardous features of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Moreover, ethical concerns and legal restrictions regarding the generation and use of ESCs still exist. The establishment of direct reprogramming protocols for various therapeutically valuable somatic cell types has overcome some of these limitations. Meanwhile, new perspectives for safe and efficient generation of different specified somatic cell types have emerged from numerous approaches relying on exogenous expression of lineage-specific transcription factors, coding and noncoding RNAs, and chemical compounds.It should be of highest priority to develop protocols for the production of mature and physiologically functional cells with properties ideally matching those of their endogenous counterparts. Their availability can bring together basic research, drug screening, safety testing, and ultimately clinical trials. Here, we highlight the remarkable successes in cellular (re-)programming, which have greatly advanced the field of regenerative medicine in recent years. In particular, we review recent progress on the generation of cardiomyocyte subtypes, with a focus on cardiac pacemaker cells. Graphical Abstract.

Naval Research Laboratory's programs in advanced indium phosphide solar cell development

NASA Technical Reports Server (NTRS)

Summers, Geoffrey P.

1995-01-01

The Naval Research Laboratory has been involved in developing InP solar cell technology since 1988. The purpose of these programs was to produce advanced cells for use in very high radiation environments, either as a result of operating satellites in the Van Allen belts or for very long duration missions in other orbits. Richard Statler was technical representative on the first program, with Spire Corporation as the contractor, which eventually produced several hundred, high efficiency 2 x 2 sq cm single crystal InP cells. The shallow homojunction technology which was developed in this program enabled cells to be made with AMO, one sun efficiencies greater than 19%. Many of these cells have been flown on space experiments, including PASP Plus, which have confirmed the high radiation resistance of InP cells. NRL has also published widely on the radiation response of these cells and also on radiation-induced defect levels detected by DLTS, especially the work of Rob Walters and Scott Messenger. In 1990 NRL began another Navy-sponsored program with Tim Coutts and Mark Wanlass at the National Renewable Energy Laboratory (NREL), to develop a one sun, two terminal space version of the InP-InGaAs tandem junction cell being investigated at NREL for terrestrial applications. These cells were grown on InP substrates. Several cells with AM0, one sun efficiencies greater than 22% were produced. Two 2 x 2 sq cm cells were incorporated on the STRV lA/B solar cell experiment. These were the only two junction, tandem cells on the STRV experiment. The high cost and relative brittleness of InP wafers meant that if InP cell technology were to become a viable space power source, the superior radiation resistance of InP would have to be combined with a cheaper and more robust substrate. The main technical challenge was to overcome the effect of the dislocations produced by the lattice mismatch at the interface of the two materials. Over the last few years, NRL and Steve Wojtczuk at

Ba2+- and bupivacaine-sensitive background K+ conductances mediate rapid EPSP attenuation in oligodendrocyte precursor cells

PubMed Central

Chan, Chu-Fang; Kuo, Tzu-Wei; Weng, Ju-Yun; Lin, Yen-Chu; Chen, Ting-Yu; Cheng, Jen-Kun; Lien, Cheng-Chang

2013-01-01

Glutamatergic transmission onto oligodendrocyte precursor cells (OPCs) may regulate OPC proliferation, migration and differentiation. Dendritic integration of excitatory postsynaptic potentials (EPSPs) is critical for neuronal functions, and mechanisms regulating dendritic propagation and summation of EPSPs are well understood. However, little is known about EPSP attenuation and integration in OPCs. We developed realistic OPC models for synaptic integration, based on passive membrane responses of OPCs obtained by simultaneous dual whole-cell patch-pipette recordings. Compared with neurons, OPCs have a very low value of membrane resistivity, which is largely mediated by Ba2+- and bupivacaine-sensitive background K+ conductances. The very low membrane resistivity not only leads to rapid EPSP attenuation along OPC processes but also sharpens EPSPs and narrows the temporal window for EPSP summation. Thus, background K+ conductances regulate synaptic responses and integration in OPCs, thereby affecting activity-dependent neuronal control of OPC development and function. PMID:23940377

The US Army Foreign Comparative Test fuel cell program

NASA Astrophysics Data System (ADS)

Bostic, Elizabeth; Sifer, Nicholas; Bolton, Christopher; Ritter, Uli; Dubois, Terry

The US Army RDECOM initiated a Foreign Comparative Test (FCT) Program to acquire lightweight, high-energy dense fuel cell systems from across the globe for evaluation as portable power sources in military applications. Five foreign companies, including NovArs, Smart Fuel Cell, Intelligent Energy, Ballard Power Systems, and Hydrogenics, Inc., were awarded competitive contracts under the RDECOM effort. This paper will report on the status of the program as well as the experimental results obtained from one of the units. The US Army has interests in evaluating and deploying a variety of fuel cell systems, where these systems show added value when compared to current power sources in use. For low-power applications, fuel cells utilizing high-energy dense fuels offer significant weight savings over current battery technologies. This helps reduce the load a solider must carry for longer missions. For high-power applications, the low operating signatures (acoustic and thermal) of fuel cell systems make them ideal power generators in stealth operations. Recent testing has been completed on the Smart Fuel Cell A25 system that was procured through the FCT program. The "A-25" is a direct methanol fuel cell hybrid and was evaluated as a potential candidate for soldier and sensor power applications.

Fuel cell technology program

NASA Technical Reports Server (NTRS)

1971-01-01

The results of a solid polymer electrolyte fuel cell development program are summarized. A base line design was defined, and materials and components of the base line configuration were fabricated and tested. Concepts representing base line capability extensions in the areas of life, power, specific weight and volume, versatility of operation, field maintenance, and thermal control were identified and evaluated. Liaison and coordination with space shuttle contractors resulted in the exchange of engineering data.

Chemokine programming dendritic cell antigen response: part II - programming antigen presentation to T lymphocytes by partially maintaining immature dendritic cell phenotype.

PubMed

Park, Jaehyung; Bryers, James D

2013-05-01

In a companion article to this study,(1) the successful programming of a JAWSII dendritic cell (DC) line's antigen uptake and processing was demonstrated based on pre-treatment of DCs with a specific 'cocktail' of select chemokines. Chemokine pre-treatment modulated cytokine production before and after DC maturation [by lipopolysaccharide (LPS)]. After DC maturation, it induced an antigen uptake and processing capacity at levels 36% and 82% higher than in immature DCs, respectively. Such programming proffers a potential new approach to enhance vaccine efficiency. Unfortunately, simply enhancing antigen uptake does not guarantee the desired activation and proliferation of lymphocytes, e.g. CD4(+) T cells. In this study, phenotype changes and antigen presentation capacity of chemokine pre-treated murine bone marrow-derived DCs were examined in long-term co-culture with antigen-specific CD4(+) T cells to quantify how chemokine pre-treatment may impact the adaptive immune response. When a model antigen, ovalbumin (OVA), was added after intentional LPS maturation of chemokine-treated DCs, OVA-biased CD4(+) T-cell proliferation was initiated from ~ 100% more undivided naive T cells as compared to DCs treated only with LPS. Secretion of the cytokines interferon-γ, interleukin-1β, interleukin-2 and interleukin-10 in the CD4(+) T cell : DC co-culture (with or without chemokine pre-treatment) were essentially the same. Chemokine programming of DCs with a 7 : 3 ratio of CCL3 : CCL19 followed by LPS treatment maintained partial immature phenotypes of DCs, as indicated by surface marker (CD80 and CD86) expression over time. Results here and in our companion paper suggest that chemokine programming of DCs may provide a novel immunotherapy strategy to obviate the natural endocytosis limit of DC antigen uptake, thus potentially increasing DC-based vaccine efficiency. © 2012 Blackwell Publishing Ltd.

2011 Annual Progress Report: DOE Hydrogen and Fuel Cells Program (Book)

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

Not Available

In the past year, the DOE Hydrogen and Fuel Cells Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

Highly efficient intracellular transduction in three-dimensional gradients for programming cell fate.

PubMed

Eltaher, Hoda M; Yang, Jing; Shakesheff, Kevin M; Dixon, James E

2016-09-01

Fundamental behaviour such as cell fate, growth and death are mediated through the control of key genetic transcriptional regulators. These regulators are activated or repressed by the integration of multiple signalling molecules in spatio-temporal gradients. Engineering these gradients is complex but considered key in controlling tissue formation in regenerative medicine approaches. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor complexity but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly using GAG-binding domains to promote cell targeting, and cell penetrating peptides (CPPs) to allow cell entry. Herein we demonstrate that GET can be used in a three dimensional (3D) hydrogel matrix to produce gradients of intracellular transduction of mammalian cells. Using a compartmentalised diffusion model with a source-gel-sink (So-G-Si) assembly, we created gradients of reporter proteins (mRFP1-tagged) and a transcription factor (TF, myogenic master regulator MyoD) and showed that GET can be used to deliver molecules into cells spatio-temporally by monitoring intracellular transduction and gene expression programming as a function of location and time. The ability to spatio-temporally control the intracellular delivery of functional proteins will allow the establishment of gradients of cell programming in hydrogels and approaches to direct cellular behaviour for many regenerative medicine applications. Regenerative medicine aims to reform functional biological tissues by controlling cell behaviour. Growth factors (GFs) are soluble cues presented to cells in spatio-temporal gradients and play important roles programming cell fate and gene expression. The efficient transduction of cells by GET (Glycosaminoglycan-enhanced transducing

AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

PubMed

Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

2016-05-27

AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

2015 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

None, None

The 2015 Annual Progress Report summarizes fiscal year 2015 activities and accomplishments by projects funded by the DOE Hydrogen and Fuel Cells Program. It covers the program areas of hydrogen production; hydrogen delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes and standards; systems analysis; and market transformation.

Navy CG(X) Cruiser Program: Background for Congress

DTIC Science & Technology

2010-06-10

PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead, the Chief...procuring CG(X)s was properly aligned with foreign-country ballistic missile development programs. A 2005 defense trade press report, for example, stated

Role of Background in the CERCLA Cleanup Program

EPA Pesticide Factsheets

This document clarifies the U.S. Environmental Protection Agency (EPA) preferred approach for the consideration of background constituent concentrations of hazardous substances, pollutants, and contaminants in certain steps of the remedy selection process

Solid Polymer Electrolyte Fuel Cell Technology Program

NASA Technical Reports Server (NTRS)

1980-01-01

Work is reported on phase 5 of the Solid Polymer Electrolyte (SPE) Fuel Cell Technology Development program. The SPE fuel cell life and performance was established at temperatures, pressures, and current densities significantly higher than those previously demonstrated in sub-scale hardware. Operation of single-cell Buildup No. 1 to establish life capabilities of the full-scale hardware was continued. A multi-cell full-scale unit (Buildup No. 2) was designed, fabricated, and test evaluated laying the groundwork for the construction of a reactor stack. A reactor stack was then designed, fabricated, and successfully test-evaluated to demonstrate the readiness of SPE fuel cell technology for future space applications.

TORO II: A finite element computer program for nonlinear quasi-static problems in electromagnetics: Part 1, Theoretical background

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

Gartling, D.K.

The theoretical and numerical background for the finite element computer program, TORO II, is presented in detail. TORO II is designed for the multi-dimensional analysis of nonlinear, electromagnetic field problems described by the quasi-static form of Maxwell`s equations. A general description of the boundary value problems treated by the program is presented. The finite element formulation and the associated numerical methods used in TORO II are also outlined. Instructions for the use of the code are documented in SAND96-0903; examples of problems analyzed with the code are also provided in the user`s manual. 24 refs., 8 figs.

National fuel cell bus program : proterra fuel cell hybrid bus report, Columbia demonstration.

DOT National Transportation Integrated Search

2011-10-01

This report summarizes the experience and early results from a fuel cell bus demonstration funded by the Federal Transit Administration (FTA) under the National Fuel Cell Bus Program. A team led by the Center for Transportation and the Environment an...

Water Watch Program Overview. Background Information.

ERIC Educational Resources Information Center

Kentucky State Div. of Water, Frankfort. Kentucky Natural Resources and Environmental Protection Cabinet.

Lakes, streams, and wetlands serve many purposes for the people of the state of Kentucky and are necessary and valued elements of its natural resources. The Water Watch program promotes individual responsibility for a common resource, educates people about the use and protection of local water resources, provides recreational opportunities through…

Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

DTIC Science & Technology

2015-10-01

osteoblastic differentiation during aging . Rejuvenation Res 2006;9:10–9. 25] Gao FB, Raff M. Cell size control and a cell-intrinsic maturation program in...self- renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10, 556-569 (2012). 8. Rybak, A.P., Bristow, R.G., & Kapoor, A...established clinical tumor is sustained by subpopulations of self- renewing cancer cells operationally called cancer stem cells (CSC) that can generate

Establishing an autologous versus allogeneic hematopoietic cell transplant program in nations with emerging economies.

PubMed

Chaudhri, Naeem A; Aljurf, Mahmoud; Almohareb, Fahad I; Alzahrani, Hazzaa A; Bashir, Qaiser; Savani, Bipin; Gupta, Vikas; Hashmi, Shahrukh K

2017-12-01

More than 70,000 hematopoietic cell transplants are currently performed each year, and these continue to increase every year. However, there is a significant variation in the number of absolute transplants and transplant rates between centers, countries, and global regions. The prospect for emerging countries to develop a hematopoietic cell transplantation (HCT) program, as well as to decide on whether autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) should be established to start with, relies heavily on factors that can explain differences between these two procedures. Major factors that will influence a decision about establishing the type of HCT program are macroeconomic factors such as organization of the healthcare network, available resources and infrastructure. Prevalence of specific diseases in the region as well genetic background of donors and recipients will also influence the mandate or priority of the HCT in the national healthcare plan to explain some of the country-specific differences. Furthermore, microeconomic factors play a role, such as center-specific experience in treating various disorders requiring hematopoietic stem cell transplantation, along with accreditation status and patient volume. The objective of the transplant procedure was to improve the survival and quality of life of patients. The regional difference that one notices in emerging countries about the higher number of allo-HCT compared with auto-HCT procedures performed is primarily based on suboptimal healthcare network in treating various malignant disorders that are the primary indication for auto-stem cell transplantation. In this context, nonmalignant disorders such as bone marrow failure syndromes, inherited genetic disorders and hemoglobinopathies have become the major indication for stem cell transplantation. Better understanding of these factors will assist in establishing new transplant centers in the emerging countries to achieve their specific objectives and

Lithium-doped solar cell pilot line fabrication and test programs

NASA Technical Reports Server (NTRS)

Berman, P. A.; Yasui, R. K.

1974-01-01

An investigation was conducted to determine the technology readiness of lithium-doped silicon solar cells with respect to use in space programs. A pilot line fabrication program was established, in which the pilot line cells were evaluated after being exposed to environments ordinarily imposed on nonlithium-doped silicon solar cells. Results indicate that further process improvements are required, particularly with respect to the P/N junction diffusion and the electrical contacting technique (including solder coating). It is concluded that lithium-doped cells can be fabricated to exhibit (1) high efficiencies, (2) uniform cell-to-cell recovery characteristics after exposure to 1-MeV electrons; and (3) good stability in most environments investigated (the only exception being the thermal shock environment).

PKCepsilon overexpression, irrespective of genetic background, sensitizes skin to UVR-induced development of squamous-cell carcinomas.

PubMed

Sand, Jordan M; Aziz, Moammir H; Dreckschmidt, Nancy E; Havighurst, Thomas C; Kim, KyungMann; Oberley, Terry D; Verma, Ajit K

2010-01-01

Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKCepsilon) transgenic mice on FVB/N background, which overexpress PKCepsilon protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKCepsilon and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKCepsilon FVB/N transgenic mice with SKH-1 hairless mice to generate PKCepsilon-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCepsilon SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1-2 KJ m(-2)) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKCepsilon overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKCepsilon level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis.

2016 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

None, None

The 2016 Annual Progress Report summarizes fiscal year 2016 activities and accomplishments by projects funded by the DOE Hydrogen and Fuel Cells Program. It covers the program areas of hydrogen production; hydrogen delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes and standards; systems analysis; market transformation; and Small Business Innovation Research projects.

Evaluation of a neonatal screening program for sickle-cell disease.

PubMed

Eller, Rodrigo; da Silva, Denise Bousfield

2016-01-01

Evaluate the Neonatal Screening Program of the Health Secretariat of the State of Santa Catarina for sickle-cell disease, from January 2003 to December 2012, regarding program coverage and disease frequency. Descriptive, observational, cross-sectional study with retrospective data collection. The variables analyzed were: number of live births in the State of Santa Catarina; number of screened children; number of children diagnosed with sickle-cell trait and sickle-cell disease; type of sickle-cell disease diagnosed; age at the time of sample collection, ethnicity/skin color, gender, and origin of children with sickle-cell disease. Descriptive measures and frequency tables were used for data analysis. During the study period, there were 848,833 live births and 730,412 samples were screened by the program, resulting in a coverage of 86.0%. There were 6173 samples positive for sickle-cell trait and 39 for sickle-cell disease. Among children with sickle-cell disease, the median age at the time of sample collection was 6 days. Regarding the ethnicity/skin color, 25 (64.1%) children were white, seven were black, and seven others were not specified. The Midwest and the Highland (Planalto Serrano) of Santa Catarina were the regions with the highest incidence of sickle-cell disease. Coverage by the Neonatal Screening Program of Santa Catarina is good, but did not demonstrate an improvement trend over the years. The frequency of sickle-cell disease is low and lower than in the North, Northeast, and Midwest regions. The median age in days at the time of collection is older than the age recommended by the Ministry of Health. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Granularity of the Diffuse Background Observed

NASA Technical Reports Server (NTRS)

Gruber, D. E.; MacDonald, D.; Rothschild, R. E.; Boldt, E.; Mushotzky, R. F.; Fabian, A. C.

1995-01-01

First results are reported from a program for measuring the field-to-field fluctuation level of the cosmic diffuse background by using differences between the two background positions of each deep exposure with the High Energy X-ray Timing Experiment (HEXTE) instrument on the Remote X Ray Timing Explorer (RXTE). With 8 million live seconds accumulated to date a fluctuation level on the 15-25 keV band is observed which is consistent with extrapolations from the High Energy Astrophysical Observatory-1 (HEAO-1) measurements. Positive results are expected eventually at higher energies. Models of (active galactic nuclei) AGN origin will eventually be constrained by this program.

Long-term treatment of anterior pituitary cells with nitric oxide induces programmed cell death.

PubMed

Velardez, Miguel Omar; Poliandri, Ariel Hernán; Cabilla, Jimena Paula; Bodo, Cristian Carlos Armando; Machiavelli, Leticia Inés; Duvilanski, Beatriz Haydeé

2004-04-01

Nitric oxide (NO) plays a complex role in modulating programmed cell death. It can either protect the cell from apoptotic death or mediate apoptosis, depending on its concentration and the cell type and/or status. In this study, we demonstrate that long-term exposition to NO induces cell death of anterior pituitary cells from Wistar female rats. DETA NONOate (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, 1 mm], a NO donor that releases NO for an extended period of time, decreased cellular viability and prolactin release from primary cultures of anterior pituitary cells. Morphological studies showed an increase in the number of cells with chromatin condensation and nuclear fragmentation at 24 and 48 h after DETA/NO exposure. DNA internucleosomal fragmentation was also observed at the same time. Reversibility of the NO effect on cellular viability and prolactin release was observed only when the cells were incubated with DETA/NO for less than 6 h. Most apoptotic cells were immunopositive for prolactin, suggesting a high susceptibility of lactotrophs to the effect of NO. The cytotoxic effect of NO is dependent of caspase-9 and caspase-3, but seems to be independent of oxidative stress or nitrosative stress. Our results show that the exposition of anterior pituitary cells to NO for long periods induces programmed cell death of anterior pituitary cells.

Afterschool Alliance Backgrounder: Formal Evaluations of Afterschool Programs.

ERIC Educational Resources Information Center

Afterschool Alliance, Washington, DC.

Noting that various types of evaluations of after-school programming conducted over the last several years have provided useful information to providers and to policymakers, this report summarizes the lessons learned from independent evaluations of after-school programs. The following overall findings are supported with a delineation of findings…

Solid Polymer Electrolyte (SPE) fuel cell technology program

NASA Technical Reports Server (NTRS)

1979-01-01

The overall objectives of the Phase IV Solid Polymer Electrolyte Fuel Cell Technology Program were to: (1) establish fuel cell life and performance at temperatures, pressures and current densities significantly higher than those previously demonstrated; (2) provide the ground work for a space energy storage system based on the solid polymer electrolyte technology (i.e., regenerative H2/O2 fuel cell); (3) design, fabricate and test evaluate a full-scale single cell unit. During this phase, significant progress was made toward the accomplishment of these objectives.

U.S. Army PEM fuel cell programs

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

Patil, A.S.; Jacobs, R.

The United States Army has identified the need for lightweight power sources to provide the individual soldier with continuous power for extended periods without resupply. Due to the high cost of primary batteries and the high weight of rechargeable batteries, fuel cell technology is being developed to provide a power source for the individual soldier, sensors, communications equipment and other various applications in the Army. Current programs are in the tech base area and will demonstrate Proton Exchange Membrane (PEM) Fuel Cell Power Sources with low weight and high energy densities. Fuel Cell Power Sources underwent user evaluations in 1996more » that showed a power source weight reduction of 75%. The quiet operation along with the ability to refuel much like an engine was well accepted by the user and numerous applications were investigated. These programs are now aimed at further weight reduction for applications that are weight critical; system integration that will demonstrate a viable military power source; refining the user requirements; and planning for a transition to engineering development.« less

Programmed cell senescence during mammalian embryonic development.

PubMed

Muñoz-Espín, Daniel; Cañamero, Marta; Maraver, Antonio; Gómez-López, Gonzalo; Contreras, Julio; Murillo-Cuesta, Silvia; Rodríguez-Baeza, Alfonso; Varela-Nieto, Isabel; Ruberte, Jesús; Collado, Manuel; Serrano, Manuel

2013-11-21

Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is strictly dependent on p21, but independent of DNA damage, p53, or other cell-cycle inhibitors, and it is regulated by the TGF-β/SMAD and PI3K/FOXO pathways. Developmentally programmed senescence is followed by macrophage infiltration, clearance of senescent cells, and tissue remodeling. Loss of senescence due to the absence of p21 is partially compensated by apoptosis but still results in detectable developmental abnormalities. Importantly, the mesonephros and endolymphatic sac of human embryos also show evidence of senescence. We conclude that the role of developmentally programmed senescence is to promote tissue remodeling and propose that this is the evolutionary origin of damage-induced senescence. Copyright © 2013 Elsevier Inc. All rights reserved.

14 CFR 1203.200 - Background and discussion.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 1203.200 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION INFORMATION SECURITY PROGRAM NASA Information Security Program § 1203.200 Background and discussion. (a) In establishing a... public inspection of that information that is classified to protect the national security. (b) In...

14 CFR 1203.200 - Background and discussion.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 1203.200 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION INFORMATION SECURITY PROGRAM NASA Information Security Program § 1203.200 Background and discussion. (a) In establishing a... public inspection of that information that is classified to protect the national security. (b) In...

Profile of graduates of Israeli medical schools in 1981--2000: educational background, demography and evaluation of medical education programs.

PubMed

Bitterman, Noemi; Shalev, Ilana

2005-05-01

In light of changes in the medical profession, the different requirements placed on physicians and the evolving needs of the healthcare system, the need arose to examine the medical education curriculum in Israel. This survey, conducted by the Samuel Neaman Institute for Science and Technology, summarizes 20 years of medical education in Israel's four medical schools, as the first stage in mapping the existing state of medical education in Israel and providing a basis for decision-making on future medical education programs. To characterize the academic background of graduates, evaluate their attitudes towards current and alternative medical education programs, and examine subgroups among graduates according to gender, medical school, high school education, etc. The survey included graduates from all four Israeli medical schools who graduated between the years 1981 and 2000 in a sample of 1:3. A questionnaire and stamped return envelope were sent to every third graduate; the questionnaire included open and quantitative questions graded on a scale of 1 to 5. The data were processed for the entire graduate population and further analyzed according to subgroups such as medical schools, gender, high school education, etc. The response rate was 41.3%. The survey provided a demographic profile of graduates over a 20 year period, their previous educational and academic background, additional academic degrees achieved, satisfaction, and suggestions for future medical education programs. The profile of the medical graduates in Israel is mostly homogenous in terms of demographics, with small differences among the four medical schools. In line with recommendations of the graduates, and as an expression of the changing requirements in the healthcare system and the medical profession, the medical schools should consider alternative medical education programs such as a bachelor's degree in life sciences followed by MD studies, or education programs that combine medicine with

Molecular mechanisms of programmed cell death-1 dependent T cell suppression: relevance for immunotherapy

PubMed Central

Zuazo, Miren; Gato-Cañas, Maria; Llorente, Noelia; Ibañez-Vea, María; Arasanz, Hugo

2017-01-01

Programmed cell death-1 (PD1) has become a significant target for cancer immunotherapy. PD1 and its receptor programmed cell death 1 ligand 1 (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. However, cancer cells take advantage of these immunosuppressive regulatory mechanisms to escape T and B cell-mediated immunity. PD1 engagement on T cells by PDL1 on the surface of cancer cells dramatically interferes with T cell activation and the acquisition of effector capacities. Interestingly, PD1-targeted therapies have demonstrated to be highly effective in rescuing T cell anti-tumor effector functions. Amongst these the use of anti-PD1/PDL1 monoclonal antibodies are particularly efficacious in human therapies. Furthermore, clinical findings with PD1/PDL1 blockers over several cancer types demonstrate clinical benefit. Despite the successful results, the molecular mechanisms by which PD1-targeted therapies rescue T cell functions still remain elusive. Therefore, it is a key issue to uncover the molecular pathways by which these therapies exert its function in T cells. A profound knowledge of PDL1/PD1 mechanisms will surely uncover a new array of targets susceptible of therapeutic intervention. Here, we provide an overview of the molecular events underlying PD1-dependent T cell suppression in cancer. PMID:29114543

Ni-H2 cell characterization for INTELSAT programs

NASA Technical Reports Server (NTRS)

Dunnet, Andrew F.; Earl, Martin W.

1994-01-01

Various Ni/H2 cell designs manufactured for INTELSAT Programs during the past decade have been characterized electrically as a function of temperature. The resulting data for these INTELSAT V, VI, VII and VIIA cells are assembled in a manner which allows ready comparison of performance. Also included is a detailed description of each design.

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity

PubMed Central

Mazzoni, Esteban O; Mahony, Shaun; Closser, Michael; Morrison, Carolyn A; Nedelec, Stephane; Williams, Damian J; An, Disi; Gifford, David K; Wichterle, Hynek

2013-01-01

Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation–sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type–specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types. PMID:23872598

The Influence of Parents' Backgrounds, Beliefs about English Learning, and a Dialogic Reading Program on Thai Kindergarteners' English Lexical Development

ERIC Educational Resources Information Center

Petchprasert, Anongnad

2014-01-01

This study investigated parents' backgrounds and their beliefs about English language learning, and compared the receptive English vocabulary development of three to six year-old-Thai children before and after participating in a parent-child reading program with the dialogic reading (DR) method. Fifty-four single parents of 54 children voluntarily…

Legal, Ethical, Social and Economic Issues in Sickle Cell Program

ERIC Educational Resources Information Center

Bowman, James E.

1973-01-01

Urges that mandatory sickle cell screening laws be repealed, and that all screening programs be voluntary; bogus sickle cell organizations are a major crisis in black communities and must be eliminated; research and education in sickle cell disease is badly needed. (Author/JM)

NASA's PEM Fuel Cell Power Plant Development Program for Space Applications

NASA Technical Reports Server (NTRS)

Hoberecht, Mark A.

2008-01-01

A three-center NASA team led by the Glenn Research Center in Cleveland, Ohio is completing a five-year PEM fuel cell power plant development program for future space applications. The focus of the program has been to adapt commercial PEM fuel cell technology for space applications by addressing the key mission requirements of using pure oxygen as an oxidant and operating in a multi-gravity environment. Competing vendors developed breadboard units in the 1 to 5 kW power range during the first phase of the program, and a single vendor developed a nominal 10-kW engineering model power pant during the second phase of the program. Successful performance and environmental tests conducted by NASA established confidence that PEM fuel cell technology will be ready to meet the electrical power needs of future space missions.

Modeling Lost-Particle Backgrounds in PEP-II Using LPTURTLE

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

Fieguth, T.; /SLAC; Barlow, R.

2005-05-17

Background studies during the design, construction, commissioning, operation and improvement of BaBar and PEP-II have been greatly influenced by results from a program referred to as LPTURTLE (Lost Particle TURTLE) which was originally conceived for the purpose of studying gas background for SLC. This venerable program is still in use today. We describe its use, capabilities and improvements and refer to current results now being applied to BaBar.

Effect of whole-body irradiation of mice on the number of background plaque-forming cells

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

Anderson, R.E.; Lefkovits, I.; Soeederberg, A.

1983-08-01

Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found inmore » irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.« less

40 CFR 105.1 - Background.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Background. 105.1 Section 105.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER... the preceding year demonstrated an outstanding technological achievement or an innovative process...

40 CFR 105.1 - Background.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Background. 105.1 Section 105.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER... the preceding year demonstrated an outstanding technological achievement or an innovative process...

40 CFR 105.1 - Background.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Background. 105.1 Section 105.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER... the preceding year demonstrated an outstanding technological achievement or an innovative process...

40 CFR 105.1 - Background.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Background. 105.1 Section 105.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER... the preceding year demonstrated an outstanding technological achievement or an innovative process...

40 CFR 105.1 - Background.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Background. 105.1 Section 105.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS RECOGNITION AWARDS UNDER... the preceding year demonstrated an outstanding technological achievement or an innovative process...

Navy CG(X) Cruiser Program: Background for Congress

DTIC Science & Technology

2010-04-08

PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...Inside the Navy, October 27, 2008. Another press report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures...have changed.37 A related question was whether the schedule for procuring CG(X)s was properly aligned with foreign-country ballistic missile

Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells

PubMed Central

Somervaille, Tim C. P.; Matheny, Christina J.; Spencer, Gary J.; Iwasaki, Masayuki; Rinn, John L.; Witten, Daniela M.; Chang, Howard Y.; Shurtleff, Sheila A.; Downing, James R.; Cleary, Michael L.

2009-01-01

Summary The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. PMID:19200802

Necroptosis: an alternative cell death program defending against cancer

PubMed Central

Chen, Dongshi; Yu, Jian; Zhang, Lin

2016-01-01

One of the hallmarks of cancer is resistance to programmed cell death, which maintains the survival of cells en route to oncogenic transformation and underlies therapeutic resistance. Recent studies demonstrate that programmed cell death is not confined to caspase-dependent apoptosis, but includes necroptosis, a form of necrotic death governed by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as a critical cell-killing mechanism in response to severe stress and blocked apoptosis, and can be induced by inflammatory cytokines or chemotherapeutic drugs. Genetic or epigenetic alterations of necroptosis regulators such as RIP3 and cylindromatosis (CYLD), are frequently found in human tumors. Unlike apoptosis, necroptosis elicits a more robust immune response that may function as a defensive mechanism by eliminating tumor-causing mutations and viruses. Furthermore, several classes of anticancer agents currently under clinical development, such as SMAC and BH3 mimetics, can promote necroptosis in addition to apoptosis. A more complete understanding of the interplay among necroptosis, apoptosis, and other cell death modalities is critical for developing new therapeutic strategies to enhance killing of tumor cells. PMID:26968619

Necroptosis: an alternative cell death program defending against cancer.

PubMed

Chen, Dongshi; Yu, Jian; Zhang, Lin

2016-04-01

One of the hallmarks of cancer is resistance to programmed cell death, which maintains the survival of cells en route to oncogenic transformation and underlies therapeutic resistance. Recent studies demonstrate that programmed cell death is not confined to caspase-dependent apoptosis, but includes necroptosis, a form of necrotic death governed by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL) protein. Necroptosis serves as a critical cell-killing mechanism in response to severe stress and blocked apoptosis, and can be induced by inflammatory cytokines or chemotherapeutic drugs. Genetic or epigenetic alterations of necroptosis regulators such as RIP3 and cylindromatosis (CYLD), are frequently found in human tumors. Unlike apoptosis, necroptosis elicits a more robust immune response that may function as a defensive mechanism by eliminating tumor-causing mutations and viruses. Furthermore, several classes of anticancer agents currently under clinical development, such as SMAC and BH3 mimetics, can promote necroptosis in addition to apoptosis. A more complete understanding of the interplay among necroptosis, apoptosis, and other cell death modalities is critical for developing new therapeutic strategies to enhance killing of tumor cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Fast and background-free three-dimensional (3D) live-cell imaging with lanthanide-doped upconverting nanoparticles.

PubMed

Jo, Hong Li; Song, Yo Han; Park, Jinho; Jo, Eun-Jung; Goh, Yeongchang; Shin, Kyujin; Kim, Min-Gon; Lee, Kang Taek

2015-12-14

We report on the development of a three-dimensional (3D) live-cell imaging technique with high spatiotemporal resolution using lanthanide-doped upconverting nanoparticles (UCNPs). It employs the sectioning capability of confocal microscopy except that the two-dimensional (2D) section images are acquired by wide-field epi-fluorescence microscopy. Although epi-fluorescence images are contaminated with the out-of-focus background in general, the near-infrared (NIR) excitation used for the excitation of UCNPs does not generate any autofluorescence, which helps to lower the background. Moreover, the image blurring due to defocusing was naturally eliminated in the image reconstruction process. The 3D images were used to investigate the cellular dynamics such as nuclear uptake and single-particle tracking that require 3D description.

On-site fuel cell field test support program

NASA Astrophysics Data System (ADS)

Staniunas, J. W.; Merten, G. P.

1982-01-01

In order to assess the impact of grid connection on the potential market for fuel cell service, applications studies were conducted to identify the fuel cell operating modes and corresponding fuel cell sizing criteria which offer the most potential for initial commercial service. The market for grid-connected fuel cell service was quantified using United's market analysis program and computerized building data base. Electric and gas consumption data for 268 buildings was added to our surveyed building data file, bringing the total to 407 buildings. These buildings were analyzed for grid-isolated and grid-connected fuel cell service. The results of the analyses indicated that the nursing home, restaurant and health club building sectors offer significant potential for fuel cell service.

The 1975 Every Student Survey: The Background of Students in Special Education and New Canadian Programs. Research Report No. 141.

ERIC Educational Resources Information Center

Gershman, Janis

Presented is the final report based on the 1975 Every Student Survey describing the demographic characteristics of about 13,000 students in the Toronto school system who are enrolled in the New Canadian and each of the 15 Special Education programs. The report describes the socio-economic background, mother tongue, country of birth, and family…

Navy CG(X) Cruiser Program: Background for Congress

DTIC Science & Technology

2010-09-28

NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead...number of CG(X)s could have changed.38 A related question was whether the schedule for procuring CG(X)s was properly aligned with foreign-country

Navy CG(X) Cruiser Program: Background for Congress

DTIC Science & Technology

2010-02-26

5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead...CG(X)s could change.40 A related question was whether the schedule for procuring CG(X)s was properly aligned with foreign-country ballistic missile

Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells.

PubMed

Li, Deguan; Chen, Renxiang; Wang, Yi-Wen; Fornace, Albert J; Li, Heng-Hong

2018-05-01

In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors. Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ranging from one to four weeks in mice receiving a single fraction of 1 or 4 Gy of γ-ray. T cell activation associated metabolic changes were assessed. Our results showed that prior irradiation resulted in significant elevated expression of programmed cell death protein 1 (PD-1) in both CD4+ and CD8+ populations, at all three post-radiation time points. T cells with elevated PD-1 mostly were either central memory or naïve cells. In addition, the feedback induction of PD-1 expression in activated T cells declined after radiation. Taken together, the elevated PD-1 level observed at weeks after radiation exposure is connected to T cell dysfunction. Recent preclinical and clinical studies have showed that a combination of radiotherapy and T cell checkpoint blockade immunotherapy including targeting the programmed death-ligand 1 (PD-L1)/PD-1 axis may potentiate the antitumor response. Understanding the dynamic changes in PD-1 levels in T cells after radiation should help in the development of a more effective therapeutic strategy.

Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program

PubMed Central

Hamey, Fiona K.; Errami, Youssef

2017-01-01

Differentiation of lineage-committed cells from multipotent progenitors requires the establishment of accessible chromatin at lineage-specific transcriptional enhancers and promoters, which is mediated by pioneer transcription factors that recruit activating chromatin remodeling complexes. Here we show that the Mbd3/nucleosome remodeling and deacetylation (NuRD) chromatin remodeling complex opposes this transcriptional pioneering during B cell programming of multipotent lymphoid progenitors by restricting chromatin accessibility at B cell enhancers and promoters. Mbd3/NuRD-deficient lymphoid progenitors therefore prematurely activate a B cell transcriptional program and are biased toward overproduction of pro–B cells at the expense of T cell progenitors. The striking reduction in early thymic T cell progenitors results in compensatory hyperproliferation of immature thymocytes and development of T cell lymphoma. Our results reveal that Mbd3/NuRD can regulate multilineage differentiation by constraining the activation of dormant lineage-specific enhancers and promoters. In this way, Mbd3/NuRD protects the multipotency of lymphoid progenitors, preventing B cell–programming transcription factors from prematurely enacting lineage commitment. Mbd3/NuRD therefore controls the fate of lymphoid progenitors, ensuring appropriate production of lineage-committed progeny and suppressing tumor formation. PMID:28899870

An Education Program to Increase Teacher Knowledge about Sickle Cell Disease.

ERIC Educational Resources Information Center

King, Allison A.; Tang, Sujie; Ferguson, Kim L.; DeBaun, Michael R.

2005-01-01

This program evaluated the effectiveness of a sickle cell disease (SCD) education program for teachers of students with SCD in their classroom. Teachers with students in a remediation program for students participated in an educational program consisting of four domains: Inheritance and Prevalence, Common Complications, Strokes, and Individual…

Educational Choice. A Background Paper.

ERIC Educational Resources Information Center

Quality Education for Minorities Network, Washington, DC.

This paper addresses school choice, one proposal to address parental involvement concerns, focusing on historical background, definitions, rationale for advocating choice, implementation strategies, and implications for minorities and low-income families. In the past, transfer payment programs such as tuition tax credits and vouchers were…

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway: A New Target for Sepsis.

PubMed

Liu, Qiang; Li, Chun-Sheng

2017-04-20

Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment. Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database. English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated. Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells. The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

Integration of T Cell Receptor, Notch and Cytokine Signals Programs in Mouse γδ T Cell Effector Differentiation.

PubMed

Zarin, Payam; In, Tracy S H; Chen, Edward L Y; Singh, Jastaranpreet; Wong, Gladys W; Mohtashami, Mahmood; Wiest, David L; Anderson, Michele K; Zúñiga-Pflücker, Juan Carlos

2018-05-13

γδ T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2 -/- T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNγ versus IL-17 producing γδ T cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL-1β, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNγ and IL-17 producing γδ T-cell subsets. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Below-Background Ionizing Radiation as an Environmental Cue for Bacteria

DOE PAGES

Castillo, Hugo; Smith, Geoffrey B.

2017-02-14

All organisms on earth grow under the influence of a natural and relatively constant dose of ionizing radiation referred to as background radiation, and so cells have different mechanisms to prevent the accumulation of damage caused by its different components. However, current knowledge of the deleterious effects of radiation on cells is based on the exposure to acute and high or to chronic, above background doses of radiation and therefore is not appropriate to explain the cellular and biochemical mechanisms that cells employ to sense and respond to chronic below-background levels. Studies at below-background radiation doses can provide insight intomore » the biological role of radiation, as suggested by several examples of what appears to be a stress response in cells grown at doses that range from 10 to 79 times lower than background. Here, we discuss some of the technical constraints to shield cells from radiation to below-background levels, as well as different approaches used to detect and measure responses to such unusual environmental conditions. Then, we present data from Shewanella oneidensis and Deinococcus radiodurans experiments that show how two taxonomically distant bacterial species sense and respond to unnaturally low levels of radiation. Finally, in brief, we grew S. oneidensis and D. radiodurans in liquid culture at dose rates of 72.05 (control) and 0.91 (treatment) nGy hr -1 (including radon) for up to 72 h and measured cell density and the expression of stress-related genes. Our results suggest that a stress response is triggered in the absence of normal levels of radiation.« less

Below-Background Ionizing Radiation as an Environmental Cue for Bacteria

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

Castillo, Hugo; Smith, Geoffrey B.

All organisms on earth grow under the influence of a natural and relatively constant dose of ionizing radiation referred to as background radiation, and so cells have different mechanisms to prevent the accumulation of damage caused by its different components. However, current knowledge of the deleterious effects of radiation on cells is based on the exposure to acute and high or to chronic, above background doses of radiation and therefore is not appropriate to explain the cellular and biochemical mechanisms that cells employ to sense and respond to chronic below-background levels. Studies at below-background radiation doses can provide insight intomore » the biological role of radiation, as suggested by several examples of what appears to be a stress response in cells grown at doses that range from 10 to 79 times lower than background. Here, we discuss some of the technical constraints to shield cells from radiation to below-background levels, as well as different approaches used to detect and measure responses to such unusual environmental conditions. Then, we present data from Shewanella oneidensis and Deinococcus radiodurans experiments that show how two taxonomically distant bacterial species sense and respond to unnaturally low levels of radiation. Finally, in brief, we grew S. oneidensis and D. radiodurans in liquid culture at dose rates of 72.05 (control) and 0.91 (treatment) nGy hr -1 (including radon) for up to 72 h and measured cell density and the expression of stress-related genes. Our results suggest that a stress response is triggered in the absence of normal levels of radiation.« less

A mentor training program improves mentoring competency for researchers working with early-career investigators from underrepresented backgrounds.

PubMed

Johnson, Mallory O; Gandhi, Monica

2015-08-01

Mentoring is increasingly recognized as a critical element in supporting successful careers in academic research in medicine and related disciplines, particularly for trainees and early career investigators from underrepresented backgrounds. Mentoring is often executed ad hoc; there are limited programs to train faculty to become more effective mentors, and the few that exist have a dearth of empirical support of their impact. In 2013, we recruited 34 faculty from across the US engaged in HIV-related clinical research to participate in a 2-day Mentoring the Mentors workshop. The workshop included didactic and interactive content focused on a range of topics, such as mentor-mentee communication, leadership styles, emotional intelligence, understanding the impact of diversity (unconscious bias, microaggressions, discrimination, tokenism) for mentees, and specific tools and techniques for effective mentoring. Pre- and post-workshop online evaluations documented high rates of satisfaction with the program and statistically significant improvements in self-appraised mentoring skills (e.g. addressing diversity in mentoring, communication with mentees, aligning mentor-mentee expectations), as assessed via a validated mentoring competency tool. This is the first mentoring training program focused on enhancing mentors' abilities to nurture investigators of diversity, filling an important gap, and evaluation results offer support for its effectiveness. Results suggest a need for refinement and expansion of the program and for more comprehensive, long-term evaluation of distal mentoring outcomes for those who participate in the program.

2016 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Satyapal, Sunita

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

2012 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Not Available

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

2015 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

Popovich, Neil

In the past year, the DOE Hydrogen Program (the Program) made substantial progress toward its goals and objectives. The Program has conducted comprehensive and focused efforts to enable the widespread commercialization of hydrogen and fuel cell technologies in diverse sectors of the economy. With emphasis on applications that will effectively strengthen our nation's energy security and improve our stewardship of the environment, the Program engages in research, development, and demonstration of critical improvements in the technologies. Highlights of the Program's accomplishments can be found in the sub-program chapters of this report.

Predicting performance using background characteristics of international medical graduates in an inner-city university-affiliated Internal Medicine residency training program

PubMed Central

Kanna, Balavenkatesh; Gu, Ying; Akhuetie, Jane; Dimitrov, Vihren

2009-01-01

Background IMGs constitute about a third of the United States (US) internal medicine graduates. US residency training programs face challenges in selection of IMGs with varied background features. However data on this topic is limited. We analyzed whether any pre-selection characteristics of IMG residents in our internal medicine program are associated with selected outcomes, namely competency based evaluation, examination performance and success in acquiring fellowship positions after graduation. Methods We conducted a retrospective study of 51 IMGs at our ACGME accredited teaching institution between 2004 and 2007. Background resident features namely age, gender, self-reported ethnicity, time between medical school graduation to residency (pre-hire time), USMLE step I & II clinical skills scores, pre-GME clinical experience, US externship and interest in pursuing fellowship after graduation expressed in their personal statements were noted. Data on competency-based evaluations, in-service exam scores, research presentation and publications, fellowship pursuance were collected. There were no fellowships offered in our hospital in this study period. Background features were compared between resident groups according to following outcomes: (a) annual aggregate graduate PGY-level specific competency-based evaluation (CBE) score above versus below the median score within our program (scoring scale of 1 – 10), (b) US graduate PGY-level specific resident in-training exam (ITE) score higher versus lower than the median score, and (c) those who succeeded to secure a fellowship within the study period. Using appropriate statistical tests & adjusted regression analysis, odds ratio with 95% confidence intervals were calculated. Results 94% of the study sample were IMGs; median age was 35 years (Inter-Quartile range 25th – 75th percentile (IQR): 33–37 years); 43% women and 59% were Asian physicians. The median pre-hire time was 5 years (IQR: 4–7 years) and USMLE step

Arabidopsis ACCELERATED CELL DEATH2 Modulates Programmed Cell DeathW⃞

PubMed Central

Yao, Nan; Greenberg, Jean T.

2006-01-01

The Arabidopsis thaliana chloroplast protein ACCELERATED CELL DEATH2 (ACD2) modulates the amount of programmed cell death (PCD) triggered by Pseudomonas syringae and protoporphyrin IX (PPIX) treatment. In vitro, ACD2 can reduce red chlorophyll catabolite, a chlorophyll derivative. We find that ACD2 shields root protoplasts that lack chlorophyll from light- and PPIX-induced PCD. Thus, chlorophyll catabolism is not obligatory for ACD2 anti-PCD function. Upon P. syringae infection, ACD2 levels and localization change in cells undergoing PCD and in their close neighbors. Thus, ACD2 shifts from being largely in chloroplasts to partitioning to chloroplasts, mitochondria, and, to a small extent, cytosol. ACD2 protects cells from PCD that requires the early mitochondrial oxidative burst. Later, the chloroplasts of dying cells generate NO, which only slightly affects cell viability. Finally, the mitochondria in dying cells have dramatically altered movements and cellular distribution. Overproduction of both ACD2 (localized to mitochondria and chloroplasts) and ascorbate peroxidase (localized to chloroplasts) greatly reduces P. syringae–induced PCD, suggesting a pro-PCD role for mitochondrial and chloroplast events. During infection, ACD2 may bind to and/or reduce PCD-inducing porphyrin-related molecules in mitochondria and possibly chloroplasts that generate reactive oxygen species, cause altered organelle behavior, and activate a cascade of PCD-inducing events. PMID:16387834

Stress Management in Cyst-Forming Free-Living Protists: Programmed Cell Death and/or Encystment

PubMed Central

Khan, Naveed Ahmed; Iqbal, Junaid

2015-01-01

In the face of harsh conditions and given a choice, a cell may (i) undergo programmed cell death, (ii) transform into a cancer cell, or (iii) enclose itself into a cyst form. In metazoans, the available evidence suggests that cellular machinery exists only to execute or avoid programmed cell death, while the ability to form a cyst was either lost or never developed. For cyst-forming free-living protists, here we pose the question whether the ability to encyst was gained at the expense of the programmed cell death or both functions coexist to counter unfavorable environmental conditions with mutually exclusive phenotypes. PMID:25648302

Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

PubMed

Hoffmann, Else Kay

2011-01-01

This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death

PubMed Central

Kuriakose, Teneema; Malireddi, R.K. Subbarao; Mishra, Ashutosh

2017-01-01

Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death. PMID:28634194

Megasporogenesis and programmed cell death in Tillandsia (Bromeliaceae).

PubMed

Papini, Alessio; Mosti, Stefano; Milocani, Eva; Tani, Gabriele; Di Falco, Pietro; Brighigna, Luigi

2011-10-01

The degeneration of three of four meiotic products is a very common process in the female gender of oogamous eukaryotes. In Tillandsia (and many other angiosperms), the surviving megaspore has a callose-free wall in chalazal position while the other three megaspores are completely embedded in callose. Therefore, nutrients and signals can reach more easily the functional megaspore from the nucellus through the chalazal pole with respect to the other megaspores. The abortion of three of four megaspores was already recognized as the result of a programmed cell death (PCD) process. We investigated the process to understand the modality of this specific type of PCD and its relationship to the asymmetric callose deposition around the tetrad. The decision on which of the four megaspores will be the supernumerary megaspores in angiosperms, and hence destined to undergo programmed cell death, appears to be linked to the callose layer deposition around the tetrad. During supernumerary megaspores degeneration, events leading to the deletion of the cells do not appear to belong to a single type of cell death. The first morphological signs are typical of autophagy, including the formation of autophagosomes. The TUNEL positivity and a change in morphology of mitochondria and chloroplasts indicate the passage to an apoptotic-like PCD phase, while the cellular remnants undergo a final process resembling at least partially (ER swelling) necrotic morphological syndromes, eventually leading to a mainly lipidic cell corpse still separated from the functional megaspore by a callose layer.

Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death

PubMed Central

1996-01-01

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point. PMID:8642331

Notification: Audit of EPA's Processes for Managing Background Investigations of Privileged Users and Taking Action to Remediate Weaknesses in Agency's Information Security Program

EPA Pesticide Factsheets

Project #OA-FY17-0139, Feb 15, 2017.The EPA OIG plans to begin preliminary research on an audit of EPA's processes for managing background investigations of privileged users and taking action to remediate weaknesses in agency's info security program.

Anti-CHMP5 single chain variable fragment antibody retrovirus infection induces programmed cell death of AML leukemic cells in vitro.

PubMed

Wang, Hai-rong; Xiao, Zhen-yu; Chen, Miao; Wang, Fei-long; Liu, Jia; Zhong, Hua; Zhong, Ji-hua; Ou-Yang, Ren-rong; Shen, Yan-lin; Pan, Shu-ming

2012-06-01

Over-expressed CHMP5 was found to act as oncogene that probably participated in leukemogenesis. In this study, we constructed the CHMP5 single chain variable fragment antibody (CHMP5-scFv) retrovirus and studied the changes of programmed cell death (PCD) of AML leukemic cells after infection by the retrovirus. The anti-CHMP5 KC14 hybridoma cell line was constructed to generate monoclonal antibody of CHMP5. The protein expression of CHMP5 was studied using immunofluorescence analysis. pMIG-CHMP5 scFv antibody expressible retroviral vector was constructed to prepare CHMP5-scFv retrovirus. AML leukemic U937 cells were infected with the retrovirus, and programmed cell death was studied using confocal microscope, FCM and Western blot. We obtained a monoclonal antibody of CHMP5, and found the expression of CHMP5 was up-regulated in the leukemic cells. After U937 cells were infected with CHMP5-scFv retrovirus, CHMP5 protein was neutralized. Moreover, the infection resulted in a significant increase in apoptosis and necrosis of U937 cells. In U937 cells infected with CHMP5-scFv retrovirus, apoptosis-inducing factor (AIF)-mediated caspase-independent necrotic PCD was activated, but autophagic programmed cell death was not observed. Neither the intrinsic nor extrinsic apoptotic PCD pathway was activated. The granzyme B/perforin-mediated caspase-dependent apoptotic PCD pathway was not activated. CHMP5-scFv retrovirus can neutralize the abnormally high levels of the CHMP5 protein in the cytosol of AML leukemic U937 cells, thereby inducing the programmed cell death of the leukemic cells via AIF-mediated caspase-independent necrosis and apoptosis.

The Effectiveness of self management program on quality of life in patients with sickle cell disease

PubMed Central

Ahmadi, M; Jahani, S; Poormansouri, S; Shariati, A; Tabesh, H

2015-01-01

Background Sickle cell patients suffer from many physical, psychological, and social problems that can affect their quality of life. To deal with this chronic condition and manage their disease and prevent complications associated with the disease, they must learn skills and behaviours. The aim of this study was to determine the effectiveness of self-management programs on quality of life in these patients. Material and Methods Samples of this quasi-experimental study, which included 69 patients with sickle cell disease referring to the Thalassemia Clinic of Shafa Hospital, were entered into the study by census method. Patients received a self-management program using the 5A model for 12 weeks, while their quality of life before the intervention were assessed at the twelfth week and thirty-sixth week using SF-36 questionnaire. Data were analyzed by descriptive statistics, paired t-test, Wilcoxon test, Hotelling's T2, and repeated measures test. Results The eight dimensions and the total QoL score after intervention were significantly increased compared to those before the intervention (P<0.001). Repeated measures test showed that the mean score of eight QoL dimensions and the total QoL score decreased in the thirty-sixth week, compared to twelfth week. However, it was significantly enhanced in comparison with the intervention baseline (P<0.05). Conclusions Current study revealed the efficacy of self-management interventions on the quality of life in patients with sickle cell disease. Therefore, application of this supportive method could be useful to empower the patients and help them to manage the disease. PMID:25914799

2014 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

none,

2014-11-01

The 2014 Annual Progress Report summarizes fiscal year 2014 activities and accomplishments by projects funded by the DOE Hydrogen Program. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing; technology validation; safety, codes and standards; market transformation; and systems analysis.

Predicting performance using background characteristics of international medical graduates in an inner-city university-affiliated Internal Medicine residency training program.

PubMed

Kanna, Balavenkatesh; Gu, Ying; Akhuetie, Jane; Dimitrov, Vihren

2009-07-13

IMGs constitute about a third of the United States (US) internal medicine graduates. US residency training programs face challenges in selection of IMGs with varied background features. However data on this topic is limited. We analyzed whether any pre-selection characteristics of IMG residents in our internal medicine program are associated with selected outcomes, namely competency based evaluation, examination performance and success in acquiring fellowship positions after graduation. We conducted a retrospective study of 51 IMGs at our ACGME accredited teaching institution between 2004 and 2007. Background resident features namely age, gender, self-reported ethnicity, time between medical school graduation to residency (pre-hire time), USMLE step I & II clinical skills scores, pre-GME clinical experience, US externship and interest in pursuing fellowship after graduation expressed in their personal statements were noted. Data on competency-based evaluations, in-service exam scores, research presentation and publications, fellowship pursuance were collected. There were no fellowships offered in our hospital in this study period. Background features were compared between resident groups according to following outcomes: (a) annual aggregate graduate PGY-level specific competency-based evaluation (CBE) score above versus below the median score within our program (scoring scale of 1 - 10), (b) US graduate PGY-level specific resident in-training exam (ITE) score higher versus lower than the median score, and (c) those who succeeded to secure a fellowship within the study period. Using appropriate statistical tests & adjusted regression analysis, odds ratio with 95% confidence intervals were calculated. 94% of the study sample were IMGs; median age was 35 years (Inter-Quartile range 25th - 75th percentile (IQR): 33-37 years); 43% women and 59% were Asian physicians. The median pre-hire time was 5 years (IQR: 4-7 years) and USMLE step I & step II clinical skills scores

Evaluation program for secondary spacecraft cells: Seventeenth annual report of cycle life test

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1981-01-01

Acceptance tests were conducted on nickel cadmium, silver cadmium, and silver zinc cells to insure that all cells put into the life cycle program meet the specifications outlined in the respective purchase contracts. Statistical information is presented on cell performance characteristics and limitations. Weaknesses discovered in cell design are reported and aid in research and development efforts toward improving the reliability of space batteries. Battery weaknesses encountered in satellite programs such as IMP, NIMBUS, OGO, OAO, SAS, and TETR were studied and remedied through special tests.

DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

PubMed

Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

2007-04-01

The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

At the Edge of Translation – Materials to Program Cells for Directed Differentiation

PubMed Central

Arany, Praveen R; Mooney, David J

2010-01-01

The rapid advancement in basic biology knowledge, especially in the stem cell field, has created new opportunities to develop biomaterials capable of orchestrating the behavior of transplanted and host cells. Based on our current understanding of cellular differentiation, a conceptual framework for the use of materials to program cells in situ is presented, namely a domino versus a switchboard model, to highlight the use of single versus multiple cues in a controlled manner to modulate biological processes. Further, specific design principles of material systems to present soluble and insoluble cues that are capable of recruiting, programming and deploying host cells for various applications are presented. The evolution of biomaterials from simple inert substances used to fill defects, to the recent development of sophisticated material systems capable of programming cells in situ is providing a platform to translate our understanding of basic biological mechanisms to clinical care. PMID:20860763

Time-course of programmed cell death during leaf senescence in Eucommia ulmoides.

PubMed

Cao, Jing; Jiang, Feng; Sodmergen; Cui, Keming

2003-02-01

Leaves of Eucommia ulmoidesOliv. harvested between April to November were examined for programmed cell death (PCD) during growth and senescence. Leaves developed in April, becoming fully expanded in late May, remaining unchanged until November when they started to dehisce. Falling leaves retained a green color. Our results showed that (1) mesophyll cells gradually reduced their nuclei from September to November, (2) positive TUNEL signals appeared on the nuclei from August, (3) ladder-like DNA fragmentation occurred in September and October, and (4) a 20-kDa Ca(2+)-dependent DNase appeared in these same months. In fallen leaves, intact mesophyll cell nuclei could not be detected, but a few cells around the vascular bundle had nuclei. Therefore, (1) programmed cell death (PCD) of leaf cells occurred in the leaves of E. ulmoides, (2) the progress of mesophyll cell PCD lasted for more than 2 months, and (3) PCD of leaf cells was asynchronous in natural senescing leaves.

Quenched substrates for live-cell labeling of SNAP-tagged fusion proteins with improved fluorescent background.

PubMed

Stöhr, Katharina; Siegberg, Daniel; Ehrhard, Tanja; Lymperopoulos, Konstantinos; Öz, Simin; Schulmeister, Sonja; Pfeifer, Andrea C; Bachmann, Julie; Klingmüller, Ursula; Sourjik, Victor; Herten, Dirk-Peter

2010-10-01

Recent developments in fluorescence microscopy raise the demands for bright and photostable fluorescent tags for specific and background free labeling in living cells. Aside from fluorescent proteins and other tagging methods, labeling of SNAP-tagged proteins has become available thereby increasing the pool of potentially applicable fluorescent dyes for specific labeling of proteins. Here, we report on novel conjugates of benzylguanine (BG) which are quenched in their fluorescence and become highly fluorescent upon labeling of the SNAP-tag, the commercial variant of the human O(6)-alkylguanosyltransferase (hAGT). We identified four conjugates showing a strong increase, i.e., >10-fold, in fluorescence intensity upon labeling of SNAP-tag in vitro. Moreover, we screened a subset of nine BG-dye conjugates in living Escherichia coli and found them all suited for labeling of the SNAP-tag. Here, quenched BG-dye conjugates yield a higher specificity due to reduced contribution from excess conjugate to the fluorescence signal. We further extended the application of these conjugates by labeling a SNAP-tag fusion of the Tar chemoreceptor in live E. coli cells and the eukaryotic transcription factor STAT5b in NIH 3T3 mouse fibroblast cells. Aside from the labeling efficiency and specificity in living cells, we discuss possible mechanisms that might be responsible for the changes in fluorescence emission upon labeling of the SNAP-tag, as well as problems we encountered with nonspecific labeling with certain conjugates in eukaryotic cells.

Summary of Fuel Cell Programs at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Perez-Davis, Marla

2000-01-01

The objective of this program is to develop passive ancillary component technology to be teamed with a hydrogen-oxygen unitized regenerative fuel cell (URFC) stack to form a revolutionary new regenerative fuel cell energy (RFC) storage system for aerospace applications. Replacement of active RFC ancillary components with passive components minimizes parasitic power losses and allows the RFC to operate as a H2/O2 battery. The goal of this program is to demonstrate an integrated passive lkW URFC system.

Hodgkin/Reed-Sternberg cells and Hodgkin's disease in patients with B-cell chronic lymphocytic leukaemia: an immunohistological, molecular and clinical study of four cases suggesting a heterogeneous pathogenetic background.

PubMed

Pescarmona, E; Pignoloni, P; Mauro, F R; Cerretti, R; Anselmo, A P; Mandelli, F; Baroni, C D

2000-08-01

We report the immunohistological, molecular and clinical findings in four patients affected by B-cell chronic lymphocytic leukaemia (CLL) who developed "Richter's syndrome with Hodgkin's disease (HD) features" or "CLL with Hodgkin's transformation", all characterised by the presence of typical Hodgkin/Reed-Sternberg (H/RS) cells in lymph node biopsies. In three cases the nodal involvement by CLL was demonstrated both by the presence of a predominant background of CD5/CD19/CD23+ small lymphocytes and an IgH monoclonal rearrangement revealed by PCR analysis. Conversely, in the remaining case there was neither immunohistological nor molecular evidence of lymph node involvement by CLL. In all four cases H/RS cells were Epstein-Barr virus (EBV) latent membrane protein (LMP-1) positive. These findings suggest that the presence of H/RS cells in the first three patients, who had CLL/HD nodal involvement, might be related to transformation or clonal evolution of CLL cells in H/RS cells, which is in keeping with use of the term "CLL with Hodgkin's transformation". In the fourth case a de novo HD may be postulated, representing a second malignancy presumably not clonally related to CLL. In all cases a key pathogenetic role of EBV is suggested by the expression of LMP-1 in H/RS cells. Our findings indicate that the presence of typical H/RS cells in lymph node biopsies in CLL patients may reflect a heterogeneous pathogenetic background. The different clinico-pathologic settings should be taken into consideration because of their possible implications for patients' treatment and prognosis.

Onsite 40-kilowatt fuel cell power plant manufacturing and field test program

NASA Technical Reports Server (NTRS)

1985-01-01

A joint Gas Research Institute and U.S. Department of Energy Program was initiated in 1982 to evaluate the use of fuel cell power systems for on-site energy service. Forty-six 40 kW fuel cell power plants were manufactured at the United Technologies Corporation facility in South Windsor, Connecticut, and are being delivered to host utilities and other program participants in the United States and Japan for field testing. The construction of the 46 fully-integrated power plants was completed in January 1985 within the constraints of the contract plan. The program has provided significant experience in the manufacture, acceptance testing, deployment, and support of on-site fuel cell systems. Initial field test results also show that these experimental power plants meet the performance and environmental requirements of a commercial specification. This Interim Report encompasses the design and manufacturing phases of the 40 kW Power Plant Manufacturing and Field Test program. The contract between UTC and NASA also provides UTC field engineering support to the host utilities, training programs and associated manuals for utility operating and maintenance personnel, spare parts support for a defined test period, and testing at UTC of a power plant made available from a preceding program phase. These activities are ongoing and will be reported subsequently.

Genetic programs can be compressed and autonomously decompressed in live cells

NASA Astrophysics Data System (ADS)

Lapique, Nicolas; Benenson, Yaakov

2018-04-01

Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes1-13 and genetically encoded circuits in live cells14-21. Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity22 of two bits per nucleotide23. In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum24. We hypothesize that the biological function of a genetic program can be preserved while reducing the length of its DNA encoding and increasing the information content per nucleotide. Here we support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we choose an RNAi cell classifier circuit25 that comprises redundant DNA sequences and is therefore amenable for compression, as are many other complex gene circuits15,18,26-28. In one example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs. The compression principles applied to gene circuits can enable fitting complex genetic programs into DNA delivery vehicles with limited cargo capacity, and storing compressed and biologically inert programs in vivo for on-demand activation.

A Fluorogenic TMP-tag for High Signal-to-Background Intracellular Live Cell Imaging

PubMed Central

Jing, Chaoran

2013-01-01

Developed to compliment the use of fluorescent proteins in live cell imaging, chemical tags enjoy the benefit of modular incorporation of organic fluorophores, opening the possibility of high photon output and special photophysical properties. However, the theoretical challenge in using chemical tags as opposed to fluorescent proteins for high-resolution imaging is background noise from unbound and/or non-specifically bound ligand-fluorophore. We envisioned we could overcome this limit by engineering fluorogenic trimethoprim-based chemical tags (TMP-tags) in which the fluorophore is quenched until binding with E. coli dihydrofolate reductase (eDHFR) tagged protein displaces the quencher. Thus, we began by building a non-fluorogenic, covalent TMP-tag based on a proximity-induced reaction known to achieve rapid and specific labeling both in vitro and inside of living cells. Here we take the final step and render the covalent TMP-tag fluorogenic. In brief, we designed a trimeric TMP-fluorophore-quencher molecule (TMP-Q-Atto520) with the quencher attached to a leaving group that, upon TMP binding to eDHFR, would be cleaved by a cysteine residue (Cys) installed just outside the binding pocket of eDHFR. We present the in vitro experiments showing that the eDHFR:L28C nucleophile cleaves the TMP-Q-Atto520 rapidly and efficiently, resulting in covalent labeling and remarkable fluorescence enhancement. Most significantly, while only our initial design, TMP-Q-Atto520 achieved the demanding goal of not only labeling highly abundant, localized intracellular proteins, but also less abundant, more dynamic cytoplasmic proteins. These results suggest that fluorogenic TMP-tag can significantly impact highresolution live cell imaging and further establish the potential of proximity-induced reactivity and organic chemistry more broadly as part of the growing toolbox for synthetic biology and cell engineering. PMID:23745575

Aging of perennial cells and organ parts according to the programmed aging paradigm.

PubMed

Libertini, Giacinto; Ferrara, Nicola

2016-04-01

If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

Programming Enzyme-Initiated Autonomous DNAzyme Nanodevices in Living Cells.

PubMed

Chen, Feng; Bai, Min; Cao, Ke; Zhao, Yue; Cao, Xiaowen; Wei, Jing; Wu, Na; Li, Jiang; Wang, Lihua; Fan, Chunhai; Zhao, Yongxi

2017-12-26

Molecular nanodevices are computational assemblers that switch defined states upon external stimulation. However, interfacing artificial nanodevices with natural molecular machineries in living cells remains a great challenge. Here, we delineate a generic method for programming assembly of enzyme-initiated DNAzyme nanodevices (DzNanos). Two programs including split assembly of two partzymes and toehold exchange displacement assembly of one intact DNAzyme initiated by telomerase are computed. The intact one obtains higher assembly yield and catalytic performance ascribed to proper conformation folding and active misplaced assembly. By employing MnO 2 nanosheets as both DNA carriers and source of Mn 2+ as DNAzyme cofactor, we find that this DzNano is well assembled via a series of conformational states in living cells and operates autonomously with sustained cleavage activity. Other enzymes can also induce corresponding DzNano assembly with defined programming modules. These DzNanos not only can monitor enzyme catalysis in situ but also will enable the implementation of cellular stages, behaviors, and pathways for basic science, diagnostic, and therapeutic applications as genetic circuits.

Oxidative Stress and Programmed Cell Death in Yeast

PubMed Central

Farrugia, Gianluca; Balzan, Rena

2012-01-01

Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed. PMID:22737670

Posttranscriptional (Re)programming of Cell Fate: Examples in Stem Cells, Progenitor, and Differentiated Cells.

PubMed

Kanellopoulou, Chrysi; Muljo, Stefan A

2018-01-01

How a single genome can give rise to many different transcriptomes and thus all the different cell lineages in the human body is a fundamental question in biology. While signaling pathways, transcription factors, and chromatin architecture, to name a few determinants, have been established to play critical roles, recently, there is a growing appreciation of the roles of non-coding RNAs and RNA-binding proteins in controlling cell fates posttranscriptionally. Thus, it is vital that these emerging players are also integrated into models of gene regulatory networks that underlie programs of cellular differentiation. Sometimes, we can leverage knowledge about such posttranscriptional circuits to reprogram patterns of gene expression in meaningful ways. Here, we review three examples from our work.

Proposed low-cost premarital screening program for prevention of sickle cell and thalassemia in Yemen

PubMed Central

Al-Nood, Hafiz; Al-Hadi, Abdulrahman

2013-01-01

In Yemen, the prevalence of sickle cell trait and β-thalassemia trait are high. The aim of this premarital program is to identify sickle cell and thalassemia carrier couples in Yemen before completing marriages proposal, in order to prevent affected birth. This can be achieved by applying a low-cost premarital screening program using simple blood tests compatible with the limited health resources of the country. If microcytosis or positive sickle cell is found in both or one partner has microcytosis and the other has positive sickle cell, so their children at high risk of having sickle cell or/and thalassemia diseases. Carrier couples will be referred to genetic counseling. The outcomes of this preventive program are predicted to decrease the incidence of affected birth and reduce the health burden of these disorders. The success of this program also requires governmental, educational and religious supports. PMID:25003062

Background Oriented Schlieren Implementation in a Jet-Surface Interaction Test

NASA Technical Reports Server (NTRS)

Clem, Michelle M.; Brown, Clifford A.; Fagan, Amy

2013-01-01

Many current and future aircraft designs rely on the wing or other aircraft surfaces to shield the engine noise from observers on the ground. However the available data regarding how a planar surface interacts with a jet to shield and/or enhance the jet noise are currently limited. Therefore, the Jet-Surface Interaction Tests supported by NASA's Fundamental Aeronautics Program's Fixed Wing Project were undertaken to supply experimental data covering a wide range of surface geometries and positions interacting with high-speed jet flows in order to support the development of noise prediction methods. Phase 1 of the Test was conducted in the Aero-Acoustic Propulsion Laboratory at NASA Glenn Research Center and consisted of validating noise prediction schemes for a round nozzle interacting with a planar surface. Phased array data and far-field acoustic data were collected for both the shielded and reflected sides of the surface. Phase 1 results showed that the broadband shock noise was greatly reduced by the surface when the jet was operated at the over-expanded condition, however, it was unclear whether this reduction was due a change in the shock cell structure by the surface. In the present study, Background Oriented Schlieren is implemented in Phase 2 of the Jet-Surface Interaction Tests to investigate whether the planar surface interacts with the high-speed jet ow to change the shock cell structure. Background Oriented Schlieren data are acquired for under-expanded, ideally-expanded, and over-expanded ow regimes for multiple axial and radial positions of the surface at three different plate lengths. These data are analyzed with far-field noise measurements to relate the shock cell structure to the broadband shock noise produced by a jet near a surface.

Coast Guard Cutter Procurement: Background and Issues for Congress

DTIC Science & Technology

2013-07-24

strategy for the OPC; Coast Guard Cutter Procurement: Background and Issues for Congress Congressional Research Service • the potential for using...Acquisition Strategy ........................................................... 24 2012 Testimony...Guard’s funding requests and acquisition strategies for the NSC, OPC, and FRC programs. Congress’s decisions on these three programs could

Results of the 1980 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Seaman, C. H.; Weiss, R. S.

1981-01-01

Thirty-eight modules were carried to an altitude of about 36 kilometers. In addition to the cell calibration program, an experiment to evaluate the calibration error versus altitude was performed. The calibrated cells can be used as reference standards in simulator testing of cells and arrays.

Discussing a Philosophical Background for the Ethnomathematical Program

ERIC Educational Resources Information Center

Vilela, Denise Silva

2010-01-01

This article examines the extent to which Wittgenstein's analytical framework may be relevant to philosophical reflection on ethnomathematics. The discussion develops Bill Barton's suggestion that a philosophical basis for the ethnomathematical program should include and explain culturally different mathematics systems, and the coexistence of…

'You find yourself.' Perceptions of nursing students from non-English speaking backgrounds of the effect of an intensive language support program on their oral clinical communication skills.

PubMed

Rogan, Fran; San Miguel, Caroline; Brown, Di; Kilstoff, Kathleen

2006-10-01

Nurses of ethnically diverse backgrounds are essential in providing multicultural populations in western societies with culturally and linguistically competent health care. However, many nurses from non-English speaking backgrounds (NESB) are at high risk of failure in university programs particularly during clinical placements. Few studies investigate the clinical experiences of students from NESB and strategies to support their learning. This study describes perceptions of fifteen undergraduate nursing students from NESB about their first clinical placement in an Australian university program and the effect of a language support program on their oral clinical communication skills. Three categories arose: *Wanting to belong but feeling excluded; *Wanting to learn how to...; and *You find yourself. While many students find clinical placement challenging, it appeared difficult for students in this study as language and cultural adjustments required some modification of their usual ways of thinking and communicating, often without coping strategies available to other students.

Results of the 1984 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Downing, R. G.; Weiss, R. S.

1984-01-01

The 1984 solar cell calibration balloon flight was successfully completed on July 19, meeting all objectives of the program. Thirty-six modules were carried to an altitude of 36.0 kilometers. The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1982 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Downing, R. G.; Weiss, R. S.

1983-01-01

The 1982 solar cell calibration balloon flight was successfully completed on July 21, meeting all objectives of the program. Twenty-eight modules were carried to an altitude of 36.0 kilometers. The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1983 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Downing, R. G.; Weiss, R. S.

1984-01-01

The 1983 solar cell calibration balloon flight was successfully completed and met all objectives of the program. Thirty-four modules were carried to an altitude of 36.0 kilometers. The calibrated cells can now be used as reference standards in simulator testing of cells and arrays. Cell calibration data are tabulated as well as the repeatability of standard solar cell BFS-17A (35 flights over a 21-year period).

Spinosad induces programmed cell death involves mitochondrial dysfunction and cytochrome C release in Spodoptera frugiperda Sf9 cells.

PubMed

Yang, Mingjun; Wang, Bo; Gao, Jufang; Zhang, Yang; Xu, Wenping; Tao, Liming

2017-02-01

Spinosad, a reduced-risk insecticide, acts on the nicotinic acetylcholine receptors and the gamma-aminobutyric acid receptor in the nervous system of target insects. However, its mechanism of action in non-neural insect cells is unclear. This study aimed to evaluate mitochondrial functional changes associated with spinosad in Spodoptera frugiperda (Sf9) insect cells. Our results indicate that in Sf9 cells, spinosad induces programmed cell death and mitochondrial dysfunction through enhanced reactive oxygen species production, mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential collapse, eventually leading to cytochrome C release and apoptosis. The cytochrome C release induced by spinosad treatment was partly inhibited by the mPTP inhibitors cyclosporin A and bongkrekic acid. Subsequently, we found that spinosad downregulated Bcl-2 expression and upregulated p53 and Bax expressions, activated caspase-9 and caspase-3, and triggered PARP cleavage in Sf9 cells. These findings suggested that spinosad-induced programmed cell death was modulated by mitochondrial dysfunction and cytochrome C release. Copyright © 2016 Elsevier Ltd. All rights reserved.

RNA-programmed genome editing in human cells

PubMed Central

Jinek, Martin; East, Alexandra; Cheng, Aaron; Lin, Steven; Ma, Enbo; Doudna, Jennifer

2013-01-01

Type II CRISPR immune systems in bacteria use a dual RNA-guided DNA endonuclease, Cas9, to cleave foreign DNA at specific sites. We show here that Cas9 assembles with hybrid guide RNAs in human cells and can induce the formation of double-strand DNA breaks (DSBs) at a site complementary to the guide RNA sequence in genomic DNA. This cleavage activity requires both Cas9 and the complementary binding of the guide RNA. Experiments using extracts from transfected cells show that RNA expression and/or assembly into Cas9 is the limiting factor for Cas9-mediated DNA cleavage. In addition, we find that extension of the RNA sequence at the 3′ end enhances DNA targeting activity in vivo. These results show that RNA-programmed genome editing is a facile strategy for introducing site-specific genetic changes in human cells. DOI: http://dx.doi.org/10.7554/eLife.00471.001 PMID:23386978

Programming Cell Adhesion for On-Chip Sequential Boolean Logic Functions.

PubMed

Qu, Xiangmeng; Wang, Shaopeng; Ge, Zhilei; Wang, Jianbang; Yao, Guangbao; Li, Jiang; Zuo, Xiaolei; Shi, Jiye; Song, Shiping; Wang, Lihua; Li, Li; Pei, Hao; Fan, Chunhai

2017-08-02

Programmable remodelling of cell surfaces enables high-precision regulation of cell behavior. In this work, we developed in vitro constructed DNA-based chemical reaction networks (CRNs) to program on-chip cell adhesion. We found that the RGD-functionalized DNA CRNs are entirely noninvasive when interfaced with the fluidic mosaic membrane of living cells. DNA toehold with different lengths could tunably alter the release kinetics of cells, which shows rapid release in minutes with the use of a 6-base toehold. We further demonstrated the realization of Boolean logic functions by using DNA strand displacement reactions, which include multi-input and sequential cell logic gates (AND, OR, XOR, and AND-OR). This study provides a highly generic tool for self-organization of biological systems.

Effects of Background Pressure on Relativistic Laser-Plasma Interaction Ion Acceleration

NASA Astrophysics Data System (ADS)

Peterson, Andrew; Orban, C.; Feister, S.; Ngirmang, G.; Smith, J. T.; Klim, A.; Frische, K.; Morrison, J.; Chowdhury, E.; Roquemore, W. M.

2016-10-01

Typically, ultra-intense laser-accelerated ion experiments are carried out under high-vacuum conditions and with a repetition rate up to several shots per day. Looking to the future there is a need to perform these experiments with a much larger repetition rate. A continuously flowing liquid target is more suitable than a solid target for this purpose. However liquids vaporize below their vapor pressure, and the experiment cannot be performed under high-vacuum conditions. The effects of this non-negligible high chamber pressure acceleration of charged particles is not yet well understood. We investigate this phenomena using Particle-in-Cell simulations, exploring the effect of the background pressure on the accelerated ion spectrum. Experiments in this regime are being performed at the Air Force Research Laboratory at Wright-Patterson Air Force Base. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the Air Force Office of Scientific Research, under the management of Dr. Enrique Parra, Program Manager and significant support from the DOD HPCMP Internship Program.

Results of the 1987 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1987-01-01

The 1987 solar cell calibration balloon flight was successfully completed on August 23, 1987, meeting all objectives of the program. Forty-eight modules were carried to an altitude of 120,000 ft (36.0 km). The cells calibrated can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1988 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1988-01-01

The 1988 solar cell calibration balloon flight was successfully completed on August 7, 1988, meeting all objectives of the program. Forty-eight modules were carried to an altitude of 118,000 ft (36.0 km). The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1989 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1989-01-01

The 1989 solar cell calibration balloon flight was successfully completed on August 9, 1989, meeting all objectives of the program. Forty-two modules were carried to an altitude of 118,000 ft (36.0 km). The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1985 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1986-01-01

The 1985 solar cell calibration balloon flight was successfully completed on July 12, 1985, meeting all objectives of the program. Fifty-seven modules were carried to an altitude of 115,000 ft (35.0 km). The calibrated cells can now be used as reference standards in simulator testing of cells and arrays.

The Genetic Program of Pancreatic β-Cell Replication In Vivo

PubMed Central

Klochendler, Agnes; Caspi, Inbal; Corem, Noa; Moran, Maya; Friedlich, Oriel; Elgavish, Sharona; Nevo, Yuval; Helman, Aharon; Glaser, Benjamin; Eden, Amir; Itzkovitz, Shalev

2016-01-01

The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are “left behind” and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo. PMID:26993067

A Flexible Cosmic Ultraviolet Background Model

NASA Astrophysics Data System (ADS)

McQuinn, Matthew

2016-10-01

HST studies of the IGM, of the CGM, and of reionization-era galaxies are all aided by ionizing background models, which are a critical input in modeling the ionization state of diffuse, 10^4 K gas. The ionization state in turn enables the determination of densities and sizes of absorbing clouds and, when applied to the Ly-a forest, the global ionizing emissivity of sources. Unfortunately, studies that use these background models have no way of gauging the amount of uncertainty in the adopted model other than to recompute their results using previous background models with outdated observational inputs. As of yet there has been no systematic study of uncertainties in the background model and there unfortunately is no publicly available ultraviolet background code. A public code would enable users to update the calculation with the latest observational constraints, and it would allow users to experiment with varying the background model's assumptions regarding emissions and absorptions. We propose to develop a publicly available ionizing background code and, as an initial application, quantify the level of uncertainty in the ionizing background spectrum across cosmic time. As the background model improves, so does our understanding of (1) the sources that dominate ionizing emissions across cosmic time and (2) the properties of diffuse gas in the circumgalactic medium, the WHIM, and the Ly-a forest. HST is the primary telescope for studying both the highest redshift galaxies and low-redshift diffuse gas. The proposed program would benefit HST studies of the Universe at z 0 all the way up to z = 10, including of high-z galaxies observed in the HST Frontier Fields.

Tales of cannibalism, suicide, and murder: Programmed cell death in C. elegans.

PubMed

Kinchen, Jason M; Hengartner, Michael O

2005-01-01

"Life is pleasant. Death is peaceful. It's the transition that's troublesome," said Isaac Asimov. Indeed, much scientific work over the last hundred years centered around attempts either to stave off or to induce the onset of death, at both the organismal and the cellular levels. In this quest, the nematode C. elegans has proven an invaluable tool, first, in the articulation of the genetic pathway by which programmed cell death proceeds, and also as a continuing source of inspiration. It is our purpose in this Chapter to familiarize the reader with the topic of programmed cell death in C. elegans and its relevance to current research in the fields of apoptosis and cell corpse clearance.

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Program

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

Weakley, Steven A.

The purpose of the project described in this report is to identify and document the commercial and emerging (projected to be commercialized within the next 3 years) hydrogen and fuel cell technologies and products that resulted from Department of Energy support through the Fuel Cell Technologies (FCT) Program in the Office of Energy Efficiency and Renewable Energy (EERE). Pacific Northwest National Laboratory (PNNL) undertook two efforts simultaneously to accomplish this project. The first effort was a patent search and analysis to identify patents related to hydrogen and fuel cells that are associated with FCT-funded projects (or projects conducted by DOE-EEREmore » predecessor programs) and to ascertain the patents’ current status, as well as any commercial products that may have used the technology documented in the patent. The second effort was a series of interviews with current and past FCT personnel, a review of relevant program annual reports, and an examination of grants made under the Small Business Innovation Research and Small Business Technology Transfer Programs that are related to hydrogen and fuel cells.« less

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Program

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

Weakley, Steven A.; Brown, Scott A.

The purpose of the project described in this report is to identify and document the commercial and emerging (projected to be commercialized within the next 3 years) hydrogen and fuel cell technologies and products that resulted from Department of Energy support through the Fuel Cell Technologies (FCT) Program in the Office of Energy Efficiency and Renewable Energy (EERE). To do this, Pacific Northwest National Laboratory (PNNL) undertook two efforts simultaneously to accomplish this project. The first effort was a patent search and analysis to identify hydrogen- and fuel-cell-related patents that are associated with FCT-funded projects (or projects conducted by DOE-EEREmore » predecessor programs) and to ascertain the patents current status, as well as any commercial products that may have used the technology documented in the patent. The second effort was a series of interviews with current and past FCT personnel, a review of relevant program annual reports, and an examination of hydrogen- and fuel-cell-related grants made under the Small Business Innovation Research and Small Business Technology Transfer Programs, and within the FCT portfolio.« less

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

PubMed Central

Park, Sun-Mi; Gönen, Mithat; Vu, Ly; Minuesa, Gerard; Tivnan, Patrick; Barlowe, Trevor S.; Taggart, James; Lu, Yuheng; Deering, Raquel P.; Hacohen, Nir; Figueroa, Maria E.; Paietta, Elisabeth; Fernandez, Hugo F.; Tallman, Martin S.; Melnick, Ari; Levine, Ross; Leslie, Christina; Lengner, Christopher J.; Kharas, Michael G.

2015-01-01

Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal program and an increase in the differentiation program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential therapeutic target for myeloid leukemia. PMID:25664853

Programmed cell death in seeds of angiosperms.

PubMed

López-Fernández, María Paula; Maldonado, Sara

2015-12-01

During the diversification of angiosperms, seeds have evolved structural, chemical, molecular and physiologically developing changes that specially affect the nucellus and endosperm. All through seed evolution, programmed cell death (PCD) has played a fundamental role. However, examples of PCD during seed development are limited. The present review examines PCD in integuments, nucellus, suspensor and endosperm in those representative examples of seeds studied to date. © 2015 Institute of Botany, Chinese Academy of Sciences.

2014 DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Report

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

none,

2014-10-01

This report summarizes comments from the Peer Review Panel at the 2014 DOE Hydrogen and Fuel Cells Program Annual Merit Review, held on June 16-20, 2014, in Washington, DC. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes, and standards; market transformation; and systems analysis.

2012 DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Report

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

none,

2012-09-01

This report summarizes comments from the Peer Review Panel at the 2012 DOE Hydrogen and Fuel Cells Program Annual Merit Review, held on May 14-18, 2012, in Arlington, Virginia. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes, and standards; education; market transformation; and systems analysis.

2011 DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Report

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

none,

2011-09-01

This report summarizes comments from the Peer Review Panel at the 2011 DOE Hydrogen and Fuel Cells Program Annual Merit Review, held on May 9-13, 2011, in Arlington, Virginia. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes, and standards; education; market transformation; and systems analysis.

2015 DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Report

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

none,

This report summarizes comments from the Peer Review Panel at the 2015 DOE Hydrogen and Fuel Cells Program Annual Merit Review, held on June 8-12, 2015, in Arlington, Virginia. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes, and standards; market transformation; and systems analysis.

CERN-derived analysis of lunar radiation backgrounds

NASA Technical Reports Server (NTRS)

Wilson, Thomas L.; Svoboda, Robert

1993-01-01

The Moon produces radiation which background-limits scientific experiments there. Early analyses of these backgrounds have either failed to take into consideration the effect of charm in particle physics (because they pre-dated its discovery), or have used branching ratios which are no longer strictly valid (due to new accelerator data). We are presently investigating an analytical program for deriving muon and neutrino spectra generated by the Moon, converting an existing CERN computer program known as GEANT which does the same for the Earth. In so doing, this will (1) determine an accurate prompt neutrino spectrum produced by the lunar surface; (2) determine the lunar subsurface particle flux; (3) determine the consequence of charm production physics upon the lunar background radiation environment; and (4) provide an analytical tool for the NASA astrophysics community with which to begin an assessment of the Moon as a scientific laboratory versus its particle radiation environment. This will be done on a recurring basis with the latest experimental results of the particle data groups at Earth-based high-energy accelerators, in particular with the latest branching ratios for charmed meson decay. This will be accomplished for the first time as a full 3-dimensional simulation.

NASA's PEM Fuel Cell Power Plant Development Program for Space Applications

NASA Technical Reports Server (NTRS)

Hoberecht, Mark

2006-01-01

NASA embarked on a PEM fuel cell power plant development program beginning in 2001. This five-year program was conducted by a three-center NASA team of Glenn Research Center (lead), Johnson Space Center, and Kennedy Space Center. The program initially was aimed at developing hardware for a Reusable Launch Vehicle (RLV) application, but more recently had shifted to applications supporting the NASA Exploration Program. The first phase of the development effort, to develop breadboard hardware in the 1-5 kW power range, was conducted by two competing vendors. The second phase of the effort, to develop Engineering Model hardware at the 10 kW power level, was conducted by the winning vendor from the first phase of the effort. Both breadboard units and the single engineering model power plant were delivered to NASA for independent testing. This poster presentation will present a summary of both phases of the development effort, along with a discussion of test results of the PEM fuel cell engineering model under simulated mission conditions.

An Interactive Multimedia Software Program for Exploring Electrochemical Cells.

ERIC Educational Resources Information Center

Greenbowe, Thomas J.

1994-01-01

Describes computer-animated sequences and interactive multimedia instructional programs for use in introductory chemistry which allow students to explore electrochemical cells. The workbench section enables students to manipulate the experimental apparatus, chemicals, and instruments in order to design and build an experiment. The interactive…

Evaluation program for secondary spacecraft cells: Acceptance tests of Eagle-Picher 12.0 ampere-hour nickel-cadmium cells with auxiliary electrodes

NASA Technical Reports Server (NTRS)

Christy, D. E.

1971-01-01

An acceptance test program was conducted on 24 cells to insure that all cells put into the life cycle program were of high quality by the removal of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.150 volts after the cell short test. The cells were rated at 12.0 ampere-hours and equipped with auxiliary electrodes. Test results were: (1) The capacity of the 24 cells ranged from 14.6 to 16.8 ah. All the cells exceeded the rated capacity on all three capacity checks. (2) One cell failed to recover to 1.150 volts after the cell short test. (3) During the overcharge tests, all cells but one failed the test at the c/10 rate after the first minute. (4) A special resistance test was conducted on the auxiliary electrodes of these cells to establish the resistance value necessary which would provide maximum signal power across the auxiliary electrode. The resistance value established was 10 ohms. (5) No electrolyte leakage was observed.

Olfactory cortical adaptation facilitates detection of odors against background.

PubMed

Kadohisa, Mikiko; Wilson, Donald A

2006-03-01

Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.

Programmed Cell Death and Caspase Functions During Neural Development.

PubMed

Yamaguchi, Yoshifumi; Miura, Masayuki

2015-01-01

Programmed cell death (PCD) is a fundamental component of nervous system development. PCD serves as the mechanism for quantitative matching of the number of projecting neurons and their target cells through direct competition for neurotrophic factors in the vertebrate peripheral nervous system. In addition, PCD plays roles in regulating neural cell numbers, canceling developmental errors or noise, and tissue remodeling processes. These findings are mainly derived from genetic studies that prevent cells from dying by apoptosis, which is a major form of PCD and is executed by activation of evolutionarily conserved cysteine protease caspases. Recent studies suggest that caspase activation can be coordinated in time and space at multiple levels, which might underlie nonapoptotic roles of caspases in neural development in addition to apoptotic roles. © 2015 Elsevier Inc. All rights reserved.

Background to new entrant safety fitness assurance process

DOT National Transportation Integrated Search

2000-03-01

This report presents the results of background research leading to the development of a New Entrant Safety Fitness Assurance Process, a prequalification and monitoring program for motor carriers entering interstate service. The New Entrant Safety Fit...

Simulation of PEP-II Accelerator Backgrounds Using TURTLE

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

Barlow, R.J.; Fieguth, T.; /SLAC

2006-02-15

We present studies of accelerator-induced backgrounds in the BaBar detector at the SLAC B-Factory, carried out using LPTURTLE, a modified version of the DECAY TURTLE simulation package. Lost-particle backgrounds in PEP-II are dominated by a combination of beam-gas bremstrahlung, beam-gas Coulomb scattering, radiative-Bhabha events and beam-beam blow-up. The radiation damage and detector occupancy caused by the associated electromagnetic shower debris can limit the usable luminosity. In order to understand and mitigate such backgrounds, we have performed a full program of beam-gas and luminosity-background simulations, that include the effects of the detector solenoidal field, detailed modeling of limiting apertures in bothmore » collider rings, and optimization of the betatron collimation scheme in the presence of large transverse tails.« less

Engineered cell-cell communication via DNA messaging

PubMed Central

2012-01-01

Background Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.” Results We have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis. Conclusions We demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia. PMID:22958599

Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

PubMed

Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

2016-08-04

Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing state stem cell programs in the United States: how has state funding affected publication trends?

PubMed

Alberta, Hillary B; Cheng, Albert; Jackson, Emily L; Pjecha, Matthew; Levine, Aaron D

2015-02-05

Several states responded to federal funding limitations placed on human embryonic stem cell research and the potential of the field by creating state stem cell funding programs, yet little is known about the impact of these programs. Here we examine how state programs have affected publication trends in four states. Copyright © 2015 Elsevier Inc. All rights reserved.

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic programming

PubMed Central

Yang, Kai; Shrestha, Sharad; Zeng, Hu; Karmaus, Peer W.F.; Neale, Geoffrey; Vogel, Peter; Guertin, David A.; Lamb, Richard F.; Chi, Hongbo

2014-01-01

SUMMARY Naïve T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic programming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity. PMID:24315998

[Chronic Disease Self-management Support for People with a Migrant Background: towards a Peer-led Group Program to Improve Equity in Health].

PubMed

Zanoni, S; Gabriel, E; Salis Gross, C; Deppeler, M; Haslbeck, J

2018-03-01

Limited health literacy and language skills are barriers for people with a migrant background (PMB) to access health information and healthcare services, in particular for those living with chronic conditions. During the introduction of a peer-led Stanford chronic disease self-management course in Switzerland, special interest in the program as well as motivation of PMB was observed. In response, we examined if the program can be implemented in German for people with limited language skills. This explorative study is part of the evaluation study on introducing the adapted Stanford program in Switzerland and German-speaking Europe. Following the principles of Grounded Theory, semi-structured focus group and individual interviews were conducted with course participants, leaders and coordinators (n=30) and analyzed thematically. The focus was on the feasibility, satisfaction and course content. In principle, the program seems to have positive value for PMB, may work for them in German, have high relevance for everyday life and give an impetus for social integration. The need for and extent of modification of the program for PMB has to be further explored in order to make it more accessible for vulnerable groups. © Georg Thieme Verlag KG Stuttgart · New York.

Do mitochondria play a role in remodelling lace plant leaves during programmed cell death?

PubMed Central

2011-01-01

Background Programmed cell death (PCD) is the regulated death of cells within an organism. The lace plant (Aponogeton madagascariensis) produces perforations in its leaves through PCD. The leaves of the plant consist of a latticework of longitudinal and transverse veins enclosing areoles. PCD occurs in the cells at the center of these areoles and progresses outwards, stopping approximately five cells from the vasculature. The role of mitochondria during PCD has been recognized in animals; however, it has been less studied during PCD in plants. Results The following paper elucidates the role of mitochondrial dynamics during developmentally regulated PCD in vivo in A. madagascariensis. A single areole within a window stage leaf (PCD is occurring) was divided into three areas based on the progression of PCD; cells that will not undergo PCD (NPCD), cells in early stages of PCD (EPCD), and cells in late stages of PCD (LPCD). Window stage leaves were stained with the mitochondrial dye MitoTracker Red CMXRos and examined. Mitochondrial dynamics were delineated into four categories (M1-M4) based on characteristics including distribution, motility, and membrane potential (ΔΨm). A TUNEL assay showed fragmented nDNA in a gradient over these mitochondrial stages. Chloroplasts and transvacuolar strands were also examined using live cell imaging. The possible importance of mitochondrial permeability transition pore (PTP) formation during PCD was indirectly examined via in vivo cyclosporine A (CsA) treatment. This treatment resulted in lace plant leaves with a significantly lower number of perforations compared to controls, and that displayed mitochondrial dynamics similar to that of non-PCD cells. Conclusions Results depicted mitochondrial dynamics in vivo as PCD progresses within the lace plant, and highlight the correlation of this organelle with other organelles during developmental PCD. To the best of our knowledge, this is the first report of mitochondria and chloroplasts

The Development of Fuel Cell Technology for NASA's Human Spaceflight Program

NASA Technical Reports Server (NTRS)

Scott, John H.

2007-01-01

My task this morning is to review the history and current direction of fuel cell technology development for NASA's human spaceflight program and to compare it to the directions being taken in that field for The Hydrogen Economy. The concept of "The Hydrogen Economy" involves many applications for fuel cells, but for today's discussion, I'll focus on automobiles.

Vehicle Technologies and Fuel Cell Technologies Program: Prospective Benefits Assessment Report for Fiscal Year 2016

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

Stephens, T. S.; Taylor, C. H.; Moore, J. S.

Under a diverse set of programs, the Vehicle Technologies and Fuel Cell Technologies offices of DOE’s Office of Energy Efficiency and Renewable Energy invest in research, development, demonstration, and deployment of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies. This report estimates the benefits of successfully developing and deploying these technologies (a “Program Success” case) relative to a base case (the “No Program” case). The Program Success case represents the future with completely successful deployment of Vehicle Technologies Office (VTO) and Fuel Cell Technologies Office (FCTO) technologies. The No Program case represents a future in which theremore » is no contribution after FY 2016 by the VTO or FCTO to these technologies. The benefits of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies were estimated on the basis of differences in fuel use, primary energy use, and greenhouse gas (GHG) emissions from light-, medium- and heavy-duty vehicles, including energy and emissions from fuel production, between the base case and the Program Success case. Improvements in fuel economy of various vehicle types, growth in the stock of fuel cell vehicles and other advanced technology vehicles, and decreased GHG intensity of hydrogen production and delivery in the Program Success case over the No Program case were projected to result in savings in petroleum use and GHG emissions. Benefits were disaggregated by individual program technology areas, which included the FCTO program and the VTO subprograms of batteries and electric drives; advanced combustion engines; fuels and lubricants; materials (for reduction in vehicle mass, or “lightweighting”); and, for medium- and heavy-duty vehicles, reduction in rolling and aerodynamic resistance. Projections for the Program Success case indicate that by 2035, the average fuel economy of on-road, light-duty vehicle stock could be 47

Cellular programming and reprogramming: sculpting cell fate for the production of dopamine neurons for cell therapy.

PubMed

Aguila, Julio C; Hedlund, Eva; Sanchez-Pernaute, Rosario

2012-01-01

Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.

Vacuolar and cytoskeletal dynamics during elicitor-induced programmed cell death in tobacco BY-2 cells.

PubMed

Higaki, Takumi; Kadota, Yasuhiro; Goh, Tatsuaki; Hayashi, Teruyuki; Kutsuna, Natsumaro; Sano, Toshio; Hasezawa, Seiichiro; Kuchitsu, Kazuyuki

2008-09-01

Responses of plant cells to environmental stresses often involve morphological changes, differentiation and redistribution of various organelles and cytoskeletal network. Tobacco BY-2 cells provide excellent model system for in vivo imaging of these intracellular events. Treatment of the cell cycle-synchronized BY-2 cells with a proteinaceous oomycete elicitor, cryptogein, induces highly synchronous programmed cell death (PCD) and provide a model system to characterize vacuolar and cytoskeletal dynamics during the PCD. Sequential observation revealed dynamic reorganization of the vacuole and actin microfilaments during the execution of the PCD. We further characterized the effects cryptogein on mitotic microtubule organization in cell cycle-synchronized cells. Cryptogein treatment at S phase inhibited formation of the preprophase band, a cortical microtubule band that predicts the cell division site. Cortical microtubules kept their random orientation till their disruption that gradually occurred during the execution of the PCD twelve hours after the cryptogein treatment. Possible molecular mechanisms and physiological roles of the dynamic behavior of the organelles and cytoskeletal network in the pathogenic signal-induced PCD are discussed.

On the origin, evolution, and nature of programmed cell death: a timeline of four billion years.

PubMed

Ameisen, J C

2002-04-01

Programmed cell death is a genetically regulated process of cell suicide that is central to the development, homeostasis and integrity of multicellular organisms. Conversely, the dysregulation of mechanisms controlling cell suicide plays a role in the pathogenesis of a wide range of diseases. While great progress has been achieved in the unveiling of the molecular mechanisms of programmed cell death, a new level of complexity, with important therapeutic implications, has begun to emerge, suggesting (i) that several different self-destruction pathways may exist and operate in parallel in our cells, and (ii) that molecular effectors of cell suicide may also perform other functions unrelated to cell death induction and crucial to cell survival. In this review, I will argue that this new level of complexity, implying that there may be no such thing as a 'bona fide' genetic death program in our cells, might be better understood when considered in an evolutionary context. And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms.

Hemoglobins, programmed cell death and somatic embryogenesis.

PubMed

Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

2013-10-01

Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival. Copyright © 2013 Elsevier Ireland Ltd

The Effect of Background Pressure on Electron Acceleration from Ultra-Intense Laser-Matter Interactions

NASA Astrophysics Data System (ADS)

Le, Manh; Ngirmang, Gregory; Orban, Chris; Morrison, John; Chowdhury, Enam; Roquemore, William

2017-10-01

We present two-dimensional particle-in-cell (PIC) simulations that investigate the role of background pressure on the acceleration of electrons from ultra intense laser interaction at normal incidence with liquid density ethylene glycol targets. The interaction was simulated at ten different pressures varying from 7.8 mTorr to 26 Torr. We calculated conversion efficiencies from the simulation results and plotted the efficiencies with respect to the background pressure. The results revealed that the laser to > 100 keV electron conversion efficiency remained flat around 0.35% from 7.8 mTorr to 1.2 Torr and increased exponentially from 1.2 Torr onward to about 1.47% at 26 Torr. Increasing the background pressure clearly has a dramatic effect on the acceleration of electrons from the target. We explain how electrostatic effects, in particular the neutralization of the target by the background plasma, allows electrons to escape more easily and that this effect is strengthened with higher densities. This work could facilitate the design of future experiments in increasing laser to electron conversion efficiency and generating substantial bursts of electrons with relativistic energies. This research is supported by the Air Force Office of Scientific Research under LRIR Project 17RQCOR504 under the management of Dr. Riq Parra and Dr. Jean-Luc Cambier. Support was also provided by the DOD HPCMP Internship Program.

Low-background detector arrays for infrared astronomy

NASA Technical Reports Server (NTRS)

Mccreight, C. R.; Estrada, J. A.; Goebel, J. H.; Mckelvey, M. E.; Mckibbin, D. D.; Mcmurray, R. E., Jr.; Weber, T. T.

1989-01-01

The status of a program which develops and characterizes integrated infrared (IR) detector array technology for space astronomical applications is described. The devices under development include intrinsic, extrinsic silicon, and extrinsic germanium detectors, coupled to silicon readout electronics. Low-background laboratory test results include measurements of responsivity, noise, dark current, temporal response, and the effects of gamma-radiation. In addition, successful astronomical imagery has been obtained on some arrays from this program. These two aspects of the development combine to demonstrate the strong potential for integrated array technology for IR space astronomy.

The Genetic Program of Pancreatic β-Cell Replication In Vivo.

PubMed

Klochendler, Agnes; Caspi, Inbal; Corem, Noa; Moran, Maya; Friedlich, Oriel; Elgavish, Sharona; Nevo, Yuval; Helman, Aharon; Glaser, Benjamin; Eden, Amir; Itzkovitz, Shalev; Dor, Yuval

2016-07-01

The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are "left behind" and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Analysis of 12 AH aerospace nickel-cadmium cells from the design variable program

NASA Technical Reports Server (NTRS)

Vasanth, Kunigahalli L.; Morrow, George

1987-01-01

The Design Variable Program of NASA/GSFC provided a systematic approach to evaluate the performance of 12 Ampere-Hour Nickel-Cadmium cells of different designs. Design Variables tested in this program included teflonated negative plates, silver treated negative plates, lightly loaded negative plates, positive plates with no cadmium treatment, plate design of 1968 utilizing old and new processing techniques and electrochemically impregnated positive plates. These cells were life cycled in a Low-Earth Orbit (LEO) regime for 3 to 4 years. Representative cells taken from the Design Variable Program were examined via chemical, electrochemical and surface analyses. The results indicate the following: (1) positive swelling and carbonate content in the electrolyte increase as a function of number of cycles; (2) electrolyte distribution follows a general order NEG greater than POS greater than SEP; (3) control and No PQ groups outperformed the rest of the groups; and (4) the polyproylene group exhibited heavy cadmium migration and poor performance.

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

PubMed

Velasco, Silvia; Ibrahim, Mahmoud M; Kakumanu, Akshay; Garipler, Görkem; Aydin, Begüm; Al-Sayegh, Mohamed Ahmed; Hirsekorn, Antje; Abdul-Rahman, Farah; Satija, Rahul; Ohler, Uwe; Mahony, Shaun; Mazzoni, Esteban O

2017-02-02

Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic. Copyright © 2017 Elsevier Inc. All rights reserved.

Egypt: Background and U.S. Relations

DTIC Science & Technology

2009-05-12

contributions from Germany , Japan, and Switzerland. For more information on the MFO, see http://www.mfo.org/Default.asp?bhcp=1. Egypt: Background and...2008 Report, Egypt’s pace of business reforms and deregulation between 2006 and 2007 ranked first worldwide. In recent years, the state has...reinvigorated its privatization program by divesting shares in the state-dominated banking and insurance sectors. Additionally, the government removed import

Concise review: programming human pluripotent stem cells into blood.

PubMed

Easterbrook, Jennifer; Fidanza, Antonella; Forrester, Lesley M

2016-06-01

Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future. © 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Differential Expression of Programmed Cell Death on the Follicular Development in Normal and Miniature Pig Ovary

PubMed Central

Kim, Sang Hwan; Min, Kwan Sik; Kim, Nam Hyung; Yoon, Jong Taek

2012-01-01

Follicles are important in oocyte maturation. Successful estrous cycle requires remodeling of follicular cells, and proper execution of programmed cell death is crucial for normal follicular development. The objectives of the present study were to understand programmed cell death during follicle development, to analyze the differential follicle development patterns, and to assess the patterns of apoptosis and autophagy expression during follicle development in normal and miniature pigs. Through the analysis of differential patterns of programmed cell death during follicular development in porcine, MAP1LC3A, B and other autophagy-associated genes (ATG5, mTOR, Beclin-1) were found to increase in normal pigs, while it decreased in miniature pigs. However, for the apoptosis-associated genes, progression of genes during follicular development increased in miniature pigs, while it decreased in normal pigs. Thus, results show that normal and miniature pigs showed distinct patterns of follicular remodeling manifesting that programmed cell death largely depends on the types of pathway during follicular development (Type II or autophagy for normal pigs and Type I or apoptosis for miniature pigs). PMID:23056260

Death of mitochondria during programmed cell death of leaf mesophyll cells.

PubMed

Selga, Tūrs; Selga, Maija; Pāvila, Vineta

2005-12-01

The role of plant mitochondria in the programmed cell death (PCD) is widely discussed. However, spectrum and sequence of mitochondrial structural changes during different types of PCD in leaves are poorly described. Pea, cucumber and rye plants were grown under controlled growing conditions. A part of them were sprinkled with ethylene releaser to accelerate cell death. During yellowing the palisade parenchyma mitochondria were attracted to nuclear envelope. Mitochondrial matrix became electron translucent. Mitochondria entered vacuole by invagination of tonoplast and formed multivesicular bodies. Ethephon treatment increased the frequency of sticking of mitochondria to the nuclear envelope or chloroplasts and peroxisomes. Mitochondria divided by different mechanisms and became enclosed in Golgi and ER derived authopagic vacuoles or in the central vacuole. Several fold increase of the diameter of cristae became typical. In all cases mitochondria were attached to nuclear envelope. It can be considered as structural mechanism of promoting of PCD.

The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

PubMed Central

Gaidt, Moritz M.; Ebert, Thomas S.; Chauhan, Dhruv; Ramshorn, Katharina; Pinci, Francesca; Zuber, Sarah; O’Duill, Fionan; Schmid-Burgk, Jonathan L.; Hoss, Florian; Buhmann, Raymund; Wittmann, Georg; Latz, Eicke; Subklewe, Marion; Hornung, Veit

2018-01-01

Summary Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3. Forward genetics identified regulators of lysosomal trafficking to modulate this cell death program, and subsequent studies revealed that activated STING traffics to the lysosome, where it triggers membrane permeabilization and thus lysosomal cell death (LCD). Importantly, the cGAS-STING-NLRP3 pathway constitutes the default inflammasome response during viral and bacterial infections in human myeloid cells. We conclude that targeting the cGAS-STING-LCD-NLRP3 pathway will ameliorate pathology in inflammatory conditions that are associated with cytosolic DNA sensing. PMID:29033128

Determination of an Environmental Background Level of Sr-90 in Urine for the Hanford Bioassay Program Determination of an Environmental Background Level of Sr-90 in Urine for the Hanford Bioassay Program

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

Antonio, Cheryl L.; Rivard, James W.

2009-11-01

During the decommissioning and maintenance of some of the facilities at the U.S. Department of Energy Hanford Site in Washington State, workers have potential for a 90Sr intake. However, because of worldwide radioactive fallout, 90Sr is present in our environment, and can be detectable in routine urine bioassay samples. It is important for the Hanford Site bioassay program to discern an occupational intake from a non-occupational environmental one. A detailed study of the background 90Sr in the urine of unexposed Hanford workers was performed. A survey of the Hanford Site bioassay database found 128 Hanford workers who were hired betweenmore » 1997 and 2002 and who had a very low potential for an occupational exposure prior to the baseline strontium urinalysis. Each urinalysis sample represented excretion during an approximate 24-hr period. The arithmetic mean value for the 128 pre-exposure baselines was 3.6 ± 5.1 mBq d-1. The 90Sr activities in urine varied from -12 to 20 mBq. The 99th percentile result was 16.4 mBqd-1, which was interpreted to mean that 1% of Hanford workers not occupationally exposed to strontium might exceed 16.4 mBq d-1.« less

The Shc protein RAI promotes an adaptive cell survival program in hypoxic neuroblastoma cells.

PubMed

Criscuoli, Mattia; Filippi, Irene; Osti, Daniela; Aldinucci, Carlo; Guerrini, Giuditta; Pelicci, Giuliana; Carraro, Fabio; Naldini, Antonella

2018-05-01

Neuroblastoma (NB) is a highly malignant pediatric solid tumor where a hypoxic signature correlates with unfavorable patient outcome. The hypoxia-inducible factor (HIF)-1α plays an important role in NB progression, contributing to cell proliferation and invasiveness. RAI belongs to the Shc family proteins, it is mainly neuron specific and protects against cerebral ischemia. RAI is also expressed in several NB cell lines, where it promotes cell survival. In this work, hypoxia differently affected cell survival and pro-apoptotic program in two NB cell lines, either expressing RAI (SKNBE) or not (SKNMC). RAI expression appeared to promote NB cell survival and to reduce some pro-apoptotic markers under hypoxia. Accordingly, the RAI silencing in SKNBE cells resulted in a reduction of cell survival and HIF-1α expression. Furthermore, using SKNMC cells stably expressing RAI, we defined a role of RAI in NB cell responses to hypoxia. Of interest, in hypoxic SKNMC cells expressing RAI HIF-1α protein levels were higher than in control cells. This was associated with a) an increased cell survival; b) an increased expression of anti-apoptotic markers; c) a pro-autophagic and not pro-apoptotic phenotype; and d) an increased metabolic activity. We may conclude that RAI plays an important role in hypoxic signaling in NB cells and the interplay between RAI and HIF-1α may be relevant in the protection of NB cells against hypoxia. Our results may contribute to a further understanding the physiology of NB cells and the molecular mechanisms involved in their survival, with important implications in NB progression. © 2017 Wiley Periodicals, Inc.

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

PubMed Central

López-Arencibia, Atteneri; Sifaoui, Ines; Reyes-Batlle, María; Valladares, Basilio; Martínez-Carretero, Enrique; Piñero, José E.; Maciver, Sutherland K.; Lorenzo-Morales, Jacob

2015-01-01

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a life-threatening encephalitis. In order to treat those infections properly, it is necessary to target the treatment not only to the trophozoite but also to the cyst. Furthermore, it may be advantageous to avoid parasite killing by necrosis, which may induce local inflammation. We must also avoid toxicity of host tissue. Many drugs which target eukaryotes are known to induce programmed cell death (PCD), but this process is poorly characterized in Acanthamoeba. Here, we study the processes of programmed cell death in Acanthamoeba, induced by several drugs, such as statins and voriconazole. We tested atorvastatin, fluvastatin, simvastatin, and voriconazole at the 50% inhibitory concentrations (IC50s) and IC90s that we have previously established. In order to evaluate this phenomenon, we investigated the DNA fragmentation, one of the main characteristics of PCD, with quantitative and qualitative techniques. Also, the changes related to phosphatidylserine exposure on the external cell membrane and cell permeability were studied. Finally, because caspases are key to PCD pathways, caspase activity was evaluated in Acanthamoeba. All the drugs assayed in this study induced PCD in Acanthamoeba. To the best of our knowledge, this is the first study where PCD induced by drugs is described quantitatively and qualitatively in Acanthamoeba. PMID:25733513

Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells

NASA Astrophysics Data System (ADS)

Yang, Lili; Baltimore, David

2005-03-01

A method to genetically program mouse hematopoietic stem cells to develop into functional CD8 or CD4 T cells of defined specificity in vivo is described. For this purpose, a bicistronic retroviral vector was engineered that efficiently delivers genes for both and chains of T cell receptor (TCR) to hematopoietic stem cells. When modified cell populations were used to reconstruct the hematopoietic lineages of recipient mice, significant percentages of antigen-specific CD8 or CD4 T cells were observed. These cells expressed normal surface markers and responded to peptide antigen stimulation by proliferation and cytokine production. Moreover, they could mature into memory cells after peptide stimulation. Using TCRs specific for a model tumor antigen, we found that the recipient mice were able to partially resist a challenge with tumor cells carrying the antigen. By combining cells modified with CD8- and CD4-specific TCRs, and boosting with dendritic cells pulsed with cognate peptides, complete suppression of tumor could be achieved and even tumors that had become established would regress and be eliminated after dendritic cell/peptide immunization. This methodology of "instructive immunotherapy" could be developed for controlling the growth of human tumors and attacking established pathogens.

Current status of Westinghouse tubular solid oxide fuel cell program

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

Parker, W.G.

1996-04-01

In the last ten years the solid oxide fuel cell (SOFC) development program at Westinghouse has evolved from a focus on basic material science to the engineering of fully integrated electric power systems. Our endurance for this cell is 5 to 10 years. To date we have successfully operated at power for over six years. For power plants it is our goal to have operated before the end of this decade a MW class power plant. Progress toward these goals is described.

Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis

PubMed Central

2014-01-01

Introduction A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients. Methods Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-γ) and interleukin-2 (IL-2) production were quantitated by flow cytometry. Results Lymphocytes from septic patients produced decreased IFN-γ and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-γ, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-γ and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01). Conclusions In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results

Role of genetic background in induced instability

NASA Technical Reports Server (NTRS)

Kadhim, Munira A.; Nelson, G. A. (Principal Investigator)

2003-01-01

Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

Biomaterials for the programming of cell growth in oral tissues: The possible role of APA.

PubMed

Salerno, Marco; Giacomelli, Luca; Larosa, Claudio

2011-01-06

Examples of programmed tissue response after the interaction of cells with biomaterials are a hot topic in current dental research. We propose here the use of anodic porous alumina (APA) for the programming of cell growth in oral tissues. In particular, APA may trigger cell growth by the controlled release of specific growth factors and/or ions. Moreover, APA may be used as a scaffold to promote generation of new tissue, due to the high interconnectivity of pores and the high surface roughness displayed by this material.

Difference in suitable mechanical properties of three-dimensional, synthetic scaffolds for self-renewing mouse embryonic stem cells of different genetic backgrounds.

PubMed

Lee, Myungook; Ahn, Jong Il; Ahn, Ji Yeon; Yang, Woo Sub; Hubbell, Jeffrey A; Lim, Jeong Mook; Lee, Seung Tae

2017-11-01

We evaluated whether the genetic background of embryonic stem cells (ESCs) affects the properties suitable for three-dimensional (3D) synthetic scaffolds for cell self-renewal. Inbred R1 and hybrid B6D2F1 mouse ESC lines were cultured for 7 days in hydrogel scaffolds with different properties derived from conjugating 7.5, 10, 12.5, or 15% (wt/vol) vinylsulfone-functionalized three-, four-, or eight-arm polyethylene glycol (PEG) with dicysteine-containing crosslinkers with an intervening matrix metalloproteinase-specific cleavage sites. Cell proliferation and expression of self-renewal-related genes and proteins by ESCs cultured in feeder-free or containing 2D culture plate or 3D hydrogel were monitored. As a preliminary experiment, the E14 ESC-customized synthetic 3D microenvironment did not maintain self-renewal of either the R1 or B6D2F1 ESCs. The best R1 cell proliferation (10.04 vs. 0.16-4.39; p < 0.0001) was observed in the four-arm 7.5% PEG-based hydrogels than those with other properties, whereas the F1 ESCs showed better proliferation when they were embedded in the three-arm 10% hydrogels. Self-renewal-related gene and protein expression by ESCs after feeder-free 3D culture was generally maintained compared with the feeder-containing 2D culture, but expression patterns and quantities differed. However, the feeder-free 3D culture yielded better expression than the feeder-free 2D culture. In conclusion, genetic background determined the suitability of hydrogel scaffolds for self-renewal of ESCs, which requires customization for the mechanical properties of each cell line. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2261-2268, 2017. © 2016 Wiley Periodicals, Inc.

Effects of Elevated Pax6 Expression and Genetic Background on Mouse Eye Development

PubMed Central

Chanas, Simon A.; Collinson, J. Martin; Ramaesh, Thaya; Dorà, Natalie; Kleinjan, Dirk A.; Hill, Robert E.; West, John D.

2009-01-01

Purpose To analyze the effects of Pax6 overexpression and its interaction with genetic background on eye development. Methods Histologic features of eyes from hemizygous PAX77+/− transgenic (high Pax6 gene dose) and wild-type mice were compared on different genetic backgrounds. Experimental PAX77+/−↔wild-type and control wild-type↔wild-type chimeras were analyzed to investigate the causes of abnormal eye development in PAX77+/− mice. Results PAX77+/− mice showed an overlapping but distinct spectrum of eye abnormalities to Pax6+/− heterozygotes (low Pax6 dose). Some previously reported PAX77+/− eye abnormalities did not occur on all three genetic backgrounds examined. Several types of eye abnormalities occurred in the experimental PAX77+/−↔wild-type chimeras, and they occurred more frequently in chimeras with higher contributions of PAX77+/− cells. Groups of RPE cells intruded into the optic nerve sheath, indicating that the boundary between the retina and optic nerve may be displaced. Both PAX77+/− and wild-type cells were involved in this ingression and in retinal folds, suggesting that neither effect was cell-autonomous. Cell-autonomous effects included failure of PAX77+/− and wild-type cells to mix normally and overrepresentation of PAX77+/− in the lens epithelium and RPE. Conclusions The extent of PAX77+/− eye abnormalities depended on PAX77+/− genotype, genetic background, and stochastic variation. Chimera analysis identified two types of cell-autonomous effects of the PAX77+/− genotype. Abnormal cell mixing between PAX77+/− and wild-type cells suggests altered expression of cell surface adhesion molecules. Some phenotypic differences between PAX77+/−↔wild-type and Pax6+/−↔wild-type chimeras may reflect differences in the levels of PAX77+/− and Pax6+/− contributions to chimeric lenses. PMID:19387074

Results of the 1994 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1994-01-01

The 1994 solar cell calibration balloon flight was completed on August 6, 1994. All objectives of the flight program were met. Thirty-seven modules were carried to an altitude of 119,000 ft (36.6 km). Data telemetered from the modules was corrected to 28 C and to 1 AU. The calibrated cells have been returned to the 6 participants and can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1991 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1991-01-01

The 1991 solar cell calibration balloon flight was completed on August 1, 1991. All objectives of the flight program were met. Thirty-nine modules were carried to an altitude of 119,000 ft. (36.3 km). Data telemetered from the modules were corrected to 28 C and to 1 AU. The calibrated cells have been returned to the participants and can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1992 NASA/JPL Balloon Flight Solar Cell Calibration Program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1992-01-01

The 1992 solar cell calibration balloon flight was completed on August 1, 1992. All objectives of the flight program were met. Forty-one modules were carried to an altitude of 119,000 ft (36.3 km). Data telemetered from the modules was corrected to 28 C and 1 AU. The calibrated cells have been returned to 39 participants and can now be used as reference standards in simulator testing of cells and arrays.

Results of the 1993 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1993-01-01

The 1993 solar cell calibration balloon flight was completed on July 29, 1993. All objectives of the flight program were met. Forty modules were carried to an altitude of 120,000 ft (36.6 km). Data telemetered from the modules was corrected to 28 C and to 1 AU. The calibrated cells have been returned to 8 participants and can now be used as reference standards in simulator testing of cells and arrays.

The effects of mothers’ musical background on sedentary behavior, physical activity, and exercise adherence in their 5-6-years-old children using movement-to-music video program

PubMed Central

Raitanen, Jani; Husu, Pauliina; Kujala, Urho M.; Luoto, Riitta M.

2018-01-01

Objectives The purpose of this study was to examine whether mothers’ musical background has an effect on their own and their children’s sedentary behavior (SB) and physical activity (PA). The aim was also to assess children’s and their mothers’ exercise adherence when using movement-to-music video program. Design Sub-group analysis of an intervention group in a randomized controlled trial (ISRCTN33885819). Method Seventy-one mother-child-pairs were divided into two categories based on mothers’ musical background. Each pair performed 8 weeks exercise intervention using movement-to-music video program. SB and PA were assessed objectively by accelerometer, and exercise activity, fidelity, and enjoyment were assessed via exercise diaries and questionnaires. Logistic regression model was used to analyze associations in the main outcomes between the groups. Results Those children whose mothers had musical background (MB) had greater probability to increase their light PA during the intervention, but not moderate-to-vigorous PA compared to those children whose mothers did not have musical background (NMB). SB increased in both groups. Mothers in the NMB group had greater probability to increase their light and moderate-to-vigorous PA and decrease their SB than mothers in the MB group. However, exercise adherence decreased considerably in all groups. Completeness, fidelity, and enjoyment were higher among the NMB group compared to the MB group. Conclusions The present results showed that mothers without musical background were more interested in movement-to-music exercises, as well as their children. For further studies it would be important to evaluate an effect of children’s own music-based activities on their SB and PA. PMID:29668726

The 4.5 inch diameter IPV Ni-H2 cell development program

NASA Technical Reports Server (NTRS)

Miller, L.

1986-01-01

Interest in larger capacity Ni-H2 battery cells for space applications has resulted in the initiation of a development/qualification/production program. Cell component design was completed and component hardware fabricated and/or delivered. Finished cell design projections demonstrate favorable specific energies in the range of 70 to 75 Whr/Kg (32 to 34 Whr/Lb) for capacities of 100 to 250 Ah. It is further planned during this effort to evaluate the advanced cell design technology which has evolved from the work conducted at the NASA/Lewis Research Center.

The 4.5 inch diameter IPV Ni-H2 cell development program

NASA Astrophysics Data System (ADS)

Miller, L.

1986-09-01

Interest in larger capacity Ni-H2 battery cells for space applications has resulted in the initiation of a development/qualification/production program. Cell component design was completed and component hardware fabricated and/or delivered. Finished cell design projections demonstrate favorable specific energies in the range of 70 to 75 Whr/Kg (32 to 34 Whr/Lb) for capacities of 100 to 250 Ah. It is further planned during this effort to evaluate the advanced cell design technology which has evolved from the work conducted at the NASA/Lewis Research Center.

Bachelor of Science-Engineering Technology Program and Fuel Cell Education Program Concentration

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

Block, David L.; Sleiti, Ahmad

2011-09-19

The Hydrogen and Fuel Cell Technology education project has addressed DOE goals by supplying readily available, objective, technical, and accurate information that is available to students, industry and the public. In addition, the program has supplied educated trainers and training opportunities for the next generation workforce needed for research, development, and demonstration activities in government, industry, and academia. The project has successfully developed courses and associated laboratories, taught the new courses and labs and integrated the HFCT option into the accredited engineering technology and mechanical engineering programs at the University of North Carolina at Charlotte (UNCC). The project has alsomore » established ongoing collaborations with the UNCC energy related centers of the Energy Production & Infrastructure Center (EPIC), the NC Motorsports and Automotive Research Center (NCMARC) and the Infrastructure, Design, Environment and Sustainability Center (IDEAS). The results of the project activities are presented as two major areas – (1) course and laboratory development, offerings and delivery, and (2) program recruitment, promotions and collaborations. Over the project period, the primary activity has been the development and offering of 11 HFCT courses and accompanying laboratories. This process has taken three years with the courses first being developed and then offered each year over the timeframe.« less

Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells

PubMed Central

Chen, Ling; Sham, Caroline W.; Chan, Ann M.; Francisco, Loise M.; Wu, Yin; Mareninov, Sergey; Sharpe, Arlene H.; Freeman, Gordon J.; Yang, Xian-Jie; Braun, Jonathan; Gordon, Lynn K.

2011-01-01

PURPOSE Mammalian programmed cell death-1 (PD-1) is a membrane-associated receptor regulating the balance between T cell activation, tolerance and immunopathology, however its role in neurons has not yet been defined. We investigate the hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina. METHODS Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retina explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS PD-1 is expressed in most adult RGCs, and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases survival of RGCs. Furthermore, PD-1 deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, throughout postnatal retina maturation, we find gene expression of both immune PD-1 ligand genes, PD-L1 and PD-L2. CONCLUSIONS These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation. PMID:19420345

A Conserved Core of Programmed Cell Death Indicator Genes Discriminates Developmentally and Environmentally Induced Programmed Cell Death in Plants.

PubMed

Olvera-Carrillo, Yadira; Van Bel, Michiel; Van Hautegem, Tom; Fendrych, Matyáš; Huysmans, Marlies; Simaskova, Maria; van Durme, Matthias; Buscaill, Pierre; Rivas, Susana; Coll, Nuria S.; Coppens, Frederik; Maere, Steven; Nowack, Moritz K.

2015-12-01

A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta. © 2015 American Society of Plant Biologists. All Rights Reserved.

Results of the Air Force high efficiency cascaded multiple bandgap solar cell programs

NASA Technical Reports Server (NTRS)

Rahilly, W. P.

1980-01-01

The III-V semiconductor materials system that was selected for continued cascade cell development was the AlGaAs cell on GaAs cell structure. The tunnel junction used as transparent ohmic contact between the top cell and the bottom cell continued to be the central difficulty in achieving the program objective of 25 percent AMO efficiency at 25 C. During the tunnel junction and top cell developments it became apparent that the AlGaAs cell has potential for independent development as a single junction converter and is a logical extension of the present GaAs heteroface technology.

Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming.

PubMed

Zhao, Ting; Fu, Yao; Zhu, Jialiang; Liu, Yifang; Zhang, Qian; Yi, Zexuan; Chen, Shi; Jiao, Zhonggang; Xu, Xiaochan; Xu, Junquan; Duo, Shuguang; Bai, Yun; Tang, Chao; Li, Cheng; Deng, Hongkui

2018-06-12

Chemical reprogramming provides a powerful platform for exploring the molecular dynamics that lead to pluripotency. Although previous studies have uncovered an intermediate extraembryonic endoderm (XEN)-like state during this process, the molecular underpinnings of pluripotency acquisition remain largely undefined. Here, we profile 36,199 single-cell transcriptomes at multiple time points throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs are key aspects of successful reprogramming from XEN-like state to pluripotency, including the concomitant transcriptomic signatures of two-cell (2C) embryonic-like and early pluripotency programs and the epigenetic signature of notable genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by fine-tuning chemical treatment, the reprogramming process is remarkably accelerated. Collectively, our findings offer a high-resolution dissection of cell fate dynamics during chemical reprogramming and shed light on mechanistic insights into the nature of induced pluripotency. Copyright © 2018 Elsevier Inc. All rights reserved.

Pollen tube reuses intracellular components of nucellar cells undergoing programmed cell death in Pinus densiflora.

PubMed

Hiratsuka, Rie; Terasaka, Osamu

2011-04-01

Through the process known as programmed cell death (PCD), nucelli of Pinus densiflora serve as the transmitting tissue for growth of the pollen tube. We sought to clarify the processes of degradation of nucellar cell components and their transport to the pollen tube during PCD in response to pollen tube penetration of such nucelli. Stimulated by pollination, synthesis of large amounts of starch grains occurred in cells in a wide region of the nucellus, but as the pollen tube penetrated the nucellus, starch grains were degraded in amyloplasts of nucellar cells. In cells undergoing PCD, electron-dense vacuoles with high membrane contrast appeared, assumed a variety of autophagic structures, expanded, and ultimately collapsed and disappeared. Vesicles and electron-dense amorphous materials were released inside the thickened walls of cells undergoing PCD, and those vesicles and materials reaching the pollen tube after passing through the extracellular matrix were taken into the tube by endocytosis. These results show that in PCD of nucellar cells, intracellular materials are degraded in amyloplasts and vacuoles, and some of the degraded material is supplied to the pollen tube by vesicular transport to support tube growth.

Phosphoric acid fuel cell power plant system performance model and computer program

NASA Technical Reports Server (NTRS)

Alkasab, K. A.; Lu, C. Y.

1984-01-01

A FORTRAN computer program was developed for analyzing the performance of phosphoric acid fuel cell power plant systems. Energy mass and electrochemical analysis in the reformer, the shaft converters, the heat exchangers, and the fuel cell stack were combined to develop a mathematical model for the power plant for both atmospheric and pressurized conditions, and for several commercial fuels.

Genetic background effects in Neuroligin-3 mutant mice: Minimal behavioral abnormalities on C57 background.

PubMed

Jaramillo, Thomas C; Escamilla, Christine Ochoa; Liu, Shunan; Peca, Lauren; Birnbaum, Shari G; Powell, Craig M

2018-02-01

Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein that interacts with presynaptic ligands including neurexin-1 (NRXN1) [Ichtchenko et al., Journal of Biological Chemistry, 271, 2676-2682, 1996]. Mice harboring a mutation in the NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism spectrum disorder (ASD) were previously generated and behaviorally phenotyped for autism-related behaviors. In these NL3R451C mice generated and tested on a hybrid C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and reduced social interaction [Tabuchi et al., Science, 318, 71-76, 2007]. Curiously, an independently generated second line of mice harboring the same mutation on a C57BL6J background exhibited minimal aberrant behavior, thereby providing apparently discrepant results. To investigate the origin of the discrepancy, we previously replicated the original findings of Tabuchi et al. by studying the same NL3R451C mutation on a pure 129S2/SvPasCrl genetic background. Here we complete the behavioral characterization of the NL3R451C mutation on a pure C57BL6J genetic background to determine if background genetics play a role in the discrepant behavioral outcomes involving NL3R451C mice. NL3R451C mutant mice on a pure C57BL6J background did not display spatial memory enhancements or social interaction deficits. We only observed a decreased startle response and mildly increased locomotor activity in these mice suggesting that background genetics influences behavioral outcomes involving the NL3R451C mutation. Autism Res 2018, 11: 234-244. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Behavioral symptoms of autism can be highly variable, even in cases that involve identical genetic mutations. Previous studies in mice with a mutation of the Neuroligin-3 gene showed enhanced learning and social deficits. We replicated these findings on the same and different genetic backgrounds. In this study, however, the

Chronically Ill Children in America: Background and Recommendations.

ERIC Educational Resources Information Center

Hobbs, Nicholas; And Others

The report examines chronic illness in children and considers issues and recommendations for change in public policies and programs affecting chronically ill children and their families. The background chapter notes the significance of the problem, reviews 11 diseases that are representative of the severe chronic illnesses of childhood: juvenile…

Live to die another way: modes of programmed cell death and the signals emanating from dying cells

PubMed Central

Fuchs, Yaron; Steller, Hermann

2015-01-01

Preface All life ends in death, but perhaps one of life’s grander ironies is that it also depends on death. Cell-intrinsic suicide pathways, termed programmed cell death (PCD), are crucial for animal development, tissue homeostasis and pathogenesis. Originally, PCD was virtually synonymous with apoptosis, but recently, alternative PCD mechanisms have been reported. Here, we provide an overview of several distinct PCD mechanisms, namely apoptosis, autophagy and necroptosis. In addition, we discuss the complex signals emanating from dying cells, which can either fuel regeneration or instruct additional killing. Further advances in understanding the physiological role of multiple cell death mechanisms and associated signals will be important to selectively manipulate PCD for therapeutic purposes. PMID:25991373

Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.

PubMed

Pfeiffer, Martin J; Quaranta, Roberto; Piccini, Ilaria; Fell, Jakob; Rao, Jyoti; Röpke, Albrecht; Seebohm, Guiscard; Greber, Boris

2018-01-30

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart-yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent EOMES induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells.

Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies.

PubMed

Kelling, F J; Ialenti, F; Den Otter, C J

2002-06-01

The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross-adaptation and cross-sensitization between a background odour of (+/-)-1-octen-3-ol and pulses of (+/-)-1-octen-3-ol, 2-pentanone and R-(+)-limonene can occur, confirming that olfactory receptor cells are sensitive to different odours. Background odour can increase the responses to low concentration odour pulses and decrease the responses to higher concentration odour pulses. It is suggested that background odour has a larger effect on olfactory receptor cells that respond with a tonic increase of spike frequency, giving information about the level of odour concentration, i.e. the 'static' environment. Cells that respond in a phasic way only provide information on the dynamics of the olfactory environment.

Design of Light Trapping Solar Cell System by Using Zemax Program

NASA Astrophysics Data System (ADS)

Hasan, A. B.; Husain, S. A.

2018-05-01

Square micro lenses array have been designed (by using Zemax optical design program) to concentrate solar radiation into variable slits that reaching light to solar cell. This technique to increase the efficiency of solar system by trapping light due to internal reflection of light by mirrors that placed between upper and lower side of solar cell, therefore increasing optical path through the solar cell, and then increasing chance of photon absorption. The results show priority of solar system that have slit of (0.2 mm), and acceptance angle of (20°) that give acceptable efficiency of solar system.

Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company, 6.0 ampere-hour nickel-cadmium spacecraft cells for the GOES-D, E and F satellite program

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1979-01-01

The tests are to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. Test limits specify those values at which a cell is to be terminated from charge or discharge. Requirements are referenced to normally expected values based on past performance of aerospace nickel-cadmium cells with demonstrated life characteristics. Recommendations for the improvement of the manufacturing processes are presented.

Genetic programs constructed from layered logic gates in single cells

PubMed Central

Moon, Tae Seok; Lou, Chunbo; Tamsir, Alvin; Stanton, Brynne C.; Voigt, Christopher A.

2014-01-01

Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics1. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits2–6, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits1,7. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator–chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells. PMID:23041931

Towards programming languages for genetic engineering of living cells.

PubMed

Pedersen, Michael; Phillips, Andrew

2009-08-06

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.

Towards programming languages for genetic engineering of living cells

PubMed Central

Pedersen, Michael; Phillips, Andrew

2009-01-01

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts. PMID:19369220

High repetition rate laser-driven MeV ion acceleration at variable background pressures

NASA Astrophysics Data System (ADS)

Snyder, Joseph; Ngirmang, Gregory; Orban, Chris; Feister, Scott; Morrison, John; Frische, Kyle; Chowdhury, Enam; Roquemore, W. M.

2017-10-01

Ultra-intense laser-plasma interactions (LPI) can produce highly energetic photons, electrons, and ions with numerous potential real-world applications. Many of these applications will require repeatable, high repetition targets that are suitable for LPI experiments. Liquid targets can meet many of these needs, but they typically require higher chamber pressure than is used for many low repetition rate experiments. The effect of background pressure on the LPI has not been thoroughly studied. With this in mind, the Extreme Light group at the Air Force Research Lab has carried out MeV ion and electron acceleration experiments at kHz repetition rate with background pressures ranging from 30 mTorr to >1 Torr using a submicron ethylene glycol liquid sheet target. We present these results and provide two-dimensional particle-in-cell simulation results that offer insight on the thresholds for the efficient acceleration of electrons and ions. This research is supported by the Air Force Office of Scientific Research under LRIR Project 17RQCOR504 under the management of Dr. Riq Parra and Dr. Jean-Luc Cambier. Support was also provided by the DOD HPCMP Internship Program.

Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells

PubMed Central

Liao, Yunfei; Chen, Lulu; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

2017-01-01

Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma. PMID:28415820

Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells.

PubMed

Liao, Yunfei; Chen, Lulu; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

2017-05-02

Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma.

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-04-10

Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK...Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead, the Chief of Naval...question is whether the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile development programs. A 2005 defense

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-09-18

and Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f...October 27, 2008. Another press report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures... aligned with foreign-country ballistic missile development programs. A 2005 defense trade press report, for example, states that “navy officials

Nonsmall Cell Lung Carcinoma with Giant Cell Features Expressing Programmed Death-Ligand 1: A Report of a Patient Successfully Treated with Pembrolizumab

PubMed Central

Nakayama, Shingo; Sasaki, Mamoru; Morinaga, Shojiroh

2018-01-01

Giant cell carcinoma, a rare variant of nonsmall cell lung carcinoma (NSCLC), is characterized by aggressive progression and poor response to conventional chemotherapy. This report is the first to describe a patient with NSCLC and giant cell features who was successfully treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). A 69-year-old woman was diagnosed with NSCLC with multiple brain metastases. Histological evaluation of lung biopsy specimens revealed proliferation of pleomorphic giant tumor cells with poor cohesiveness, findings consistent with giant cell carcinoma. Immunostaining showed that a high proportion of the tumor cells were positive for expression of programmed death-ligand 1 (PD-L1). The patient received stereotactic radiotherapy for the brain metastases, followed by administration of pembrolizumab. Treatment with pembrolizumab resulted in the rapid regression of the primary lung nodule, with the progression-free period maintained for at least four treatment cycles. Immunotherapy targeting PD-1/PD-L1 may be an option for patients with PD-L1-positive NSCLC with giant cell features. PMID:29736285

Nonsmall Cell Lung Carcinoma with Giant Cell Features Expressing Programmed Death-Ligand 1: A Report of a Patient Successfully Treated with Pembrolizumab.

PubMed

Nakayama, Shingo; Sasaki, Mamoru; Morinaga, Shojiroh; Minematsu, Naoto

2018-01-01

Giant cell carcinoma, a rare variant of nonsmall cell lung carcinoma (NSCLC), is characterized by aggressive progression and poor response to conventional chemotherapy. This report is the first to describe a patient with NSCLC and giant cell features who was successfully treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). A 69-year-old woman was diagnosed with NSCLC with multiple brain metastases. Histological evaluation of lung biopsy specimens revealed proliferation of pleomorphic giant tumor cells with poor cohesiveness, findings consistent with giant cell carcinoma. Immunostaining showed that a high proportion of the tumor cells were positive for expression of programmed death-ligand 1 (PD-L1). The patient received stereotactic radiotherapy for the brain metastases, followed by administration of pembrolizumab. Treatment with pembrolizumab resulted in the rapid regression of the primary lung nodule, with the progression-free period maintained for at least four treatment cycles. Immunotherapy targeting PD-1/PD-L1 may be an option for patients with PD-L1-positive NSCLC with giant cell features.

Beyond Introductory Programming: Success Factors for Advanced Programming

ERIC Educational Resources Information Center

Hoskey, Arthur; Maurino, Paula San Millan

2011-01-01

Numerous studies document high drop-out and failure rates for students in computer programming classes. Studies show that even when some students pass programming classes, they still do not know how to program. Many factors have been considered to explain this problem including gender, age, prior programming experience, major, math background,…

Does a Rater's Professional Background Influence Communication Skills Assessment?

PubMed

Artemiou, Elpida; Hecker, Kent G; Adams, Cindy L; Coe, Jason B

2015-01-01

There is increasing pressure in veterinary education to teach and assess communication skills, with the Objective Structured Clinical Examination (OSCE) being the most common assessment method. Previous research reveals that raters are a large source of variance in OSCEs. This study focused on examining the effect of raters' professional background as a source of variance when assessing students' communication skills. Twenty-three raters were categorized according to their professional background: clinical sciences (n=11), basic sciences (n=4), clinical communication (n=5), or hospital administrator/clinical skills technicians (n=3). Raters from each professional background were assigned to the same station and assessed the same students during two four-station OSCEs. Students were in year 2 of their pre-clinical program. Repeated-measures ANOVA results showed that OSCE scores awarded by the rater groups differed significantly: (F(matched_station_1) [2,91]=6.97, p=.002), (F(matched_station_2) [3,90]=13.95, p=.001), (F(matched_station_3) [3,90]=8.76, p=.001), and ((Fmatched_station_4) [2,91]=30.60, p=.001). A significant time effect between the two OSCEs was calculated for matched stations 1, 2, and 4, indicating improved student performances. Raters with a clinical communication skills background assigned scores that were significantly lower compared to the other rater groups. Analysis of written feedback provided by the clinical sciences raters showed that they were influenced by the students' clinical knowledge of the case and that they did not rely solely on the communication checklist items. This study shows that it is important to consider rater background both in recruitment and training programs for communication skills' assessment.

Unfolding a chordate developmental program, one cell at a time: invariant cell lineages, short-range inductions and evolutionary plasticity in ascidians.

PubMed

Lemaire, Patrick

2009-08-01

Ascidians were historically the first metazoans in which experimental embryology was carried out. These early works by Chabry and Conklin [Chabry, L., 1887. Embryologie normale et tératologique des Ascidie. Felix Alcan Editeur, Paris; Conklin, E., 1905. The organization and cell lineage of the ascidian egg. J. Acad., Nat. Sci. Phila. 13, 1], in particular, led to the idea that the developmental program of these animals was driven by the cell-autonomous inheritance of localised maternal determinants, rendered precise by the stereotyped pattern of invariant cell cleavages. Work in the past 20 years indeed identified several localised maternal determinants of the position of cleavage planes or of some early cell fates. The overwhelming majority of cells in the three germ layers, however, do not follow a cell-autonomous differentiation program. Instead, they respond to short-range signals, as described in this review. Careful analysis of cell-cell contacts suggests that a major function of the invariant position of cleavage plans, besides segregating competence factors, is to control the relative positions of inducing cells and those competent to respond. Surprisingly, while the cell lineage is very well conserved between the divergent species Halocynthia roretzi and Ciona intestinalis, the molecular nature of inducing signals can vary. The constraints on embryo anatomy thus appear stronger than those on the choice of individual regulatory molecules.

Only in dying, life: programmed cell death during plant development.

PubMed

Van Hautegem, Tom; Waters, Andrew J; Goodrich, Justin; Nowack, Moritz K

2015-02-01

Programmed cell death (PCD) is a fundamental process of life. During the evolution of multicellular organisms, the actively controlled demise of cells has been recruited to fulfil a multitude of functions in development, differentiation, tissue homeostasis, and immune systems. In this review we discuss some of the multiple cases of PCD that occur as integral parts of plant development in a remarkable variety of cell types, tissues, and organs. Although research in the last decade has discovered a number of PCD regulators, mediators, and executers, we are still only beginning to understand the mechanistic complexity that tightly controls preparation, initiation, and execution of PCD as a process that is indispensable for successful vegetative and reproductive development of plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Issues and progress in determining background ozone and particle concentrations

NASA Astrophysics Data System (ADS)

Pinto, J. P.

2011-12-01

Exposure to ambient ozone is associated with a variety of health outcomes ranging from mild breathing discomfort to mortality. For the purpose of health risk and policy assessments EPA evaluates the anthropogenic increase in ozone above background concentrations and has defined the North American (NA) background concentration of O3 as that which would occur in the U.S. in the absence of anthropogenic emissions of precursors in the U.S., Canada, and Mexico. Monthly average NA background ozone has been used to evaluate health risks, but EPA and state air quality managers must also estimate day specific ozone background levels for high ozone episodes as part of urban scale photochemical modeling efforts to support ozone regulatory programs. The background concentration of O3 is of more concern than other air pollutants because it typically represents a much larger fraction of observed O3 than do the backgrounds of other criteria pollutants (particulate matter (PM), CO, NO2, SO2). NA background cannot be determined directly from ambient monitoring data because of the influence of NA precursor emissions on formation of ozone within NA. Instead, estimates of NA background O3 have been based on GEOS-Chem using simulations in which NA anthropogenic precursor emissions are zeroed out. Thus, modeled NA background O3 includes contributions from natural sources of precursors (including CH4, NMVOCs, NOx, and CO) everywhere in the world, anthropogenic sources of precursors outside of NA, and downward transport of O3 from the stratosphere. Although monitoring data cannot determine NA background directly, measurements by satellites, aircraft, ozonesondes and surface monitors have proved to be highly useful for identifying sources of background O3 and for evaluating the performance of the GEOS-Chem model. Model simulated NA background concentrations are strong functions of location and season with large inter-day variability and with values increasing with elevation and higher in

Senescent cells re-engineered to express soluble programmed death receptor-1 for inhibiting programmed death receptor-1/programmed death ligand-1 as a vaccination approach against breast cancer.

PubMed

Chen, Zehong; Hu, Kang; Feng, Lieting; Su, Ruxiong; Lai, Nan; Yang, Zike; Kang, Shijun

2018-06-01

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1 + T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis.

PubMed

Tsai, FuNien; Perlman, Harris; Cuda, Carla M

2017-12-01

Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Alpha Backgrounds in DarkSide-50

NASA Astrophysics Data System (ADS)

Monte, Alissa; DarkSide Collaboration

2017-01-01

DarkSide-50 is the current phase of the DarkSide direct dark matter search program, operating underground at the Laboratori Nazionali del Gran Sasso in Italy. The detector is a dual-phase argon Time Projection Chamber (TPC), designed for direct detection of Weakly Interacting Massive Particles, and housed within an active veto system of liquid scintillator and water Cherenkov detectors. Since switching to a target of low radioactivity argon extracted from underground sources in April, 2016, the background is no longer dominated by naturally occurring 39Ar. However, alpha backgrounds from radon and its daughters remain, both from the liquid argon bulk and internal detector surfaces. I will present details of the analysis used to understand and quantify alpha backgrounds, as well as to understand other types of radon contamination that may be present, and our sensitivity to them.

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-11-20

and Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK...Another press report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September...whether the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile development programs. A 2005 defense trade

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-10-21

and Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK...Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead, the...related question is whether the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile development programs. A 2005

40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 13 2011-07-01 2011-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system must...

40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 14 2013-07-01 2013-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system must...

40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 14 2012-07-01 2011-07-01 true Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system must...

40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 14 2014-07-01 2014-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system must...

40 CFR Table 8 to Subpart IIIii of... - Requirements for Cell Room Monitoring Program

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 13 2010-07-01 2010-07-01 false Requirements for Cell Room Monitoring... Mercury Cell Chlor-Alkali Plants Pt. 63, Subpt. IIIII, Table 8 Table 8 to Subpart IIIII of Part 63—Requirements for Cell Room Monitoring Program As stated in § 63.8192(g)(1), your mercury monitoring system must...

Regulation of programmed cell death or apoptosis in atherosclerosis.

PubMed

Geng, Y J

1997-01-01

Intimal thickening caused by accumulation of cells, lipids, and connective tissue characterizes atherosclerosis, an arterial disease that leads to cardiac and cerebral infarction. Apoptosis, or genetically programmed cell death, is important for the development and morphogenesis of organs and tissues. As in other tissues, cells of cardiovascular tissues can undergo apoptosis. Increased apoptosis has been found in both human and animal atherosclerotic lesions, mediating tissue turnover and lesion development. In addition to vascular cells, many activated immune cells, mainly macrophages and T cells, are present in atherosclerotic lesions, where these cells produce biologically active substances such as the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1), and interferon-gamma. Simultaneous exposure to these cytokines may trigger apoptosis of vascular smooth muscle cells. The products of death-regulating genes including Fas/Fas ligand, members of IL-1 beta cysteinyl protease (caspase) family, the tumor suppressive gene p53, and the protooncogene c-myc have been found in vascular cells and may participate in the regulation of vascular apoptosis during the development of atherosclerosis. Abnormal occurrence of apoptosis may take place in atherosclerotic lesions, including attenuation or acceleration of the apoptotic death process. The former may cause an increase in the cellularity of the lesions, and the latter can reduce cellular components important for maintaining the integrity and stability of the plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of patients with atherosclerosis and its major complications, heart attack and stroke.

Promyelocytic leukemia zinc finger turns on the effector T cell program without requirement for agonist TCR signaling.

PubMed

Savage, Adam K; Constantinides, Michael G; Bendelac, Albert

2011-05-15

Thymocytes expressing the NKT cell semi-invariant αβ TCR are thought to undergo agonist interactions with CD1d ligands prior to expressing promyelocytic leukemia zinc finger (PLZF), a broad complex, tramtrack, bric-a-brac, poxvirus, and zinc finger transcription factor that directs acquisition of the effector program of these innate-like T cells. Whether PLZF can mediate this effector conversion independently of agonist signaling has not been investigated. We demonstrated that transgenic (Tg) expression of PLZF under the CD4 promoter induced the innate effector program in two different MHC class II-restricted TCR-Tg Rag1(-/-) models examined. In CD4 thymocytes expressing a fixed Tg TCR β-chain, the associated TCRα sequences in wild-type and PLZF-Tg mice overlapped extensively, further demonstrating that PLZF could induce the effector program in most CD4 T cells that would normally be selected as naive cells. In contrast, PLZF altered the negative selection of thymocytes expressing TCR β-chains reactive against several retroviral superantigens. Thus, PLZF is remarkable in that it is a transcription factor capable of inducing an effector program in the absence of T cell agonist interactions or cell division. Its expression may also enhance the survival of agonist-signaled thymocytes.

Results of the 1999 JPL Balloon Flight Solar Cell Calibration Program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Mueller, R. L.; Weiss, R. S.

2000-01-01

The 1999 solar cell calibration balloon flight campaign consisted of two flights, which occurred on June 14, 1999, and July 6, 1999. All objectives of the flight program were met. Fifty-seven modules were carried to an altitude of approximately equal to 120,000 ft (36.6 km). Full I-V curves were measured on five of these modules, and output at a fixed load was measured on forty-three modules (forty-five cells), with some modules repeated on the second flight. This data was corrected to 28 C and to 1 AU (1.496 x 10 (exp 8) km). The calibrated cells have been returned to their owners and can now be used as reference standards in simulator testing of cells and arrays.

An Update on the Lithium-Ion Cell Low-Earth-Orbit Verification Test Program

NASA Technical Reports Server (NTRS)

Reid, Concha M.; Manzo, Michelle A.; Miller, Thomas B.; McKissock, Barbara I.; Bennett, William

2007-01-01

A Lithium-Ion Cell Low-Earth-Orbit Verification Test Program is being conducted by NASA Glenn Research Center to assess the performance of lithium-ion (Li-ion) cells over a wide range of low-Earth-orbit (LEO) conditions. The data generated will be used to build an empirical model for Li-ion batteries. The goal of the modeling will be to develop a tool to predict the performance and cycle life of Li-ion batteries operating at a specified set of mission conditions. Using this tool, mission planners will be able to design operation points of the battery system while factoring in mission requirements and the expected life and performance of the batteries. Test conditions for the program were selected via a statistical design of experiments to span a range of feasible operational conditions for LEO aerospace applications. The variables under evaluation are temperature, depth-of-discharge (DOD), and end-of-charge voltage (EOCV). The baseline matrix was formed by generating combinations from a set of three values for each variable. Temperature values are 10 C, 20 C and 30 C. Depth-of-discharge values are 20%, 30% and 40%. EOCV values are 3.85 V, 3.95 V, and 4.05 V. Test conditions for individual cells may vary slightly from the baseline test matrix depending upon the cell manufacturer s recommended operating conditions. Cells from each vendor are being evaluated at each of ten sets of test conditions. Cells from four cell manufacturers are undergoing life cycle tests. Life cycling on the first sets of cells began in September 2004. These cells consist of Saft 40 ampere-hour (Ah) cells and Lith ion 30 Ah cells. These cells have achieved over 10,000 cycles each, equivalent to about 20 months in LEO. In the past year, the test program has expanded to include the evaluation of Mine Safety Appliances (MSA) 50 Ah cells and ABSL battery modules. The MSA cells will begin life cycling in October 2006. The ABSL battery modules consist of commercial Sony hard carbon 18650 lithium

Determination of an environmental background level of 90Sr in urine for the Hanford bioassay program.

PubMed

Antonio, C L; Rivard, J W

2009-11-01

During the decommissioning and maintenance of some of the facilities at the U.S. Department of Energy Hanford Site in Washington State, workers have potential for a Sr intake. However, because of worldwide radioactive fallout, Sr is present in our environment and can be detectable in routine urine bioassay samples. It is important for the Hanford Site bioassay program to discriminate an occupational intake from a non-occupational environmental one. A detailed study of the background Sr in the urine of unexposed Hanford workers was performed. A survey of the Hanford Site bioassay database found 128 Hanford workers who were hired between 1997 and 2002 and who had a very low potential for an occupational exposure prior to the baseline strontium urinalysis. Each urinalysis sample represented excretion during an approximate 24-h period. The arithmetic mean value for the 128 pre-exposure baselines was 3.6 +/- 5.1 mBq d. The 99 percentile result was 17 mBq d, which was interpreted to mean that 1% of Hanford workers not occupationally exposed to strontium might exceed 17 mBq d.

Current Sickle Cell Screening Program for Newborns in New York City, 1979-1980.

ERIC Educational Resources Information Center

Grover, Ranjeet; And Others

1983-01-01

Screening tests indicated that 141 out of 106,565 infants examined in New York City during 1979-80, had various forms of sickle cell anemia. Follow-up of 131 patients confirmed the original diagnoses, suggesting that the New York City Follow-up Program for Sickle Cell Screening of newborns was successful. (Author/MJL)

Virtual Reality Based Support System for Layout Planning and Programming of an Industrial Robotic Work Cell

PubMed Central

Yap, Hwa Jen; Taha, Zahari; Md Dawal, Siti Zawiah; Chang, Siow-Wee

2014-01-01

Traditional robotic work cell design and programming are considered inefficient and outdated in current industrial and market demands. In this research, virtual reality (VR) technology is used to improve human-robot interface, whereby complicated commands or programming knowledge is not required. The proposed solution, known as VR-based Programming of a Robotic Work Cell (VR-Rocell), consists of two sub-programmes, which are VR-Robotic Work Cell Layout (VR-RoWL) and VR-based Robot Teaching System (VR-RoT). VR-RoWL is developed to assign the layout design for an industrial robotic work cell, whereby VR-RoT is developed to overcome safety issues and lack of trained personnel in robot programming. Simple and user-friendly interfaces are designed for inexperienced users to generate robot commands without damaging the robot or interrupting the production line. The user is able to attempt numerous times to attain an optimum solution. A case study is conducted in the Robotics Laboratory to assemble an electronics casing and it is found that the output models are compatible with commercial software without loss of information. Furthermore, the generated KUKA commands are workable when loaded into a commercial simulator. The operation of the actual robotic work cell shows that the errors may be due to the dynamics of the KUKA robot rather than the accuracy of the generated programme. Therefore, it is concluded that the virtual reality based solution approach can be implemented in an industrial robotic work cell. PMID:25360663

Virtual reality based support system for layout planning and programming of an industrial robotic work cell.

PubMed

Yap, Hwa Jen; Taha, Zahari; Dawal, Siti Zawiah Md; Chang, Siow-Wee

2014-01-01

Traditional robotic work cell design and programming are considered inefficient and outdated in current industrial and market demands. In this research, virtual reality (VR) technology is used to improve human-robot interface, whereby complicated commands or programming knowledge is not required. The proposed solution, known as VR-based Programming of a Robotic Work Cell (VR-Rocell), consists of two sub-programmes, which are VR-Robotic Work Cell Layout (VR-RoWL) and VR-based Robot Teaching System (VR-RoT). VR-RoWL is developed to assign the layout design for an industrial robotic work cell, whereby VR-RoT is developed to overcome safety issues and lack of trained personnel in robot programming. Simple and user-friendly interfaces are designed for inexperienced users to generate robot commands without damaging the robot or interrupting the production line. The user is able to attempt numerous times to attain an optimum solution. A case study is conducted in the Robotics Laboratory to assemble an electronics casing and it is found that the output models are compatible with commercial software without loss of information. Furthermore, the generated KUKA commands are workable when loaded into a commercial simulator. The operation of the actual robotic work cell shows that the errors may be due to the dynamics of the KUKA robot rather than the accuracy of the generated programme. Therefore, it is concluded that the virtual reality based solution approach can be implemented in an industrial robotic work cell.

Development of criteria used to establish a background environmental monitoring station

DOE PAGES

Fritz, Brad G.; Barnett, J. Matthew; Snyder, Sandra F.; ...

2015-03-02

It is generally considered necessary to measure concentrations of contaminants-of-concern at a background location when conducting atmospheric environmental surveillance. This is because it is recognized that measurements of background concentrations can enhance interpretation of environmental monitoring data. Despite the recognized need for background measurements, there is little published guidance available that describes how to identify an appropriate atmospheric background monitoring location. This paper develops generic criteria that can guide the decision making process for identifying suitable locations for background atmospheric monitoring station. Detailed methods for evaluating some of these criteria are also provided and a case study for establishment ofmore » an atmospheric background surveillance station as part of an environmental surveillance program is described. While the case study focuses on monitoring for radionuclides, the approach is equally valid for any airborne constituent being monitored. The case study shows that implementation of the developed criteria can result in a good, defensible choice for a background atmospheric monitoring location.« less

Plant cell technologies in space: Background, strategies and prospects

NASA Technical Reports Server (NTRS)

Kirkorian, A. D.; Scheld, H. W.

1987-01-01

An attempt is made to summarize work in plant cell technologies in space. The evolution of concepts and the general principles of plant tissue culture are discussed. The potential for production of high value secondary products by plant cells and differentiated tissue in automated, precisely controlled bioreactors is discussed. The general course of the development of the literature on plant tissue culture is highlighted.

Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death induction upon temozolomide and quercetin treatment

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

Jakubowicz-Gil, Joanna, E-mail: jjgil@poczta.umcs.lublin.pl; Langner, Ewa; Bądziul, Dorota

The aim of the present study was to investigate whether silencing of Hsp27 or Hsp72 expression in glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cells increases their sensitivity to programmed cell death induction upon temozolomide and/or quercetin treatment. Transfection with specific siRNA was performed for the Hsp gene silencing. As revealed by microscopic observation and flow cytometry, the inhibition of Hsp expression was correlated with severe apoptosis induction upon the drug treatment studied. No signs of autophagy were detected. This was correlated with a decreased mitochondrial membrane potential, increased level of cytochrome c in the cytoplasm, and activation of caspasemore » 3 and caspase 9. All these results suggest that the apoptotic signal was mediated by an internal pathway. Additionally, in a large percentage of cells treated with temozolomide, with or without quercetin, granules within the ER system were found, which was accompanied by an increased level of caspase 12 expression. This might be correlated with ER stress. Quercetin and temozolomide also changed the shape of nuclei from circular to “croissant like” in both transfected cell lines. Our results indicate that blocking of Hsp27 and Hsp72 expression makes T98G cells and MOGGCCM cells extremely vulnerable to apoptosis induction upon temozolomide and quercetin treatment and that programmed cell death is initiated by an internal signal. - Highlights: • Hsps gene silencing induced severe apoptosis upon temozolomide–quercetin treatment • Apoptosis in transfected glioma cells was initiated by internal signal • Programmed cell death was preceded by ER stress • Temozolomide–quercetin treatment changed nuclei shape in transfected glioma cells.« less

[Maintenance treatment in opioid-dependent patients with migration background].

PubMed

Bald, L K; Schouler-Ocak, M; Penka, S; Schoofs, N; Häbel, T; Bermpohl, F; Gutwinski, S

2016-05-01

No regional analyses regarding opioid-dependent patients in maintenance treatment with a migration background have so far been performed in German-speaking countries. This study examined patients with and without a migration background regarding socioeconomic parameters, characteristics of dependency and attitude towards opiate maintenance treatment (OMT). From May to October 2011 patients in OMT from all of the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to provide OMT were included in this analysis. Out of the 986 participating patients, 956 gave information on migration background and of these, 204 (21.3 %) originated from a country other than Germany. Compared to patients without a migration background, their participation in a maintenance program was significantly shorter and they more often expressed a desire to end OMT and wanted a limited duration of OMT. The differences regarding duration of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a different attitude towards maintenance treatment of patients with a migration background.

Apoptosis in fish: environmental factors and programmed cell death.

PubMed

AnvariFar, Hossein; Amirkolaie, Abdolsamad Keramat; Miandare, Hamed Kolangi; Ouraji, Hossein; Jalali, M Ali; Üçüncü, Sema İşisağ

2017-06-01

Apoptosis, a form of programmed cell death, is a critical component in maintaining homeostasis and growth in all tissues and plays a significant role in immunity and cytotoxicity. In contrast to necrosis or traumatic cell death, apoptosis is a well-controlled and vital process characterized mainly by cytoplasmic shrinkage, chromatin condensation, DNA fragmentation, membrane blebbing and apoptotic bodies. Our understanding of apoptosis is partly based on observations in invertebrates but mainly in mammals. Despite the great advantages of fish models in studying vertebrate development and diseases and the tremendous interest observed in recent years, reports on apoptosis in fish are still limited. Although apoptotic machinery is well conserved between aquatic and terrestrial organisms throughout the history of evolution, some differences exist in key components of apoptotic pathways. Core parts of apoptotic machinery in fish are virtually expressed as equivalent to the mammalian models. Some differences are, however, evident, such as the extrinsic and intrinsic pathways of apoptosis including lack of a C-terminal region in the Fas-associated protein with a death domain in fish. Aquatic species inhabit a complex and highly fluctuating environment, making these species good examples to reveal features of apoptosis that may not be easily investigated in mammals. Therefore, in order to gain a wider view on programmed cell death in fish, interactions between the main environmental factors, chemicals and apoptosis are discussed in this review. It is indicated that apoptosis can be induced in fish by exposure to environmental stressors during different stages of the fish life cycle.

Community engagement to inform the development of a sickle cell counselor training and certification program in Ghana.

PubMed

Anie, Kofi A; Treadwell, Marsha J; Grant, Althea M; Dennis-Antwi, Jemima A; Asafo, Mabel K; Lamptey, Mary E; Ojodu, Jelili; Yusuf, Careema; Otaigbe, Ayo; Ohene-Frempong, Kwaku

2016-07-01

Sickle cell disease (SCD) and sickle cell trait (SCT) are highly prevalent in Africa. Despite public health implications, there is limited understanding of community issues for implementing newborn screening and appropriate family counseling. We conducted a 3-day workshop in Kumasi, Ghana, with community leaders as lay program development advisors to assist the development and implementation of a Sickle Cell Counselor Training and Certification Program. We employed qualitative methods to understand cultural, religious, and psychosocial dimensions of SCD and SCT, including the advisors' attitudes and beliefs in relation to developing a culturally sensitive approach to family education and counseling that is maximally suited to diverse communities in Ghana. We collated advisors' discussions and observations in order to understand community issues and potential challenges and guide strategies for advocacy in SCD family education and counseling. Results from the workshop revealed that community leaders representing diverse communities in Ghana were engaged constructively in discussions about developing a culturally sensitive counselor training program. Key findings included the importance of improved knowledge about SCD among the public and youth in particular, the value of stakeholders such as elders and religious and traditional leaders, and government expectations of reduced SCD births. We submitted a report to the Ministry of Health in Ghana with recommendations for the next steps in developing a national sickle cell counselor training program. We named the program "Genetic Education and Counseling for Sickle Cell Conditions in Ghana" (GENECIS-Ghana). The first GENECIS-Ghana Training and Certification Program Workshop was conducted from June 8 to 12, 2015.

A lysigenic programmed cell death-dependent process shapes schizogenously formed aerenchyma in the stems of the waterweed Egeria densa

PubMed Central

Bartoli, G.; Forino, L. M. C.; Durante, M.; Tagliasacchi, A. M.

2015-01-01

Background and Aims Plant adaptation to submergence can include the formation of prominent aerenchyma to facilitate gas exchange. The aim of this study was to characterize the differentiation of the constitutive aerenchyma in the stem of the aquatic macrophyte Egeria densa (Hydrocharitaceae) and to verify if any form of cell death might be involved. Methods Plants were collected from a pool in a botanical garden. Aerenchyma differentiation and apoptotic hallmarks were investigated by light microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay coupled with genomic DNA extraction and gel electrophoresis (DNA laddering assay). Cell viability and the occurrence of peroxides and nitric oxide (NO) were determined histochemically using specific fluorogenic probes. Key Results Aerenchyma differentiation started from a hexagonally packed pre-aerenchymatic tissue and, following a basipetal and centripetal developmental pattern, produced a honeycomb arrangement. After an early schizogenous differentiation process, a late lysigenous programmed cell death- (PCD) dependent mechanism occurred. This was characterized by a number of typical apoptotic hallmarks, including DNA fragmentation, chromatin condensation, apoptotic-like bodies, partial cell wall lysis and plasmolysis. In addition, local increases in H2O2 and NO were observed and quantified. Conclusions The differentiation of cortical aerenchyma in the stem of E. densa is a complex process, consisting of a combination of an early schizogenous differentiation mechanism and a late lysigenous PCD-dependent process. The PCD remodels the architecture of the gas spaces previously formed schizogenously, and also results in a reduction of O2-consuming cells and in recycling of material derived from the lysigenic dismantling of the cells. PMID:26002256

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program

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

none,

This FY 2011 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

DTIC Science & Technology

2015-12-17

AP funding for the ship. Oversight issues for Congress for the CVN-78 program include the following:  the potential impact on the CVN-78 program...Potential Impact of Continuing Resolution (CR) for FY2016 .................................................. 7 Overview...7 Impact on CVN-78 Program

Results of the 2000 JPL Balloon Flight Solar Cell Calibration Program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Mueller, R. L.; Weiss, R. S.

2001-01-01

The 2000 solar cell calibration balloon flight campaign consisted of two flights, which occurred on June 27, 2000, and July 5, 2000. All objectives of the flight program were met. Sixty-two modules were carried to an altitude of approximately 120,000 ft (36.6 km). Full I-V curves were measured on sixteen of these modules, and output at a fixed load was measured on thirty-seven modules (forty-six cells), with some modules repeated on the second flight. Nine modules were flown for temperature measurement only. This data was corrected to 28 C and to 1 AU (1.496x10(exp 8) km). The calibrated cells have been returned to their owners and can now be used as reference standards in simulator testing of cells and arrays.

Regenerative Fuel Cell System Testbed Program for Government and Commercial Applications

NASA Technical Reports Server (NTRS)

1996-01-01

NASA Lewis Research Center's Electrochemical Technology Branch has led a multiagency effort to design, fabricate, and operate a regenerative fuel cell (RFC) system testbed. Key objectives of this program are to evaluate, characterize, and demonstrate fully integrated RFC's for space, military, and commercial applications. The Lewis-led team is implementing the program through a unique international coalition that encompasses both Government and industry participants. Construction of the 25-kW RFC testbed at the NASA facility at Edwards Air Force Base was completed in January 1995, and the system has been operational since that time.

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells.

PubMed

Reyes-Reyes, Elsa M; Aispuro, Ivan; Tavera-Garcia, Marco A; Field, Matthew; Moore, Sara; Ramos, Irma; Ramos, Kenneth S

2017-11-28

Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo . These findings identify a TGFβ1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

Sulfated lentinan induced mitochondrial dysfunction leads to programmed cell death of tobacco BY-2 cells.

PubMed

Wang, Jie; Wang, Yaofeng; Shen, Lili; Qian, Yumei; Yang, Jinguang; Wang, Fenglong

2017-04-01

Sulphated lentinan (sLTN) is known to act as a resistance inducer by causing programmed cell death (PCD) in tobacco suspension cells. However, the underlying mechanism of this effect is largely unknown. Using tobacco BY-2 cell model, morphological and biochemical studies revealed that mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction contribute to sLNT induced PCD. Cell viability, and HO/PI fluorescence imaging and TUNEL assays confirmed a typical cell death process caused by sLNT. Acetylsalicylic acid (an ROS scavenger), diphenylene iodonium (an inhibitor of NADPH oxidases) and protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (a protonophore and an uncoupler of mitochondrial oxidative phosphorylation) inhibited sLNT-induced H 2 O 2 generation and cell death, suggesting that ROS generation linked, at least partly, to a mitochondrial dysfunction and caspase-like activation. This conclusion was further confirmed by double-stained cells with the mitochondria-specific marker MitoTracker RedCMXRos and the ROS probe H 2 DCFDA. Moreover, the sLNT-induced PCD of BY-2 cells required cellular metabolism as up-regulation of the AOX family gene transcripts and induction of the SA biosynthesis, the TCA cycle, and miETC related genes were observed. It is concluded that mitochondria play an essential role in the signaling pathway of sLNT-induced ROS generation, which possibly provided new insight into the sLNT-mediated antiviral response, including PCD. Copyright © 2016. Published by Elsevier Inc.

Results of the 1996 JPL Balloon Flight Solar Cell Calibration Program

NASA Technical Reports Server (NTRS)

Anspaugh, B. E.; Weiss, R. S.

1996-01-01

The 1996 solar cell calibration balloon flight campaign was completed with the first flight on June 30, 1996 and a second flight on August 8, 1996. All objectives of the flight program were met. Sixty-four modules were carried to an altitude of 120,000 ft (36.6 km). Full 1-5 curves were measured on 22 of these modules, and output at a fixed load was measured on 42 modules. This data was corrected to 28 C and to 1 AU (1.496 x 10(exp 8) km). The calibrated cells have been returned to the participants and can now be used as reference standards in simulator testing of cells and arrays.

Evidence for a stepwise program of extrathymic T cell development within the human tonsil

PubMed Central

McClory, Susan; Hughes, Tiffany; Freud, Aharon G.; Briercheck, Edward L.; Martin, Chelsea; Trimboli, Anthony J.; Yu, Jianhua; Zhang, Xiaoli; Leone, Gustavo; Nuovo, Gerard; Caligiuri, Michael A.

2012-01-01

The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin– cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34+CD38brightLin– cells; (c) CD34+CD1a+CD11c– cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34–CD1a+CD3–CD11c– cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e) CD34–CD1a+CD3+CD11c– cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre–T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development. PMID:22378041

Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption in Malignancy.

PubMed

Mukherjee, Subhas; Brat, Daniel J

2017-01-01

Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two unequal daughter cells. One retains its stem cell identity while the other becomes specialized through a differentiation program and loses stem cell properties. Coordinating these events requires control over numerous intra- and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell in order to direct their destiny. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and non-canonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.

Re-programming tumour cell metabolism to treat cancer: no lone target for lonidamine.

PubMed

Bhutia, Yangzom D; Babu, Ellappan; Ganapathy, Vadivel

2016-06-01

Tumour cell metabolism is very different from normal cell metabolism; cancer cells re-programme the metabolic pathways that occur in normal cells in such a manner that it optimizes their proliferation, growth and survival. Although this metabolic re-programming obviously operates to the advantage of the tumour, it also offers unique opportunities for effective cancer therapy. Molecules that target the tumour cell-specific metabolic pathways have potential as novel anti-cancer drugs. Lonidamine belongs to this group of molecules and is already in use in some countries for cancer treatment. It has been known for a long time that lonidamine interferes with energy production in tumour cells by inhibiting hexokinase II (HKII), a glycolytic enzyme. However, subsequent studies have uncovered additional pharmacological targets for the drug, which include the electron transport chain and the mitochondrial permeability transition pore, thus expanding the pharmacological effects of the drug on tumour cell metabolism. A study by Nancolas et al. in a recent issue of the Biochemical Journal identifies two additional new targets for lonidamine: the pyruvate transporter in the mitochondria and the H(+)-coupled monocarboxylate transporters in the plasma membrane (PM). It is thus becoming increasingly apparent that the anti-cancer effects of lonidamine do not occur through a single target; the drug works at multiple sites. Irrespective of the molecular targets, what lonidamine does in the end is to undo what the tumour cells have done in terms of re-programming cellular metabolism and mitochondrial function. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Assessment of the environmental aspects of the DOE phosphoric acid fuel cell program

NASA Technical Reports Server (NTRS)

Lundblad, H. L.; Cavagrotti, R. R.

1983-01-01

The likely facets of a nationwide phosphoric acid fuel cell (PAFC) power plant commercial system are described. The beneficial and adverse environmental impacts produced by the system are assessed. Eleven specific system activities are characterized and evaluated. Also included is a review of fuel cell technology and a description of DOE's National Fuel Cell Program. Based on current and reasonably foreseeable PAFC characteristics, no environmental or energy impact factor was identified that would significantly inhibit the commercialization of PAFC power plant technology.

Appendix C: Background and Methodology for Alternative Certification Pilot. [2014 Teacher Prep Review

ERIC Educational Resources Information Center

Greenberg, Julie; Walsh, Kate; McKee, Arthur

2014-01-01

The "NCTQ Teacher Prep Review" evaluates the quality of programs that provide preservice preparation of public school teachers. As part of the "Review," this appendix reports on a pilot study of new standards for assessing the quality of alternative certification programs. Background and methodology for alternative…

Innovative Training in Pediatrics, General Psychiatry, and Child Psychiatry: Background, Outcomes, and Experiences

ERIC Educational Resources Information Center

Gleason, Mary Margaret; Fritz, Gregory K.

2009-01-01

Objectives: The authors describe the history, rationale, and outcomes of combined training programs in pediatrics, psychiatry, and child psychiatry ("triple board"), including narrative feedback from graduates and reflections upon the important components of the program. Methods: This article reviews the background and experiences of triple board…

Using Background Music To Enhance Memory and Improve Learning.

ERIC Educational Resources Information Center

Anderson, Scheree; Henke, Jeanette; McLaughlin, Maureen; Ripp, Mary; Tuffs, Patricia

This report describes a program to enhance spelling word retention through the use of background music. The targeted population consisted of elementary students in three middle class communities located in the southwestern suburbs of Chicago. The problems for poor spelling retention were documented through data revealing the number of students…

Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites.

PubMed

Kaczanowski, Szymon; Sajid, Mohammed; Reece, Sarah E

2011-03-25

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities.

Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites

PubMed Central

2011-01-01

Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania. Apoptosis-like PCD in protozoan parasites shares a number of morphological features with programmed cell death in multicellular organisms. However, both the evolutionary explanations and mechanisms involved in parasite PCD are poorly understood. Explaining why unicellular organisms appear to undergo 'suicide' is a challenge for evolutionary biology and uncovering death executors and pathways is a challenge for molecular and cell biology. Bioinformatics has the potential to integrate these approaches by revealing homologies in the PCD machinery of diverse taxa and evaluating their evolutionary trajectories. As the molecular mechanisms of apoptosis in model organisms are well characterised, and recent data suggest similar mechanisms operate in protozoan parasites, key questions can now be addressed. These questions include: which elements of apoptosis machinery appear to be shared between protozoan parasites and multicellular taxa and, have these mechanisms arisen through convergent or divergent evolution? We use bioinformatics to address these questions and our analyses suggest that apoptosis mechanisms in protozoan parasites and other taxa have diverged during their evolution, that some apoptosis factors are shared across taxa whilst others have been replaced by proteins with similar biochemical activities. PMID:21439063

Glutathione Decrement Drives Thermogenic Program In Adipose Cells.

PubMed

Lettieri Barbato, Daniele; Tatulli, Giuseppe; Maria Cannata, Stefano; Bernardini, Sergio; Aquilano, Katia; Ciriolo, Maria R

2015-08-11

Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the "browning" effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes.

Glutathione Decrement Drives Thermogenic Program In Adipose Cells

PubMed Central

Lettieri Barbato, Daniele; Tatulli, Giuseppe; Maria Cannata, Stefano; Bernardini, Sergio; Aquilano, Katia; Ciriolo, Maria R.

2015-01-01

Adipose tissue metabolically adapts to external stimuli. We demonstrate that the induction of the thermogenic program in white adipocytes, through cold exposure in mice or in vitro adrenergic stimulation, is accompanied by a decrease in the intracellular content of glutathione (GSH). Moreover, the treatment with a GSH depleting agent, buthionine sulfoximine (BSO), recapitulates the effect of cold exposure resulting in the induction of thermogenic program. In particular, BSO treatment leads to enhanced uncoupling respiration as demonstrated by increased expression of thermogenic genes (e.g. Ucp1, Ppargc1a), augmented oxygen consumption and decreased mitochondrial transmembrane potential. Buffering GSH decrement by pre-treatment with GSH ester prevents the up-regulation of typical markers of uncoupling respiration. We demonstrate that FoxO1 activation is responsible for the conversion of white adipocytes into a brown phenotype as the “browning” effects of BSO are completely abrogated in cells down-regulating FoxO1. In mice, the BSO-mediated up-regulation of uncoupling genes results in weight loss that is at least in part ascribed to adipose tissue mass reduction. The induction of thermogenic program has been largely proposed to counteract obesity-related diseases. Based on these findings, we propose GSH as a novel therapeutic target to increase energy expenditure in adipocytes. PMID:26260892

The National School Lunch Program: Background, Trends, and Issues. ERS Report Summary

ERIC Educational Resources Information Center

Ralston, Katherine; Newman, Constance; Clauson, Annette; Guthrie, Joanne; Buzby, Jean

2008-01-01

The National School Lunch Program (NSLP) is one of the largest food and nutrition assistance programs in the United States, feeding millions of children every day. School meal providers face the task of serving nutritious and appealing school lunches, including free and reduced-price lunches for low-income students, and doing so under budget…

Opening minds in Canada: background and rationale.

PubMed

Stuart, Heather; Chen, Shu-Ping; Christie, Romie; Dobson, Keith; Kirsh, Bonnie; Knaak, Stephanie; Koller, Michelle; Krupa, Terry; Lauria-Horner, Bianca; Luong, Dorothy; Modgill, Geeta; Patten, Scott B; Pietrus, Mike; Szeto, Andrew; Whitley, Rob

2014-10-01

To summarize the background and rationale of the approach taken by the Mental Health Commission of Canada's Opening Minds (OM) Anti-Stigma Initiative. The approach taken by OM incorporates a grassroots, community development philosophy, has clearly defined target groups, uses contact-based education as the central organizing element across interventions, and has a strong evaluative component, so that best practices can be identified, replicated, and disseminated. Contact-based education occurs when people who have experienced a mental illness share their personal story of recovery and hope. OM has acted as a catalyst to develop partnerships between community groups who are undertaking anti-stigma work and an interdisciplinary team of academic researchers in 5 universities who are evaluating the results of these programs. Building partnerships with existing community programs and promoting systematic evaluation using standardized approaches and instruments have contributed to our understanding of best practices in the field of anti-stigma programming.

Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.

PubMed

Rodriguez, Ramon M; Suarez-Alvarez, Beatriz; Lavín, José L; Mosén-Ansorena, David; Baragaño Raneros, Aroa; Márquez-Kisinousky, Leonardo; Aransay, Ana M; Lopez-Larrea, Carlos

2017-01-15

Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8 + T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8 + T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8 + T cell maintenance and T cell terminal differentiation. Copyright © 2017 by The American Association of Immunologists, Inc.

Planning Lessons for Refugee-Background Students: Challenges and Strategies

ERIC Educational Resources Information Center

Miller, Jennifer; Windle, Joel Austin; Yazdanpanah, Lilly K.

2014-01-01

This article examines the ways teachers plan lessons for English as an Additional Language (EAL) students from refugee backgrounds in secondary school transition programs. Based on a study of teachers working with students in three Victorian schools, we identify the key challenges teachers face in planning and the strategies they adopt to confront…

Evaluation program for secondary spacecraft cells: Acceptance test of Eagle-Picher 100 ampere-hour nickel-cadmium cells with auxiliary electrodes

NASA Technical Reports Server (NTRS)

Christy, D. E.

1972-01-01

Tests were conducted on a group of 29 cells for the purpose of removing from the life cycle program all cells found to have electrolyte leakage, internal shorts, low capacity, or inability to recover open circuit voltage above 1.150 volts after the cell short test. The test findings include the following: (1) All the cells exceeded the rated capacity of 103.5 to 119.0 ampere-hours on all three capacity checks. (2) All cells recovered above the 1.150 volt requirement after the cell short test. (3) The cells cannot be overcharged at the c/10 rate without exceeding 1.500 volts after approximately 12 to 13 hours of charge. (4) The resistance value necessary to provide maximum signal power across the auxiliary electrode was found to be 10 ohms. (5) One cell revealed a definite leak at the negative terminal.

Student Financing in the Health Professions: Dependence on and Interactions between the Higher Education Act and the Public Health Service Act Financial Aid Programs: A Background Paper. Draft.

ERIC Educational Resources Information Center

Advisory Committee on Student Financial Assistance, Washington, DC.

This paper identifies issues that underlie student financing of education in the health professions in terms of the interrelationships and interactions between financial aid programs under Title IV of the Higher Education Act and Titles VII and VIII of the Public Health Service Act. Section 1 provides background to the issues by describing…

Organ damage mitigation with the Baskent Sickle Cell Medical Care Development Program (BASCARE)

PubMed Central

Ozdogu, Hakan; Boga, Can; Asma, Suheyl; Kozanoglu, Ilknur; Gereklioglu, Cigdem; Yeral, Mahmut; Buyukkurt, Nurhilal Turgut; Solmaz, Soner; Korur, Aslı; Aytan, Pelin; Maytalman, Erkan; Kasar, Mutlu

2018-01-01

Abstract The Eastern Mediterranean is among the regions where sickle cell disease (SCD) is common. The morbidity and mortality of this disease can be postponed to adulthood through therapies implemented in childhood. The present study focuses on the organ damage-reducing effects of the Baskent Sickle Cell Medical Care Development Program (BASCARE), which was developed by a team who lives in this region and has approximately 25 years of experience. The deliverables of the program included the development of an electronic health recording system (PRANA) and electronic vaccination system; the use of low citrate infusion in routine prophylactic automatic erythrocyte exchange (ARCE) programs including pregnant women; the use of leukocyte-filtered and irradiated blood for transfusion; the use of magnetic resonance imaging methods (T2∗) for the management of transfusion-related hemosiderosis; and the implementation of an allogeneic hematopoietic stem cell transplantation protocol for adult patients. The sample was composed of 376 study subjects and 249 control subjects. The hospital's Data Management System and the central population operating system were used for data collection. BASCARE enabled better analysis and interpretation of complication and mortality data. Vaccination rates against influenza and pneumococcal disease improved (21.5% vs 50.8% and 21.5% vs 49.2%, respectively). Effective and safe ARCE with low citrate infusion were maintained in 352 subjects (1003 procedures). Maternal and fetal mortality was prevented in 35 consecutive pregnant patients with ARCE. Chelating therapy rates reduced from 6.7% to 5%. Successful outcomes could be obtained in all 13 adult patients who underwent allogeneic peripheral stem cell transplantation from a fully matched, related donor. No patients died by day 100 or after the first year. Cure could be achieved without graft loss, grades III to IV acute graft versus host disease, extensive chronic graft versus host disease, or

Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

NASA Technical Reports Server (NTRS)

Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

2017-01-01

Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

Authorized Course of Instruction for the Quinmester Program. Science: Cell Biology, Introduction to Life Science.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

This instructional package contains two biological units developed for the Dade County Florida Quinmester Program. "Introduction to Life Sciences" develops student understandings of cell structure and function, and compares different levels of cellular organization. "Cell Biology" investigates the origin of modern cellular…

Fuel Cell Development for NASA's Human Exploration Program: Benchmarking with "The Hydrogen Economy"

NASA Technical Reports Server (NTRS)

Scott, John H.

2007-01-01

The theoretically high efficiency and low temperature operation of hydrogen-oxygen fuel cells has motivated them to be the subject of much study since their invention in the 19th Century, but their relatively high life cycle costs kept them as a "solution in search of a problem" for many years. The first problem for which fuel cells presented a truly cost effective solution was that of providing a power source for NASA's human spaceflight vehicles in the 1960 s. NASA thus invested, and continues to invest, in the development of fuel cell power plants for this application. This development program continues to place its highest priorities on requirements for minimum system mass and maximum durability and reliability. These priorities drive fuel cell power plant design decisions at all levels, even that of catalyst support. However, since the mid-1990's, prospective environmental regulations have driven increased governmental and industrial interest in "green power" and the "Hydrogen Economy." This has in turn stimulated greatly increased investment in fuel cell development for a variety of commercial applications. This investment is bringing about notable advances in fuel cell technology, but, as these development efforts place their highest priority on requirements for minimum life cycle cost and field safety, these advances are yielding design solutions quite different at almost every level from those needed for spacecraft applications. This environment thus presents both opportunities and challenges for NASA's Human Exploration Program

A Common Programming Language for the Department of Defense--Background and Technical Requirements

DTIC Science & Technology

1976-06-01

Method Findings I. Introduction A. The Problem 1. Software Costs 2. Programming Language 3. Lack of Comrr.onality 4. Common Language 5...accessible soft- ware tools and aids. There are a number of widely held perceptions about the ill effects of the lack of programming language ...cost- effective (at lea~t during development) than de- velopi~g a new programming language specialized to the project. On the other hand,

Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 12.0 ampere-hour nickel-cadmium spacecraft cells for the international ultraviolet explorer

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1976-01-01

An evaluation test program was conducted to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. The 20 cells were manufactured for the National Aeronautics and Space Administration, Goddard Space Flight Center (GSFC). The cells are from a lot of 175 cells procured for the International Ultraviolet Explorer project. Due to a change in requirements, the project selected to use 6.0 ampere-hour cells. Therefore, the remaining cells of this lot have been placed in storage at GSFC for use on a future GSFC project. All the cells are rated at 12.0 ampere-hours and contain double ceramic seals. Test limits specify those values in which a cell is to be terminated from a particular charge or discharge. Requirements are referred to as normally expected values based on past performance of aerospace nickel cadmium cells with demonstrated life characteristics.

An extensive program of periodic alternative splicing linked to cell cycle progression

PubMed Central

Dominguez, Daniel; Tsai, Yi-Hsuan; Weatheritt, Robert; Wang, Yang; Blencowe, Benjamin J; Wang, Zefeng

2016-01-01

Progression through the mitotic cell cycle requires periodic regulation of gene function at the levels of transcription, translation, protein-protein interactions, post-translational modification and degradation. However, the role of alternative splicing (AS) in the temporal control of cell cycle is not well understood. By sequencing the human transcriptome through two continuous cell cycles, we identify ~1300 genes with cell cycle-dependent AS changes. These genes are significantly enriched in functions linked to cell cycle control, yet they do not significantly overlap genes subject to periodic changes in steady-state transcript levels. Many of the periodically spliced genes are controlled by the SR protein kinase CLK1, whose level undergoes cell cycle-dependent fluctuations via an auto-inhibitory circuit. Disruption of CLK1 causes pleiotropic cell cycle defects and loss of proliferation, whereas CLK1 over-expression is associated with various cancers. These results thus reveal a large program of CLK1-regulated periodic AS intimately associated with cell cycle control. DOI: http://dx.doi.org/10.7554/eLife.10288.001 PMID:27015110

Vacuolar processing enzyme in plant programmed cell death

PubMed Central

Hatsugai, Noriyuki; Yamada, Kenji; Goto-Yamada, Shino; Hara-Nishimura, Ikuko

2015-01-01

Vacuolar processing enzyme (VPE) is a cysteine proteinase originally identified as the proteinase responsible for the maturation and activation of vacuolar proteins in plants, and it is known to be an ortholog of animal asparaginyl endopeptidase (AEP/VPE/legumain). VPE has been shown to exhibit enzymatic properties similar to that of caspase 1, which is a cysteine protease that mediates the programmed cell death (PCD) pathway in animals. Although there is limited sequence identity between VPE and caspase 1, their predicted three-dimensional structures revealed that the essential amino-acid residues for these enzymes form similar pockets for the substrate peptide YVAD. In contrast to the cytosolic localization of caspases, VPE is localized in vacuoles. VPE provokes vacuolar rupture, initiating the proteolytic cascade leading to PCD in the plant immune response. It has become apparent that the VPE-dependent PCD pathway is involved not only in the immune response, but also in the responses to a variety of stress inducers and in the development of various tissues. This review summarizes the current knowledge on the contribution of VPE to plant PCD and its role in vacuole-mediated cell death, and it also compares VPE with the animal cell death executor caspase 1. PMID:25914711

Coast Guard Deepwater Acquisition Programs: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-12-23

NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Congressional Research Service,Library of Congress...Northrop Grumman Ship Systems ( NGSS ). ICGS was awarded an indefinite delivery, indefinite quantity (ID/IQ) contract for the Deepwater program that...sustainment is not a Deepwater program but is displayed to align with the FY2009 Consolidated Security, Disaster Assistance, and Continuing Appropriations

Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response

PubMed Central

Rui, Yuxiang; Honjo, Tasuku; Chikuma, Shunsuke

2013-01-01

Programmed cell death 1 (PD-1) is an inhibitory coreceptor on immune cells and is essential for self-tolerance because mice genetically lacking PD-1 (PD-1−/−) develop spontaneous autoimmune diseases. PD-1−/− mice are also susceptible to severe experimental autoimmune encephalomyelitis (EAE), characterized by a massive production of effector/memory T cells against myelin autoantigen, the mechanism of which is not fully understood. We found that an increased primary response of PD-1−/− mice to heat-killed mycobacteria (HKMTB), an adjuvant for EAE, contributed to the enhanced production of T-helper 17 (Th17) cells. Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1−/− recombination activating gene (RAG)2−/− mice were found to drive antigen-specific Th17 cell differentiation more efficiently than splenocytes from HKMTB-immunized PD-1+/+ RAG2−/− mice. This result suggested PD-1’s involvement in the regulation of innate immune responses. Mice reconstituted with PD-1−/− RAG2−/− bone marrow and PD-1+/+ CD4+ T cells developed more severe EAE compared with the ones reconstituted with PD-1+/+ RAG2−/− bone marrow and PD-1+/+ CD4+ T cells. We found that upon recognition of HKMTB, CD11b+ macrophages from PD-1−/− mice produced very high levels of IL-6, which helped promote naive CD4+ T-cell differentiation into IL-17–producing cells. We propose a model in which PD-1 negatively regulates antimycobacterial responses by suppressing innate immune cells, which in turn prevents autoreactive T-cell priming and differentiation to inflammatory effector T cells. PMID:24043779

Evaluation program for secondary spacecraft cells: Initial evaluation tests of Eagel-Picher Industries, Incorporated, 20.0 amphere-hour nickel-cadmium spacecraft cells

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1974-01-01

An evaluation test of the 20.0 ampere-hour cells was conducted to insure that all cells put into the life cycle program are of high quality. This is accomplished by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test. The results obtained in the test are given, as well as the recommendations based on these findings.

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program - 2012

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

none,

This FY 2012 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Segmentation of whole cells and cell nuclei from 3-D optical microscope images using dynamic programming.

PubMed

McCullough, D P; Gudla, P R; Harris, B S; Collins, J A; Meaburn, K J; Nakaya, M A; Yamaguchi, T P; Misteli, T; Lockett, S J

2008-05-01

Communications between cells in large part drive tissue development and function, as well as disease-related processes such as tumorigenesis. Understanding the mechanistic bases of these processes necessitates quantifying specific molecules in adjacent cells or cell nuclei of intact tissue. However, a major restriction on such analyses is the lack of an efficient method that correctly segments each object (cell or nucleus) from 3-D images of an intact tissue specimen. We report a highly reliable and accurate semi-automatic algorithmic method for segmenting fluorescence-labeled cells or nuclei from 3-D tissue images. Segmentation begins with semi-automatic, 2-D object delineation in a user-selected plane, using dynamic programming (DP) to locate the border with an accumulated intensity per unit length greater that any other possible border around the same object. Then the two surfaces of the object in planes above and below the selected plane are found using an algorithm that combines DP and combinatorial searching. Following segmentation, any perceived errors can be interactively corrected. Segmentation accuracy is not significantly affected by intermittent labeling of object surfaces, diffuse surfaces, or spurious signals away from surfaces. The unique strength of the segmentation method was demonstrated on a variety of biological tissue samples where all cells, including irregularly shaped cells, were accurately segmented based on visual inspection.

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2008-11-18

ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES... Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary Roughead, the Chief of Naval Operations, as...the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile development programs. A 2005 defense trade press report

Background Characterization Techniques For Pattern Recognition Applications

NASA Astrophysics Data System (ADS)

Noah, Meg A.; Noah, Paul V.; Schroeder, John W.; Kessler, Bernard V.; Chernick, Julian A.

1989-08-01

The Department of Defense has a requirement to investigate technologies for the detection of air and ground vehicles in a clutter environment. The use of autonomous systems using infrared, visible, and millimeter wave detectors has the potential to meet DOD's needs. In general, however, the hard-ware technology (large detector arrays with high sensitivity) has outpaced the development of processing techniques and software. In a complex background scene the "problem" is as much one of clutter rejection as it is target detection. The work described in this paper has investigated a new, and innovative, methodology for background clutter characterization, target detection and target identification. The approach uses multivariate statistical analysis to evaluate a set of image metrics applied to infrared cloud imagery and terrain clutter scenes. The techniques are applied to two distinct problems: the characterization of atmospheric water vapor cloud scenes for the Navy's Infrared Search and Track (IRST) applications to support the Infrared Modeling Measurement and Analysis Program (IRAMMP); and the detection of ground vehicles for the Army's Autonomous Homing Munitions (AHM) problems. This work was sponsored under two separate Small Business Innovative Research (SBIR) programs by the Naval Surface Warfare Center (NSWC), White Oak MD, and the Army Material Systems Analysis Activity at Aberdeen Proving Ground MD. The software described in this paper will be available from the respective contract technical representatives.

Manual of phosphoric acid fuel cell stack three-dimensional model and computer program

NASA Technical Reports Server (NTRS)

Lu, C. Y.; Alkasab, K. A.

1984-01-01

A detailed distributed mathematical model of phosphoric acid fuel cell stack have been developed, with the FORTRAN computer program, for analyzing the temperature distribution in the stack and the associated current density distribution on the cell plates. Energy, mass, and electrochemical analyses in the stack were combined to develop the model. Several reasonable assumptions were made to solve this mathematical model by means of the finite differences numerical method.

Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis.

PubMed

Wang, Fei; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Hutchins, Noelle A; Ayala, Alfred

2016-08-01

Recent studies suggest that coinhibitory receptors appear to be important in contributing sepsis-induced immunosuppression. Our laboratory reported that mice deficient in programmed cell death receptor (PD)-1 have increased bacterial clearance and improved survival in experimental sepsis induced by cecal ligation and puncture (CLP). In response to infection, the liver clears the blood of bacteria and produces cytokines. Kupffer cells, the resident macrophages in the liver, are strategically situated to perform the above functions. However, it is not known if PD-1 expression on Kupffer cells is altered by septic stimuli, let alone if PD-1 ligation contributes to the altered microbial handling seen. Here we report that PD-1 is significantly upregulated on Kupffer cells during sepsis. PD-1-deficient septic mouse Kupffer cells displayed markedly enhanced phagocytosis and restoration of the expression of major histocompatibility complex II and CD86, but reduced CD80 expression compared with septic wild-type (WT) mouse Kupffer cells. In response to ex vivo LPS stimulation, the cytokine productive capacity of Kupffer cells derived from PD-1-/- CLP mice exhibited a marked, albeit partial, restoration of the release of IL-6, IL-12, IL-1β, monocyte chemoattractant protein-1, and IL-10 compared with septic WT mouse Kupffer cells. In addition, PD-1 gene deficiency decreased LPS-induced apoptosis of septic Kupffer cells, as indicated by decreased levels of cleaved caspase-3 and reduced terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. Exploring the signal pathways involved, we found that, after ex vivo LPS stimulation, septic PD-1-/- mouse Kupffer cells exhibited an increased Akt phosphorylation and a reduced p38 phosphorylation compared with septic WT mouse Kupffer cells. Together, these results indicate that PD-1 appears to play an important role in regulating the development of Kupffer cell dysfunction seen in sepsis. Copyright © 2016 the

Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis

PubMed Central

Wang, Fei; Huang, Xin; Chung, Chun-Shiang; Chen, Yaping; Hutchins, Noelle A.

2016-01-01

Recent studies suggest that coinhibitory receptors appear to be important in contributing sepsis-induced immunosuppression. Our laboratory reported that mice deficient in programmed cell death receptor (PD)-1 have increased bacterial clearance and improved survival in experimental sepsis induced by cecal ligation and puncture (CLP). In response to infection, the liver clears the blood of bacteria and produces cytokines. Kupffer cells, the resident macrophages in the liver, are strategically situated to perform the above functions. However, it is not known if PD-1 expression on Kupffer cells is altered by septic stimuli, let alone if PD-1 ligation contributes to the altered microbial handling seen. Here we report that PD-1 is significantly upregulated on Kupffer cells during sepsis. PD-1-deficient septic mouse Kupffer cells displayed markedly enhanced phagocytosis and restoration of the expression of major histocompatibility complex II and CD86, but reduced CD80 expression compared with septic wild-type (WT) mouse Kupffer cells. In response to ex vivo LPS stimulation, the cytokine productive capacity of Kupffer cells derived from PD-1−/− CLP mice exhibited a marked, albeit partial, restoration of the release of IL-6, IL-12, IL-1β, monocyte chemoattractant protein-1, and IL-10 compared with septic WT mouse Kupffer cells. In addition, PD-1 gene deficiency decreased LPS-induced apoptosis of septic Kupffer cells, as indicated by decreased levels of cleaved caspase-3 and reduced terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. Exploring the signal pathways involved, we found that, after ex vivo LPS stimulation, septic PD-1−/− mouse Kupffer cells exhibited an increased Akt phosphorylation and a reduced p38 phosphorylation compared with septic WT mouse Kupffer cells. Together, these results indicate that PD-1 appears to play an important role in regulating the development of Kupffer cell dysfunction seen in sepsis. PMID:27288425

Effects of the unintentional background concentration, indium composition and defect density on the performance of InGaN p-i-n homojunction solar cells

NASA Astrophysics Data System (ADS)

Wu, Shudong; Cheng, Liwen; Wang, Qiang

2018-07-01

We theoretically investigate the effects of the unintentional background concentration, indium composition and defect density of intrinsic layer (i-layer) on the photovoltaic performance of InGaN p-i-n homojunction solar cells by solving the Poisson and steady-state continuity equations. The built-in electric field and carrier generation rate depend on the position within the i-layer. The collection efficiency, short circuit current density, open circuit voltage, fill factor, and conversion efficiency are found to depend strongly on the background concentration, thickness, indium composition, and defect density of the i-layer. With increasing the background concentration, the maximum thickness of field-bearing i-layer decreases, and the width of depletion region may become even too small to cover the whole i-layer, resulting in a serious decrease of the carrier collection. Some oscillations as a function of indium composition are found in the short circuit current density and conversion efficiency at high indium composition and low defect density due to the interference between the absorbance and the generation rate of carriers. The defect density degrades seriously the overall photovoltaic performance, and its effect on the photovoltaic performance is roughly seven orders of magnitude higher than the previously reported values [Feng et al., J. Appl. Phys. 108 (2010) 093118]. As a result, the high crystalline quality InGaN with high indium composition is a key factor in the device performance of III-nitride based solar cells.

Interactions between genetic background, insulin resistance and β-cell function.

PubMed

Kahn, S E; Suvag, S; Wright, L A; Utzschneider, K M

2012-10-01

An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the β-cell, including the identification of molecules involved in β-cell function that were not previously recognized as playing a role in this critical cell. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

PubMed

Hsu, Peter; Nanan, Ralph

2014-10-01

In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Programmed cell death promotes male sterility in the functional dioecious Opuntia stenopetala (Cactaceae)

PubMed Central

Flores-Rentería, Lluvia; Orozco-Arroyo, Gregorio; Cruz-García, Felipe; García-Campusano, Florencia; Alfaro, Isabel; Vázquez-Santana, Sonia

2013-01-01

Background and Aims The sexual separation in dioecious species has interested biologists for decades; however, the cellular mechanism leading to unisexuality has been poorly understood. In this study, the cellular changes that lead to male sterility in the functionally dioecious cactus, Opuntia stenopetala, are described. Methods The spatial and temporal patterns of programmed cell death (PCD) were determined in the anthers of male and female flowers using scanning electron microscopy analysis and histological observations, focusing attention on the transition from bisexual to unisexual development. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assays were used as an indicator of DNA fragmentation to corroborate PCD. Key results PCD was detected in anthers of both female and male flowers, but their patterns differed in time and space. Functionally male individuals developed viable pollen, and normal development involved PCD on each layer of the anther wall, which occurred progressively from the inner (tapetum) to the outer layer (epidermis). Conversely, functional female individuals aborted anthers by premature and displaced PCD. In anthers of female flowers, the first signs of PCD, such as a nucleus with irregular shape, fragmented and condensed chromatin, high vacuolization and condensed cytoplasm, occurred at the microspore mother cell stage. Later these features were observed simultaneously in all anther wall layers, connective tissue and filament. Neither pollen formation nor anther dehiscence was detected in female flowers of O. stenopetala due to total anther disruption. Conclusions Temporal and spatial changes in the patterns of PCD are responsible for male sterility of female flowers in O. stenopetala. Male fertility requires the co-ordination of different events, which, when altered, can lead to male sterility and to functionally unisexual individuals. PCD could be a widespread mechanism in the determination of

Results of the 1990 NASA/JPL balloon flight solar cell calibration program

NASA Technical Reports Server (NTRS)

Anspaugh, Bruce E.; Weiss, Robert S.

1990-01-01

The 1990 solar cell calibration balloon flight consisted of two flights, one on July 20, 1990 and the other on September 6, 1990. A malfunction occurred during the first flight, which resulted in a complete loss of data and a free fall of the payload from 120,000 ft. After the tracker was rebuilt, and several solar cell modules were replaced, the payload was reflown. The September flight was successful and met all the objectives of the program. Forty-six modules were carried to an altitude of 118,000 ft (36.0 km). Data telemetered from the modules was corrected to 28 C and to 1 a.u. The calibrated cells have been returned to the participants and can now be used as reference standards in simulator testing of cells and arrays.

Integrative Genomic Analyses Yields Cell Cycle Regulatory Programs with Prognostic Value

PubMed Central

Cheng, Chao; Lou, Shaoke; Andrews, Erik H.; Ung, Matthew H.; Varn, Frederick S.

2016-01-01

Liposarcoma is the second most common form of sarcoma, which has been categorized into four molecular subtypes, which are associated with differential prognosis of patients. However, the transcriptional regulatory programs associated with distinct histological and molecular subtypes of liposarcoma have not been investigated. This study uses integrative analyses to systematically define the transcriptional regulatory programs associated with liposarcoma. Likewise, computational methods are used to identify regulatory programs associated with different liposarcoma subtypes as well as programs that are predictive of prognosis. Further analysis of curated gene sets was used to identify prognostic gene signatures. The integration of data from a variety sources including gene expression profiles, transcription factor (TF) binding data from ChIP-seq experiments, curated gene sets, and clinical information of patients indicated discrete regulatory programs (e.g., controlled by E2F1 and E2F4) with significantly different regulatory activity in one or multiple subtypes of liposarcoma with respect to normal adipose tissue. These programs were also shown to be prognostic, wherein liposarcoma patients with higher E2F4 or E2F1 activity associated with unfavorable prognosis. A total of 259 gene sets were significantly associated with patient survival in liposarcoma, among which >50% are involved in cell cycle and proliferation. PMID:26856934

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2008-10-27

ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Congressional...report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted...40 A related question is whether the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile development programs. A

General Medical Surveillance Program

NASA Technical Reports Server (NTRS)

1993-01-01

Background on the General Medical Surveillance Program at LeRC is presented. The purpose of the General Medical Surveillance Program at LeRC is outlined, and the specifics of the program are discussed.

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program

PubMed Central

Stam, Floor J.; Hendricks, Timothy J.; Zhang, Jingming; Geiman, Eric J.; Francius, Cedric; Labosky, Patricia A.; Clotman, Frederic; Goulding, Martyn

2012-01-01

The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants. PMID:22115757

Increasing Educational Efficiency Through Technology (Commission Discussion and Background Materials).

ERIC Educational Resources Information Center

Indiana State Commission for Higher Education, Indianapolis.

A program schedule and background information for Indiana Commission for Higher Education-sponsored discussion of the use of educational technology to increase educational effeciency are presented. The four major topics of discussion to illustrate the uses and advantages/disadvantages of audio, video, and computing technologies are as follows:…

Adjustment of geochemical background by robust multivariate statistics

USGS Publications Warehouse

Zhou, D.

1985-01-01

Conventional analyses of exploration geochemical data assume that the background is a constant or slowly changing value, equivalent to a plane or a smoothly curved surface. However, it is better to regard the geochemical background as a rugged surface, varying with changes in geology and environment. This rugged surface can be estimated from observed geological, geochemical and environmental properties by using multivariate statistics. A method of background adjustment was developed and applied to groundwater and stream sediment reconnaissance data collected from the Hot Springs Quadrangle, South Dakota, as part of the National Uranium Resource Evaluation (NURE) program. Source-rock lithology appears to be a dominant factor controlling the chemical composition of groundwater or stream sediments. The most efficacious adjustment procedure is to regress uranium concentration on selected geochemical and environmental variables for each lithologic unit, and then to delineate anomalies by a common threshold set as a multiple of the standard deviation of the combined residuals. Robust versions of regression and RQ-mode principal components analysis techniques were used rather than ordinary techniques to guard against distortion caused by outliers Anomalies delineated by this background adjustment procedure correspond with uranium prospects much better than do anomalies delineated by conventional procedures. The procedure should be applicable to geochemical exploration at different scales for other metals. ?? 1985.

Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass

PubMed Central

Portha, Bernard; Chavey, Audrey; Movassat, Jamileh

2011-01-01

A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission. PMID:22110471

The U.N. Population Fund: Background and the U.S. Funding Debate

DTIC Science & Technology

2008-01-11

programs to promote expanded opportunities for the education of women and girls, to end gender discrimination and violence against women, and to...UNFPA annual reports, 1997-2006. CRS-5 5 Obstetric fistula occurs from prolonged child labor, particularly when labor lasts two days or more. When a...Problems in the World: Obstetric Fistula: Background Information and Responses, by Tiaji Salaam-Blyther. UNFPA Program Priorities. Currently, UNFPA

Lack of the programmed death-1 receptor renders host susceptible to enteric microbial infection through impairing the production of the mucosal natural killer cell effector molecules.

PubMed

Solaymani-Mohammadi, Shahram; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Frey, Blake F; Billeskov, Rolf; Singer, Steven M; Berzofsky, Jay A; Eckmann, Lars; Kagnoff, Martin F

2016-03-01

The programmed death-1 receptor is expressed on a wide range of immune effector cells, including T cells, natural killer T cells, dendritic cells, macrophages, and natural killer cells. In malignancies and chronic viral infections, increased expression of programmed death-1 by T cells is generally associated with a poor prognosis. However, its role in early host microbial defense at the intestinal mucosa is not well understood. We report that programmed death-1 expression is increased on conventional natural killer cells but not on CD4(+), CD8(+) or natural killer T cells, or CD11b(+) or CD11c(+) macrophages or dendritic cells after infection with the mouse pathogen Citrobacter rodentium. Mice genetically deficient in programmed death-1 or treated with anti-programmed death-1 antibody were more susceptible to acute enteric and systemic infection with Citrobacter rodentium. Wild-type but not programmed death-1-deficient mice infected with Citrobacter rodentium showed significantly increased expression of the conventional mucosal NK cell effector molecules granzyme B and perforin. In contrast, natural killer cells from programmed death-1-deficient mice had impaired expression of those mediators. Consistent with programmed death-1 being important for intracellular expression of natural killer cell effector molecules, mice depleted of natural killer cells and perforin-deficient mice manifested increased susceptibility to acute enteric infection with Citrobacter rodentium. Our findings suggest that increased programmed death-1 signaling pathway expression by conventional natural killer cells promotes host protection at the intestinal mucosa during acute infection with a bacterial gut pathogen by enhancing the expression and production of important effectors of natural killer cell function. © Society for Leukocyte Biology.

F-35 Joint Strike Fighter (JSF) Program: Background and Issues for Congress

DTIC Science & Technology

2011-04-26

bulkheads on the F-22.”28 Third, the driveshaft, lift-fan clutch, and actuator for the F-35B’s roll-post nozzles will be redesigned following...levels of participation in the program. International partners are also assisting with Initial Operational Test and Evaluation ( IOT &E), a subset of...Week/Ares blog, March 15, 2010. 59 Currently, the UK, Italy, and the Netherlands have agreed to participate in the IOT &E program. UK, the senior F

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-06-04

Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK UNIT...Inside the Navy, October 27, 2008. Another press report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program...X)s could change.38 A related question is whether the schedule for procuring CG(X)s is properly aligned with foreign-country ballistic missile

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-12-22

and Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK...press report (Katherine McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008...changes would have led to a bigger problem—a future surface combatant force that was both unaffordable and poorly aligned with projected mission needs

Why is intracellular ice lethal? A microscopical study showing evidence of programmed cell death in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum

PubMed Central

Wesley-Smith, James; Walters, Christina; Pammenter, N. W.

2015-01-01

Background and Aims Conservation of the genetic diversity afforded by recalcitrant seeds is achieved by cryopreservation, in which excised embryonic axes (or, where possible, embryos) are treated and stored at temperatures lower than −180 °C using liquid nitrogen. It has previously been shown that intracellular ice forms in rapidly cooled embryonic axes of Acer saccharinum (silver maple) but this is not necessarily lethal when ice crystals are small. This study seeks to understand the nature and extent of damage from intracellular ice, and the course of recovery and regrowth in surviving tissues. Methods Embryonic axes of A. saccharinum, not subjected to dehydration or cryoprotection treatments (water content was 1·9 g H2O g−1 dry mass), were cooled to liquid nitrogen temperatures using two methods: plunging into nitrogen slush to achieve a cooling rate of 97 °C s−1 or programmed cooling at 3·3 °C s−1. Samples were thawed rapidly (177 °C s−1) and cell structure was examined microscopically immediately, and at intervals up to 72 h in vitro. Survival was assessed after 4 weeks in vitro. Axes were processed conventionally for optical microscopy and ultrastructural examination. Key Results Immediately following thaw after cryogenic exposure, cells from axes did not show signs of damage at an ultrastructural level. Signs that cells had been damaged were apparent after several hours of in vitro culture and appeared as autophagic decomposition. In surviving tissues, dead cells were sloughed off and pockets of living cells were the origin of regrowth. In roots, regrowth occurred from the ground meristem and procambium, not the distal meristem, which became lethally damaged. Regrowth of shoots occurred from isolated pockets of surviving cells of peripheral and pith meristems. The size of these pockets may determine the possibility for, the extent of and the vigour of regrowth. Conclusions Autophagic degradation and ultimately autolysis of cells following

Theta frequency background tunes transmission but not summation of spiking responses.

PubMed

Parameshwaran, Dhanya; Bhalla, Upinder S

2013-01-01

Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30-135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30-135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations.

Navy CG(X) Cruiser Program: Background, Oversight Issues, and Options for Congress

DTIC Science & Technology

2009-07-17

Options for Congress 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e . TASK NUMBER 5f. WORK...McIntire Peters, “Navy’s Top Officer Sees Lessons in Shipbuilding Program Failures,” GovernmentExecutive.com, September 24, 2008) quoted Admiral Gary...defined, the total required number of CG(X)s could change.38 A related question is whether the schedule for procuring CG(X)s is properly aligned

AtPDCD5 Plays a Role in Programmed Cell Death after UV-B Exposure in Arabidopsis1[OPEN

PubMed Central

Falcone Ferreyra, María Lorena; D’Andrea, Lucio; AbdElgawad, Hamada

2016-01-01

DNA damage responses have evolved to sense and react to DNA damage; the induction of DNA repair mechanisms can lead to genomic restoration or, if the damaged DNA cannot be adequately repaired, to the execution of a cell death program. In this work, we investigated the role of an Arabidopsis (Arabidopsis thaliana) protein, AtPDCD5, which is highly similar to the human PDCD5 protein; it is induced by ultraviolet (UV)-B radiation and participates in programmed cell death in the UV-B DNA damage response. Transgenic plants expressing AtPDCD5 fused to GREEN FLUORESCENT PROTEIN indicate that AtPDCD5 is localized both in the nucleus and the cytosol. By use of pdcd5 mutants, we here demonstrate that these plants have an altered antioxidant metabolism and accumulate higher levels of DNA damage after UV-B exposure, similar to levels in ham1ham2 RNA interference transgenic lines with decreased expression of acetyltransferases from the MYST family. By coimmunoprecipitation and pull-down assays, we provide evidence that AtPDCD5 interacts with HAM proteins, suggesting that both proteins participate in the same pathway of DNA damage responses. Plants overexpressing AtPDCD5 show less DNA damage but more cell death in root tips upon UV-B exposure. Finally, we here show that AtPDCD5 also participates in age-induced programmed cell death. Together, the data presented here demonstrate that AtPDCD5 plays an important role during DNA damage responses induced by UV-B radiation in Arabidopsis and also participates in programmed cell death programs. PMID:26884483

Measles virus: Background and oncolytic virotherapy.

PubMed

Bhattacharjee, Sankhajit; Yadava, Pramod Kumar

2018-03-01

Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins. It was previously proved in our laboratory that N expressing human cancerous cells undergo programmed cell death because of reactive oxygen species (ROS) generation as well as Caspase 3 activation. The phosphoprotein (P) along with N protein enclosed viral genomic RNA forming a ribonucleoprotein complex (RNP). It also establishes interaction with the large protein (L) i.e. viral RNA dependent RNA polymerase to ensure viral replication within host cells. The host cell receptors of this virus are CD46, SLAM/CD150 and PVRL4. Measles virus is latently oncotropic in nature and possesses oncolytic property by syncytia formation. We try to highlight the application of this property in developing a virotherapeutic vehicle.

Commentary: criminal background checks for entering medical students: history, current issues, and future considerations.

PubMed

Kleshinski, James; Case, Steven T; Davis, Dwight; Heinrich, George F; Witzburg, Robert A

2011-07-01

In this commentary, the authors aim to contextualize the history and rationale for what has become the Association of American Medical Colleges-facilitated criminal background check process for entering medical students. As the process was being considered, many issues with a standardized process were identified. There were concerns that demographic or socioeconomic factors might unfairly burden certain applicants or discourage them from applying to medical school. On the other hand, a unified, national program would minimize cost and enhance quality assurance. The authors discuss these issues. Lessons learned in the first three years of the program are also addressed, including some unexpected and favorable consequences such as the identification of accepted applicants with at-risk behaviors (e.g., substance abuse), who would have otherwise gone undetected. Several challenges remain, including the fact that the criminal background check process creates an enhanced role for prehealth advisors and encourages undergraduate institutions to establish standards and processes relating to professionalism. While this is, no doubt, an evolving program which needs continued oversight and ongoing reevaluation, the authors support the continued advancement of the criminal background check process for entering medical students.

Tumor cell membrane-targeting pH-dependent electron donor-acceptor fluorescence systems with low background signals.

PubMed

Han, Liang; Liu, Mingming; Ye, Deyong; Zhang, Ning; Lim, Ed; Lu, Jing; Jiang, Chen

2014-03-01

Minimizing the background signal is crucial for developing tumor-imaging techniques with sufficient specificity and sensitivity. Here we use pH difference between healthy tissues and tumor and tumor targeting delivery to achieve this goal. We synthesize fluorophore-dopamine conjugate as pH-dependent electron donor-acceptor fluorescence system. Fluorophores are highly sensitive to electron-transfer processes, which can alter their optical properties. The intrinsic redox properties of dopamine are oxidation of hydroquinone to quinone at basic pH and reduction of quinone to hydroquinone at acidic pH. Quinone can accept electron then quench fluorescence. We design tumor cell membrane-targeting carrier for delivery. We demonstrate quenched fluorophore-quinone can be specially transferred to tumor extracellular environment and tumor-accumulated fluorophore can be activated by acidic pH. These tumor-targeting pH-dependent electron donor-acceptor fluorescence systems may offer new opportunity for developing tumor-imaging techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Life Functions and Cells: Level II, Unit 7, Lesson 1; Cell Structure: Lesson 2; Tissues, Organs, Systems: Lesson 3; Growth and Nutrition: Lesson 4; Metabolism: Lesson 5. Advanced General Education Program. A High School Self-Study Program.

ERIC Educational Resources Information Center

Manpower Administration (DOL), Washington, DC. Job Corps.

This self-study program for high-school level contains lessons on: Life Functions and Cells; Cell Structure; Tissues, Organs, Systems; Growth and Nutrition; and Metabolism. Each of the lessons concludes with a Mastery Test to be completed by the student. (DB)

Fuel cells

NASA Astrophysics Data System (ADS)

Hooie, D. T.; Harrington, B. C., III; Mayfield, M. J.; Parsons, E. L.

1992-07-01

The primary objective of DOE's Fossil Energy Fuel Cell program is to fund the development of key fuel cell technologies in a manner that maximizes private sector participation and in a way that will give contractors the opportunity for a competitive posture, early market entry, and long-term market growth. This summary includes an overview of the Fuel Cell program, an elementary explanation of how fuel cells operate, and a synopsis of the three major fuel cell technologies sponsored by the DOE/Fossil Energy Phosphoric Acid Fuel Cell program, the Molten Carbonate Fuel Cell program, and the Solid Oxide Fuel Cell program.

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus.

PubMed

Nasi, Aikaterini; Amu, Sylvie; Göthlin, Mårten; Jansson, Marianne; Nagy, Noemi; Chiodi, Francesca; Réthi, Bence

2017-01-01

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus

PubMed Central

Nasi, Aikaterini; Amu, Sylvie; Göthlin, Mårten; Jansson, Marianne; Nagy, Noemi; Chiodi, Francesca; Réthi, Bence

2017-01-01

Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC

Background characterization of an ultra-low background liquid scintillation counter

DOE PAGES

Erchinger, J. L.; Orrell, John L.; Aalseth, C. E.; ...

2017-01-26

The Ultra-Low Background Liquid Scintillation Counter developed by Pacific Northwest National Laboratory will expand the application of liquid scintillation counting by enabling lower detection limits and smaller sample volumes. By reducing the overall count rate of the background environment approximately 2 orders of magnitude below that of commercially available systems, backgrounds on the order of tens of counts per day over an energy range of ~3–3600 keV can be realized. Finally, initial test results of the ULB LSC show promising results for ultra-low background detection with liquid scintillation counting.

Remodelling of lace plant leaves: antioxidants and ROS are key regulators of programmed cell death.

PubMed

Dauphinee, Adrian N; Fletcher, Jacob I; Denbigh, Georgia L; Lacroix, Christian R; Gunawardena, Arunika H L A N

2017-07-01

Antioxidants and reactive oxygen species are integral for programmed cell death signaling during perforation formation in the lace plant ( Aponogeton madagascariensis ). The lace plant is an excellent model system for studying developmentally regulated programmed cell death (PCD). During early lace plant leaf development, PCD systematically deletes cells resulting in a perforated leaf morphology that is unique in planta. A distinct feature in young lace plant leaves is an abundance of anthocyanins, which have antioxidant properties. The first sign of PCD induction is the loss of anthocyanin pigmentation in cells that are targeted for destruction, which results in a visible gradient of cell death. The cellular dynamics and time course of lace plant PCD are well documented; however, the signals involved in the pathway remain elusive. This study investigates the roles of antioxidants and ROS in developmental PCD signaling during lace plant perforation formation. The involvement of antioxidants and ROS in the pathway was determined using a variety of techniques including pharmacological whole plant experimentation, long-term live cell imaging, the 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid anti-radical activity assay, and western blot analysis. Results indicate that antioxidants and ROS are key regulators of PCD during the remodelling of lace plant leaves.

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

PubMed

Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

2014-03-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

Invariant natural killer T-cell control of type 1 diabetes: a dendritic cell genetic decision of a silver bullet or Russian roulette.

PubMed

Driver, John P; Scheuplein, Felix; Chen, Yi-Guang; Grier, Alexandra E; Wilson, S Brian; Serreze, David V

2010-02-01

In part, activation of invariant natural killer T (iNKT)-cells with the superagonist alpha-galactosylceramide (alpha-GalCer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotolerogenic state. However, in other systems iNKT-cell activation has an adjuvant-like effect that enhances rather than suppresses various immunological responses. Thus, we tested whether in some circumstances genetic variation would enable activated iNKT-cells to support rather than inhibit type 1 diabetes development. We tested whether iNKT-conditioned DCs in NOD mice and a major histocompatibility complex-matched C57BL/6 (B6) background congenic stock differed in capacity to inhibit type 1 diabetes induced by the adoptive transfer of pathogenic AI4 CD8 T-cells. Unlike those of NOD origin, iNKT-conditioned DCs in the B6 background stock matured to a state that actually supported rather than inhibited AI4 T-cell-induced type 1 diabetes. The induction of a differing activity pattern of T-cell costimulatory molecules varying in capacity to override programmed death-ligand-1 inhibitory effects contributes to the respective ability of iNKT-conditioned DCs in NOD and B6 background mice to inhibit or support type 1 diabetes development. Genetic differences inherent to both iNKT-cells and DCs contribute to their varying interactions in NOD and B6.H2(g7) mice. This great variability in the interactions between iNKT-cells and DCs in two inbred mouse strains should raise a cautionary note about considering manipulation of this axis as a potential type 1 diabetes prevention therapy in genetically heterogeneous humans.

WE-D-207-01: Background and Clinical Implementation of a Screening Program

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

Aberle, D.

2015-06-15

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical

Influence of antiretroviral therapy on programmed death-1 (CD279) expression on T cells in lymph nodes of human immunodeficiency virus-infected individuals.

PubMed

Ehrhard, Simone; Wernli, Marion; Dürmüller, Ursula; Battegay, Manuel; Gudat, Fred; Erb, Peter

2009-10-01

Human immunodeficiency virus infection leads to T-cell exhaustion and involution of lymphoid tissue. Recently, the programmed death-1 pathway was found to be crucial for virus-specific T-cell exhaustion during human immunodeficiency virus infection. Programmed death-1 expression was elevated on human immunodeficiency virus-specific peripheral blood CD8+ and CD4+ T cells and correlated with disease severity. During human immunodeficiency infection, lymphoid tissue acts as a major viral reservoir and is an important site for viral replication, but it is also essential for regulatory processes important for immune recovery. We compared programmed death-1 expression in 2 consecutive inguinal lymph nodes of 14 patients, excised before antiretroviral therapy (antiretroviral therapy as of 1997-1999) and 16 to 20 months under antiretroviral therapy. In analogy to lymph nodes of human immunodeficiency virus-negative individuals, in all treated patients, the germinal center area decreased, whereas the number of germinal centers did not significantly change. Programmed death-1 expression was mostly found in germinal centers. The absolute extent of programmed death 1 expression per section was not significantly altered after antiretroviral therapy resulting in a significant-relative increase of programmed death 1 per shrunken germinal center. In colocalization studies, CD45R0+ cells that include helper/inducer T cells strongly expressed programmed death-1 before and during therapy, whereas CD8+ T cells, fewer in numbers, showed a weak expression for programmed death-1. Thus, although antiretroviral therapy seems to reduce the number of programmed death-1-positive CD8+ T lymphocytes within germinal centers, it does not down-regulate programmed death-1 expression on the helper/inducer T-cell subset that may remain exhausted and therefore unable to trigger immune recovery.

Evaluation program for secondary spacecraft cells: Initial evaluation tests of Gulton Industries, Incorporated, 9.0 ampere-hour nickel-cadmium spacecraft cells with auxiliary electrodes for the small astronomy Satellite (SAS-C)

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1975-01-01

An evaluation test program was conducted to insure that all cells put into the life cycle program are of high quality by the screening of cells found to have electrolyte leakage, internal shorts, low capacity, or inability of any cell to recover its open-circuit voltage above 1.150 volts during the internal short test. Tests and results are described.

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans

PubMed Central

Sierra, Crystal S.; Haase, Steven B.

2016-01-01

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation. PMID:27918582

Ozone-Induced Cell Death in Tobacco Cultivar Bel W3 Plants. The Role of Programmed Cell Death in Lesion Formation

PubMed Central

Pasqualini, Stefania; Piccioni, Claudia; Reale, Lara; Ederli, Luisa; Della Torre, Guido; Ferranti, Francesco

2003-01-01

Treatment of the ozone-sensitive tobacco (Nicotiana tabacum L. cv Bel W3) with an ozone pulse (150 nL L–1 for 5 h) induced visible injury, which manifested 48 to 72 h from onset of ozone fumigation. The “classical” ozone symptoms in tobacco cv Bel W3 plants occur as sharply defined, dot-like lesions on the adaxial side of the leaf and result from the death of groups of palisade cells. We investigated whether this reaction had the features of a hypersensitive response like that which results from the incompatible plant-pathogen interaction. We detected an oxidative burst, the result of H2O2 accumulation at 12 h from the starting of fumigation. Ozone treatment induced deposition of autofluorescent compounds and callose 24 h from the start of treatment. Total phenolic content was also strongly stimulated at the 10th and 72nd h from starting fumigation, concomitant with an enhancement in phenylalanine ammonia-lyase a and phenylalanine ammonia-lyase b expression, as evaluated by reverse transcriptase-polymerase chain reaction. There was also a marked, but transient, increase in the mRNA level of pathogenesis-related-1a, a typical hypersensitive response marker. Overall, these results are evidence that ozone triggers a hypersensitive response in tobacco cv Bel W3 plants. We adopted four criteria for detecting programmed cell death in ozonated tobacco cv Bel W3 leaves: (a) early release of cytochrome c from mitochondria; (b) activation of protease; (c) DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling of DNA 3′-OH groups; and (d) ultrastructural changes characteristic of programmed cell death, including chromatin condensation and blebbing of plasma membrane. We, therefore, provide evidence that ozone-induced oxidative stress triggers a cell death program in tobacco cv Bel W3. PMID:14612586

Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric oxide on cell proliferation and programmed cell death.

PubMed

Trulsson, Lena M; Gasslander, Thomas; Svanvik, Joar

2004-10-01

The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-kappaB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of N(omega)-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-kappaB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [(3)H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor kappaB (NF-kappaB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-kappaB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-kappaB activation seems not to inhibit apoptosis nor promote cell proliferation.

Electron microprobe analysis program for biological specimens: BIOMAP

NASA Technical Reports Server (NTRS)

Edwards, B. F.

1972-01-01

BIOMAP is a Univac 1108 compatible program which facilitates the electron probe microanalysis of biological specimens. Input data are X-ray intensity data from biological samples, the X-ray intensity and composition data from a standard sample and the electron probe operating parameters. Outputs are estimates of the weight percentages of the analyzed elements, the distribution of these estimates for sets of red blood cells and the probabilities for correlation between elemental concentrations. An optional feature statistically estimates the X-ray intensity and residual background of a principal standard relative to a series of standards.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis.

PubMed

Gadbail, Amol Ramchandra; Chaudhary, Minal; Gawande, Madhuri; Hande, Alka; Sarode, Sachin; Tekade, Satyajit Ashok; Korde, Sheetal; Zade, Prajakta; Bhowate, Rahul; Borle, Rajiv; Patil, Swati

2017-07-01

The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydrogen peroxide production and mitochondrial dysfunction contribute to the fusaric acid-induced programmed cell death in tobacco cells.

PubMed

Jiao, Jiao; Sun, Ling; Zhou, Benguo; Gao, Zhengliang; Hao, Yu; Zhu, Xiaoping; Liang, Yuancun

2014-08-15

Fusaric acid (FA), a non-specific toxin produced mainly by Fusarium spp., can cause programmed cell death (PCD) in tobacco suspension cells. The mechanism underlying the FA-induced PCD was not well understood. In this study, we analyzed the roles of hydrogen peroxide (H2O2) and mitochondrial function in the FA-induced PCD. Tobacco suspension cells were treated with 100 μM FA and then analyzed for H2O2 accumulation and mitochondrial functions. Here we demonstrate that cells undergoing FA-induced PCD exhibited H2O2 production, lipid peroxidation, and a decrease of the catalase and ascorbate peroxidase activities. Pre-treatment of tobacco suspension cells with antioxidant ascorbic acid and NADPH oxidase inhibitor diphenyl iodonium significantly reduced the rate of FA-induced cell death as well as the caspase-3-like protease activity. Moreover, FA treatment of tobacco cells decreased the mitochondrial membrane potential and ATP content. Oligomycin and cyclosporine A, inhibitors of the mitochondrial ATP synthase and the mitochondrial permeability transition pore, respectively, could also reduce the rate of FA-induced cell death significantly. Taken together, the results presented in this paper demonstrate that H2O2 accumulation and mitochondrial dysfunction are the crucial events during the FA-induced PCD in tobacco suspension cells. Copyright © 2014 Elsevier GmbH. All rights reserved.

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent

PubMed Central

van Erp, Anke E.M.; Versleijen-Jonkers, Yvonne M.H.; Hillebrandt-Roeffen, Melissa H.S.; van Houdt, Laurens; Gorris, Mark A.J.; van Dam, Laura S.; Mentzel, Thomas; Weidema, Marije E.; Savci-Heijink, C. Dilara; Desar, Ingrid M.E.; Merks, Hans H.M.; van Noesel, Max M.; Shipley, Janet; van der Graaf, Winette T.A.; Flucke, Uta E.; Meyer-Wentrup, Friederike A.G.

2017-01-01

In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described. PMID:29050367

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent.

PubMed

van Erp, Anke E M; Versleijen-Jonkers, Yvonne M H; Hillebrandt-Roeffen, Melissa H S; van Houdt, Laurens; Gorris, Mark A J; van Dam, Laura S; Mentzel, Thomas; Weidema, Marije E; Savci-Heijink, C Dilara; Desar, Ingrid M E; Merks, Hans H M; van Noesel, Max M; Shipley, Janet; van der Graaf, Winette T A; Flucke, Uta E; Meyer-Wentrup, Friederike A G

2017-09-19

In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma ( n = 46), Ewing sarcoma ( n = 32), alveolar rhabdomyosarcoma ( n = 20), embryonal rhabdomyosarcoma ( n = 77), synovial sarcoma ( n = 22) and desmoplastic small round cell tumors (DSRCT) ( n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described.

Cycle life test. Evaluation program for secondary spacecraft cells. [performance tests on silver zinc batteries, silver cadmium batteries, and nickel cadmium batteries

NASA Technical Reports Server (NTRS)

Harkness, J. D.

1976-01-01

Considerable research is being done to find more efficient and reliable means of starting electrical energy for orbiting satellites. Rechargeable cells offer one such means. A test program is described which has been established in order to further the evaluation of certain types of cells and to obtain performance and failure data as an aid to their continued improvement. The purpose of the program is to determine the cycling performance capabilities of packs of cells under different load and temperature conditions. The various kinds of cells tested were nickel-cadmium, silver-cadmium, and silver-zinc sealed cells. A summary of the results of the life cycling program is given in this report.

The Effect of Background Music on Bullying: A Pilot Study

ERIC Educational Resources Information Center

Ziv, Naomi; Dolev, Einat

2013-01-01

School bullying is a source of growing concern. A number of intervention programs emphasize the importance of a positive school climate in preventing bullying behavior. The aim of the presented pilot study was to examine whether calming background music, through its effect on arousal and mood, could create a pleasant atmosphere and reduce bullying…

Microtubule antagonists activate programmed cell death (apoptosis) in cultured rat hepatocytes.

PubMed Central

Tsukidate, K.; Yamamoto, K.; Snyder, J. W.; Farber, J. L.

1993-01-01

We investigated the mechanism of lethal injury following the disruption of microtubules in cultured hepatocytes treated with vinblastine (VBL) or colchicine (COL). These agents kill hepatocytes by a process readily distinguished from two well-known pathways that lead to a loss of viability, namely, oxidative stress and inhibition of mitochondrial electron transport. Cell killing with VBL and COL was accompanied by fragmentation of DNA. Both the loss of viability and the fragmentation of DNA were prevented by the inhibition of protein synthesis within 6 hours following exposure to VBL or COL. Cell death and the fragmentation of DNA were also prevented when Ca2+ was removed from the culture medium. By contrast, the inhibition of protein kinase C prevented cell killing by VBL or COL, but did not alter the extent of DNA fragmentation. The requirements here for protein synthesis, extracellular Ca2+, and protein kinase C activity define a model of apoptosis, or programmed cell death, that seems to involve mechanisms that can be dissociated from the fragmentation of DNA. Images Figure 2 PMID:8362985

78 FR 15374 - Notice of Formula Allocations and Program Requirements for Neighborhood Stabilization Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... (or NSP) was established by the Housing and Economic Recovery Act of 2008 (HERA) (Pub. L. 110-289... background for the program, the program principles, and the objectives and outcomes of the NSP program. NSP...

A unidirectional acoustic cloak for multilayered background media with homogeneous metamaterials

NASA Astrophysics Data System (ADS)

Zhu, Jian; Chen, Tianning; Liang, Qingxuan; Wang, Xiaopeng; Xiong, Jie; Jiang, Ping

2015-08-01

The acoustic cloak, which can make an object hard to detect acoustically in a homogeneous background, has attracted great attention from researchers in recent years. The inhomogeneous background media were considered in this paper. The relative constitutive parameters were derived for acoustic cloaks working in multilayered media. And a unidirectional acoustic cloak for layered background media was proposed, designed and implemented successfully in a wide frequency range. In water and NaCl aqueous solution, the acoustic cloak was designed and realized with homogeneous metamaterials which were composed of steel and porous materials. The effective parameters of the unit cells of the cloak were determined by using the effective medium theory. Numerical results demonstrated excellent cloaking performance and showed that such a device could be physically realized with natural materials which will greatly promote the real applications of an invisibility cloak in inhomogeneous backgrounds.

DOE Hydrogen and Fuel Cells Program 2017 Annual Merit Review and Peer Evaluation Report

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

None, None

The fiscal year 2017 U.S. Department of Energy (DOE) Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting (AMR), in conjunction with DOE's Vehicle Technologies Office AMR, was held from June June 5-9, 2017, in Washington, D.C. This report is a summary of comments by AMR peer reviewers about the hydrogen and fuel cell projects funded by DOE's Office of Energy Efficiency and Renewable Energy.

DOE Hydrogen and Fuel Cells Program 2016 Annual Merit Review and Peer Evaluation Report

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

None, None

The fiscal year 2016 U.S. Department of Energy (DOE) Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting (AMR), in conjunction with DOE's Vehicle Technologies Office AMR, was held from June 6-10, 2016, in Washington, D.C. This report is a summary of comments by AMR peer reviewers about the hydrogen and fuel cell projects funded by DOE's Office of Energy Efficiency and Renewable Energy.

Bootstrapping a Sustainable North American PEM Fuel Cell Industry: Could a Federal Acquisition Program Make a Difference?

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

Greene, David L; Duleep, Dr. K. G.

2008-10-01

The North American Proton Exchange Membrane (PEM) fuel cell industry may be at a critical juncture. A large-scale market for automotive fuel cells appears to be several years away and in any case will require a long-term, coordinated commitment by government and industry to insure the co-evolution of hydrogen infrastructure and fuel cell vehicles (Greene et al., 2008). The market for non-automotive PEM fuel cells, on the other hand, may be much closer to commercial viability (Stone, 2006). Cost targets are less demanding and manufacturers appear to be close, perhaps within a factor of two, of meeting them. Hydrogen supplymore » is a significant obstacle to market acceptance but may not be as great a barrier as it is for hydrogen-powered vehicles due to the smaller quantities of hydrogen required. PEM fuel cells appear to be potentially competitive in two markets: (1) Backup power (BuP) supply, and (2) electrically-powered MHE (Mahadevan et al., 2007a, 2007b). There are several Original Equipment Manufacturers (OEMs) of PEM fuel cell systems for these applications but production levels have been quite low (on the order of 100-200 per year) and cumulative production experience is also limited (on the order of 1,000 units to date). As a consequence, costs remain above target levels and PEM fuel cell OEMs are not yet competitive in these markets. If cost targets can be reached and acceptable solutions to hydrogen supply found, a sustainable North American PEM fuel cell industry could be established. If not, the industry and its North American supply chain could disappear within a year or two. The Hydrogen Fuel Cell and Infrastructure Technologies (HFCIT) program of the U.S. Department of Energy (DOE) requested a rapid assessment of the potential for a government acquisition program to bootstrap the market for non-automotive PEM fuel cells by driving down costs via economies of scale and learning-by-doing. The six week study included in-depth interviews of three

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.

PubMed

Cummings, Ryan J; Barbet, Gaetan; Bongers, Gerold; Hartmann, Boris M; Gettler, Kyle; Muniz, Luciana; Furtado, Glaucia C; Cho, Judy; Lira, Sergio A; Blander, J Magarian

2016-11-24

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4 + T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4 + T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs

PubMed Central

Cummings, Ryan J.; Barbet, Gaetan; Bongers, Gerold; Hartmann, Boris M.; Gettler, Kyle; Muniz, Luciana; Furtado, Glaucia C.; Cho, Judy; Lira, Sergio A.; Blander, J. Magarian

2017-01-01

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies1,2. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions3, are not merely extruded to maintain homeostatic cell numbers4, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria5,6. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common ‘suppression of inflammation’ signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease7. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the

Argonne National Laboratory Li-alloy/FeS cell testing and R and D programs

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

Gay, E.C.

1982-01-01

Groups of 12 or more identical Li-alloy/FeS cells fabricated by Eagle-Picher Industries, Inc. and Gould Inc. were operated at Argonne National Laboratory (ANL) in the status cell test program to obtain data for statistical analysis of cell cycle life and failure modes. The cells were full-size electric vehicle battery cells (150 to 350 Ah capacity) and they were cycled at the 4-h discharge rate and 8-h charge rate. The end of life was defined as a 20% loss of capacity or a decrease in the coulombic efficiency to less than 95%. Seventy-four cells (six groups of identical cells) were cycle-lifemore » tested and the results were analyzed statistically. The ultimate goal of this analysis was to predict cell and battery reliability. Testing of groups of identical cells also provided a means of identifying common failure modes which were eliminated by cell design changes. Mean time to failure (MTTF) for the cells based on the Weibull distribution is presented.« less

Generation of sensory hair cells by genetic programming with a combination of transcription factors.

PubMed

Costa, Aida; Sanchez-Guardado, Luis; Juniat, Stephanie; Gale, Jonathan E; Daudet, Nicolas; Henrique, Domingos

2015-06-01

Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration. © 2015. Published by The Company of Biologists Ltd.

Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells.

PubMed

Liu, Mengling; Xia, Yingfeng; Ding, Jane; Ye, Bingwei; Zhao, Erhu; Choi, Jeong-Hyeon; Alptekin, Ahmet; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Yang, Liqun; Cui, Hongjuan; Zha, Yunhong; Ding, Han-Fei

2016-10-04

High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Programming Cells for Dynamic Assembly of Inorganic Nano-Objects with Spatiotemporal Control.

PubMed

Wang, Xinyu; Pu, Jiahua; An, Bolin; Li, Yingfeng; Shang, Yuequn; Ning, Zhijun; Liu, Yi; Ba, Fang; Zhang, Jiaming; Zhong, Chao

2018-04-01

Programming living cells to organize inorganic nano-objects (NOs) in a spatiotemporally precise fashion would advance new techniques for creating ordered ensembles of NOs and new bio-abiotic hybrid materials with emerging functionalities. Bacterial cells often grow in cellular communities called biofilms. Here, a strategy is reported for programming dynamic biofilm formation for the synchronized assembly of discrete NOs or hetero-nanostructures on diverse interfaces in a dynamic, scalable, and hierarchical fashion. By engineering Escherichia coli to sense blue light and respond by producing biofilm curli fibers, biofilm formation is spatially controlled and the patterned NOs' assembly is simultaneously achieved. Diverse and complex fluorescent quantum dot patterns with a minimum patterning resolution of 100 µm are demonstrated. By temporally controlling the sequential addition of NOs into the culture, multilayered heterostructured thin films are fabricated through autonomous layer-by-layer assembly. It is demonstrated that biologically dynamic self-assembly can be used to advance a new repertoire of nanotechnologies and materials with increasing complexity that would be otherwise challenging to produce. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis.

PubMed

Kato, Mihoko; Sternberg, Paul W

2009-12-01

Cell migration is a common event during organogenesis, yet little is known about how migration is temporally coordinated with organ development. We are investigating stage-specific programs of cell migration using the linker cell (LC), a migratory cell crucial for male gonadogenesis of C. elegans. During the L3 and L4 larval stages of wild-type males, the LC undergoes changes in its position along the migratory route, in transcriptional regulation of the unc-5 netrin receptor and zmp-1 zinc matrix metalloprotease, and in cell morphology. We have identified the tailless homolog nhr-67 as a cell-autonomous, stage-specific regulator of timing in LC migration programs. In nhr-67-deficient animals, each of the L3 and L4 stage changes is either severely delayed or never occurs, yet LC development before the early L3 stage or after the mid-L4 stage occurs with normal timing. We propose that there is a basal migration program utilized throughout LC migration that is modified by stage-specific regulators such as nhr-67.

Quasi-programmed aging of budding yeast: a trade-off between programmed processes of cell proliferation, differentiation, stress response, survival and death defines yeast lifespan

PubMed Central

Arlia-Ciommo, Anthony; Piano, Amanda; Leonov, Anna; Svistkova, Veronika; Titorenko, Vladimir I

2014-01-01

Recent findings suggest that evolutionarily distant organisms share the key features of the aging process and exhibit similar mechanisms of its modulation by certain genetic, dietary and pharmacological interventions. The scope of this review is to analyze mechanisms that in the yeast Saccharomyces cerevisiae underlie: (1) the replicative and chronological modes of aging; (2) the convergence of these 2 modes of aging into a single aging process; (3) a programmed differentiation of aging cell communities in liquid media and on solid surfaces; and (4) longevity-defining responses of cells to some chemical compounds released to an ecosystem by other organisms populating it. Based on such analysis, we conclude that all these mechanisms are programs for upholding the long-term survival of the entire yeast population inhabiting an ecological niche; however, none of these mechanisms is a ʺprogram of agingʺ - i.e., a program for progressing through consecutive steps of the aging process. PMID:25485579

Background and Recent Progress in Anomalous Transport Simulation

DTIC Science & Technology

2017-07-19

NUMBER (Include area code) 19 July 2017 Briefing Charts 14 June 2017 - 19 July 2017 Background and Recent Progress in Anomalous Transport Simulation ...and Recent Progress in Anomalous Transport Simulation 19 Jul 2017 Justin Koo AFRL/RQRS Edwards AFB, CA 2DISTRIBUTION A: Approved for public release...Baalrud, S.D. and Chabert, P., “Theory for the anomalous electron transport in Hall effect thrusters. I. Insights from particle-in-cell simulations

Melatonin, a natural programmed cell death inducer in cancer.

PubMed

Sánchez-Hidalgo, M; Guerrero, J M; Villegas, I; Packham, G; de la Lastra, C A

2012-01-01

Melatonin, an indolamine derived from the amino-acid tryptophan, participates in diverse physiological functions and has great functional versatility related to the regulation of circadian rhythms and seasonal behaviour, sexual development, retinal physiology, tumour inhibition, as an antioxidant, immunomodulatory and anti-aging properties. In relation to its oncostatic properties, there is evidence that tumor initiation, promotion or progression may be restrained by the night-time physiological surge of melatonin in the blood or extracellular fluid. In addition, depressed nocturnal melatonin concentrations or nocturnal excretion of the main melatonin metabolite, 6-sulfatoxymelatonin, were found in individuals with various tumor types. In the majority of studies, melatonin was shown to inhibit development and/or growth of various experimental animal tumors and some human cell lines in vitro. Many tumors do not respond to drug treatment due to their resistance to undergo apoptosis thereby contributing to the development of cancer. Thus, given the importance of the apoptotic program in cancer treatment, the role of melatonin in influencing apoptosis in tumor cells attracted attention because it seems that it actually promotes apoptosis in most tumor cells, in contrast to the obvious inhibition of apoptotic processes in normal cells. Thus, this paper is also intended to provide to the reader an up-date of all the researches that have been carried out to date, which investigate the proapoptotic effects of melatonin in experimental preclinical models of cancer (in vitro and in vivo) and the underlying proposed action mechanism of this effects. If melatonin uniformly induces apoptosis in cancer cells, the findings could have important clinical implications to improve the quality of live while preventing the appearance of cancer.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

PubMed Central

Moreau, Thomas; Evans, Amanda L.; Vasquez, Louella; Tijssen, Marloes R.; Yan, Ying; Trotter, Matthew W.; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M.; Pask, Dean C.; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H.; Pedersen, Roger A.; Ghevaert, Cedric

2016-01-01

The production of megakaryocytes (MKs)—the precursors of blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology. PMID:27052461

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

PubMed

Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

2016-04-07

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

Radioprotective Effects of Sulfur-containing Mineral Water of Ramsar Hot Spring with High Natural Background Radiation on Mouse Bone Marrow Cells.

PubMed

Heidari, A H; Shabestani Monfared, A; Mozdarani, H; Mahmoudzadeh, A; Razzaghdoust, A

2017-12-01

We intend to study the inhibitory effect of sulfur compound in Ramsar hot spring mineral on tumor-genesis ability of high natural background radiation. The radioprotective effect of sulfur compounds was previously shown on radiation-induced chromosomal aberration, micronuclei in mouse bone marrow cells and human peripheral lymphocyte. Ramsar is known for having the highest level of natural background radiation on Earth. This study was performed to show the radioprotective effect of sulfur-containing Ramsar mineral water on mouse bone marrow cells. Mice were fed three types of water (drinking water, Ramsar radioactive water containing sulfur and Ramsar radioactive water whose sulfur was removed). Ten days after feeding, mice were irradiated by gamma rays (0, 2 and 4 Gy). 48 and 72 hours after irradiating, mice were killed and femurs were removed. Frequency of micronuclei was determined in bone marrow erythrocytes. A significant reduction was shown in the rate of micronuclei polychromatic erythrocyte in sulfur-containing hot spring water compared to sulfur-free water in hot spring mineral water. Gamma irradiation induced significant increases in micronuclei polychromatic erythrocyte (MNPCE) and decreases in polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte ratio (PCEs/PCEs+NCEs) (P < 0.001) in sulfur-containing hot spring water compared to sulfur-free hot spring mineral water. Also, apparently there was a significant difference between drinking water and sulfur-containing hot spring water in micronuclei polychromatic erythrocyte and polychromatic erythrocyte/polychromatic erythrocyte+ normochromatic erythrocyte ratio. The results indicate that sulfur-containing mineral water could result in a significant reduction in radiation-induced micronuclei representing the radioprotective effect of sulfur compounds.

Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.

PubMed

Hayano, Azusa; Komohara, Yoshihiro; Takashima, Yasuo; Takeya, Hiroto; Homma, Jumpei; Fukai, Junya; Iwadate, Yasuo; Kajiwara, Koji; Ishizawa, Shin; Hondoh, Hiroaki; Yamanaka, Ryuya

2017-10-01

Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs). PD-L1 protein and mRNA expression were evaluated in 64 PCNSL tissue samples. IFN-γ, IL-10, CD4, and CD8 mRNA expression was also evaluated. PD-L1 protein was detected in tumor cells in 2 (4.1%) cases and in tumor microenvironments in 25 (52%) cases. PD-L1 mRNA positively correlated with IFN-γ (p=0.0024) and CD4 (p=0.0005) mRNA expression. IFN-γ mRNA positively correlated with CD8 mRNA expression (p=0.0001). Furthermore, tumor cell PD-L1 expression correlated positively with overall survival (p=0.0177), whereas microenvironmental PD-L1 expression exhibited an insignificant negative trend with overall survival (p=0.188). PD-L1 was expressed on both tumor and/or tumor-infiltrating immune cells in PCNSL. The biological roles of this marker warrant further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations.

PubMed

Keenan, Alexandra B; Jenkins, Sherry L; Jagodnik, Kathleen M; Koplev, Simon; He, Edward; Torre, Denis; Wang, Zichen; Dohlman, Anders B; Silverstein, Moshe C; Lachmann, Alexander; Kuleshov, Maxim V; Ma'ayan, Avi; Stathias, Vasileios; Terryn, Raymond; Cooper, Daniel; Forlin, Michele; Koleti, Amar; Vidovic, Dusica; Chung, Caty; Schürer, Stephan C; Vasiliauskas, Jouzas; Pilarczyk, Marcin; Shamsaei, Behrouz; Fazel, Mehdi; Ren, Yan; Niu, Wen; Clark, Nicholas A; White, Shana; Mahi, Naim; Zhang, Lixia; Kouril, Michal; Reichard, John F; Sivaganesan, Siva; Medvedovic, Mario; Meller, Jaroslaw; Koch, Rick J; Birtwistle, Marc R; Iyengar, Ravi; Sobie, Eric A; Azeloglu, Evren U; Kaye, Julia; Osterloh, Jeannette; Haston, Kelly; Kalra, Jaslin; Finkbiener, Steve; Li, Jonathan; Milani, Pamela; Adam, Miriam; Escalante-Chong, Renan; Sachs, Karen; Lenail, Alex; Ramamoorthy, Divya; Fraenkel, Ernest; Daigle, Gavin; Hussain, Uzma; Coye, Alyssa; Rothstein, Jeffrey; Sareen, Dhruv; Ornelas, Loren; Banuelos, Maria; Mandefro, Berhan; Ho, Ritchie; Svendsen, Clive N; Lim, Ryan G; Stocksdale, Jennifer; Casale, Malcolm S; Thompson, Terri G; Wu, Jie; Thompson, Leslie M; Dardov, Victoria; Venkatraman, Vidya; Matlock, Andrea; Van Eyk, Jennifer E; Jaffe, Jacob D; Papanastasiou, Malvina; Subramanian, Aravind; Golub, Todd R; Erickson, Sean D; Fallahi-Sichani, Mohammad; Hafner, Marc; Gray, Nathanael S; Lin, Jia-Ren; Mills, Caitlin E; Muhlich, Jeremy L; Niepel, Mario; Shamu, Caroline E; Williams, Elizabeth H; Wrobel, David; Sorger, Peter K; Heiser, Laura M; Gray, Joe W; Korkola, James E; Mills, Gordon B; LaBarge, Mark; Feiler, Heidi S; Dane, Mark A; Bucher, Elmar; Nederlof, Michel; Sudar, Damir; Gross, Sean; Kilburn, David F; Smith, Rebecca; Devlin, Kaylyn; Margolis, Ron; Derr, Leslie; Lee, Albert; Pillai, Ajay

2018-01-24

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability. Copyright © 2017 Elsevier Inc. All rights reserved.

Logic programming to predict cell fate patterns and retrodict genotypes in organogenesis.

PubMed

Hall, Benjamin A; Jackson, Ethan; Hajnal, Alex; Fisher, Jasmin

2014-09-06

Caenorhabditis elegans vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based models, coupled with formal analysis techniques, has been established as a powerful approach in predicting the outcome of combinations of mutations. However, computing the outcomes of complex and highly concurrent models can become prohibitive. Here, we show how logic programs derived from state machines describing the differentiation of C. elegans vulval precursor cells can increase the speed of prediction by four orders of magnitude relative to previous approaches. Moreover, this increase in speed allows us to infer, or 'retrodict', compatible genomes from cell fate patterns. We exploit this technique to predict highly variable cell fate patterns resulting from dig-1 reduced-function mutations and let-23 mosaics. In addition to the new insights offered, we propose our technique as a platform for aiding the design and analysis of experimental data. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

A successful education program for parents of infants with newly diagnosed sickle cell disease.

PubMed

Day, S; Brunson, G; Wang, W

1992-02-01

The most dramatic recent advance in the care of young children with sickle cell disease was the demonstration by a cooperative study that the use of oral penicillin prophylaxis is highly effective in decreasing the risk of pneumococcal sepsis. Subsequently, the need for more comprehensive education of the parents of these children to ensure compliance with penicillin administration has become apparent. Over the past 4 years, the Mid-South Sickle Cell Disease Program has used a seven-phase educational process for the parents of more than 200 infants with newly diagnosed sickle cell disease. This has resulted in excellent compliance and a marked decrease in the incidence of pneumococcal sepsis among sickle cell patients at our center.

Programmed cell death of tobacco BY-2 cells induced by still culture conditions is affected by the age of the culture under agitation.

PubMed

Hiraga, Asahi; Kaneta, Tsuyoshi; Sato, Yasushi; Sato, Seiichi

2010-01-25

Evans Blue staining indicated that actively growing tobacco BY-2 cells in the exponential phase died more rapidly than quiescent cells in the stationary phase when the cells cultured under agitation were placed under still conditions. Fifty percent cell death was induced at about 18, 26, 80 and 140 h for early, mid, late exponential- and stationary-phase cells, respectively. Actively growing cells became TUNEL (transferase-mediated dUTP nick end labelling)-positive more rapidly than quiescent cells, suggesting that the cell death evaluated by Evans Blue is accompanied by DNA cleavages. Electrophoresis of genomic DNA showed a typical 'DNA laddering' pattern formed by multiples of about 200 bp internucleosomal units. Chromatin condensation was first detected at least within 24 h by light microscopy, and then cell shrinkage followed. These findings suggest that the death of BY-2 cells induced by still conditions is PCD (programmed cell death).

Characterization of the programmed cell death induced by metabolic products of Alternaria alternata in tobacco BY-2 cells.

PubMed

Cheng, Dan-Dan; Jia, Yu-Jiao; Gao, Hui-Yuan; Zhang, Li-Tao; Zhang, Zi-Shan; Xue, Zhong-Cai; Meng, Qing-Wei

2011-02-01

Alternaria alternata has received considerable attention in current literature and most of the studies are focused on its pathogenic effects on plant chloroplasts, but little is known about the characteristics of programmed cell death (PCD) induced by metabolic products (MP) of A. alternata, the effects of the MP on mitochondrial respiration and its relation to PCD. The purpose of this study was to explore the mechanism of MP-induced PCD in non-green tobacco BY-2 cells and to explore the role of mitochondrial inhibitory processes in the PCD of tobacco BY-2 cells. MP treatment led to significant cell death that was proven to be PCD by the concurrent cytoplasm shrinkage, chromatin condensation and DNA laddering observed in the cells. Moreover, MP treatment resulted in the overproduction of reactive oxygen species (ROS), rapid ATP depletion and a respiratory decline in the tobacco BY-2 cells. It was concluded that the direct inhibition of the mitochondrial electron transport chain (ETC), alternative pathway (AOX) capacity and catalase (CAT) activity by the MP might be the main contributors to the MP-induced ROS burst observed in tobacco BY-2 cells. The addition of adenosine together with the MP significantly inhibited ATP depletion without preventing PCD; however, when the cells were treated with the MP plus CAT, ROS overproduction was blocked and PCD did not occur. The data presented here demonstrate that the ROS burst played an important role in MP-induced PCD in the tobacco BY-2 cells.

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells

PubMed Central

Monetti, Emanuela; Kadono, Takashi; Bouteau, François

2014-01-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571