Sample records for raising cre strategic

  1. Strategic Forum. Number 274. January 2012. Raising Our Sights: Russian-American Strategic Restraint in an Age of Vulnerability

    DTIC Science & Technology

    2012-01-01

    leader. Although Russians remain wary of the United States, perpetuating and accenting American- Russian dif- ferences is no longer the formula for...truly seek a nonadversarial relationship, each can agree not to be the Raising Our Sights: Russian - American Strategic Restraint in an Age of...Raising Our Sights: Russian -American Strategic Restraint in an Age of Vulnerability 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  2. Conditional transgenesis using Dimerizable Cre (DiCre).

    PubMed

    Jullien, Nicolas; Goddard, Isabelle; Selmi-Ruby, Samia; Fina, Jean-Luc; Cremer, Harold; Herman, Jean-Paul

    2007-12-26

    Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin associated protein), respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activity, and presents a low background activity together with a high efficiency of recombination following dimerization. To test the in vivo performance of this system, we have, in the present work, knocked-in DiCre into the Rosa26 locus of mice. To evaluate the performance of the DiCre system, mice have been mated with indicator mice (Z/EG or R26R) and Cre-induced recombination was examined following activation of DiCre by rapamycin during embryonic development or after birth of progenies. No recombination could be observed in the absence of treatment of the animals, indicating a lack of background activity of DiCre in the absence of rapamycin. Postnatal rapamycin treatment (one to five daily injection, 10 mg/kg i.p) induced recombination in a number of different tissues of progenies such as liver, heart, kidney, muscle, etc. On the other hand, recombination was at a very low level following in utero treatment of DiCrexR26R mice. In conclusion, DiCre has indeed the potentiality to be used to establish conditional Cre-deleter mice. An added advantage of this system is that, contrary to other modulatable Cre systems, it offers the possibility of obtaining regulated recombination in a combinatorial manner, i.e. induce recombination at

  3. Essential Not Optional: A Strategic Approach to Fund-Raising for Endowments

    ERIC Educational Resources Information Center

    Griswold, John S.; Jarvis, William F.

    2012-01-01

    This overview of the state of endowment giving comes at a time of urgent need in the nonprofit sector. With market returns uncertain, and spending restraint difficult, the moderate but measurable increase in donations in the previous year invites institutions to consider elevating fund-raising to a more strategic position within the organization.…

  4. The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans.

    PubMed

    Alam, Md Ashiqul; Kamlangdee, Niyom; Kelly, Joan M

    2017-08-01

    Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism. Previously, missense alleles of creA and creB were analysed for genetic interactions, and here we extended this to complete loss-of-function alleles of creA and creB, and compared morphological and biochemical phenotypes, which confirmed genetic interaction between the genes. We investigated whether CreA, or a protein in a complex with it, is a direct target of the CreB deubiquitination enzyme, using co-purifications of CreA and CreB, first using strains that overexpress the proteins and then using strains that express the proteins from their native promoters. The Phos-tag system was used to show that CreA is a phosphorylated protein, but no ubiquitination was detected using anti-ubiquitin antibodies and Western analysis. These findings were confirmed using mass spectrometry, which confirmed that CreA was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a direct target of CreB, and nor are proteins that form part of a stable complex with CreA a target of CreB. These results open up new questions regarding the molecular mechanism of CreA repressing activity, and how the ubiquitination pathway involving CreB interacts with this regulatory network.

  5. Characteristics of sensory neuronal groups in CGRP-cre-ER reporter mice: Comparison to Nav1.8-cre, TRPV1-cre and TRPV1-GFP mouse lines.

    PubMed

    Patil, Mayur J; Hovhannisyan, Anahit H; Akopian, Armen N

    2018-01-01

    Peptidergic sensory neurons play a critical role in nociceptive pathways. To precisely define the function and plasticity of sensory neurons in detail, new tools such as transgenic mouse models are needed. We employed electrophysiology and immunohistochemistry to characterize in detail dorsal root ganglion (DRG) neurons expressing an inducible CGRPcre-ER (CGRP-cre+); and compared them to DRG neurons expressing Nav1.8cre (Nav1.8-cre+), TRPV1cre (TRPV1-cre+) and TRPV1-GFP (V1-GFP+). Tamoxifen effectively induced CGRPcre-ER production in DRG. ≈87% of CGRPcre-ER-expressing neurons were co-labeled CGRP antibody. Three small and two medium-large-sized (5HT3a+/NPY2R- and NPY2R+) neuronal groups with unique electrophysiological profiles were CGRP-cre+. Nav1.8-cre+ neurons were detected in all CGRP-cre+ groups, as well as in 5 additional neuronal groups: MrgprD+/TRPA1-, MrgprD+/TRPA1+, TRPV1+/CGRP-, vGLUT3+ and ≈30% of trkC+ neurons. Differences between TRPV1cre and Nav1.8cre reporters were that unlike TRPV1-cre+, Nav1.8-cre+ expression was detected in non-nociceptive vGLUT3+ and trkC+ populations. Many TRPV1-cre+ neurons did not respond to capsaicin. In contrast, V1-GFP+ neurons were in 4 groups, each of which was capsaicin-sensitive. Finally, none of the analyzed reporter lines showed cre-recombination in trkB+, calbindin+, 70% of trkC+ or parvalbumin+ neurons, which together encompassed ≈20% of Nav1.8-cre- DRG neurons. The data presented here increases our knowledge of peptidergic sensory neuron characteristics, while showing the efficiency and specificity manipulation of peptidergic neurons by the CGRPcre-ER reporter. We also demonstrate that manipulation of all C- and A-nociceptors is better achieved with TRPV1-cre reporter. Finally, the described approach for detailed characterization of sensory neuronal groups can be applied to a variety of reporter mice.

  6. Flp and Cre expressed from Flp–2A–Cre and Flp–IRES–Cre transcription units mediate the highest level of dual recombinase-mediated cassette exchange

    PubMed Central

    Anderson, Rachelle P.; Voziyanova, Eugenia; Voziyanov, Yuri

    2012-01-01

    Recombinase-mediated cassette exchange (RMCE) is a powerful tool for unidirectional integration of DNA fragments of interest into a pre-determined genome locale. In this report, we examined how the efficiency of dual RMCE catalyzed by Flp and Cre depends on the nature of transcription units that express the recombinases. The following recombinase transcription units were analyzed: (i) Flp and Cre genes expressed as individual transcription units located on different vectors, (ii) Flp and Cre genes expressed as individual transcription units located on the same vector, (iii) Flp and Cre genes expressed from a single promoter and separated by internal ribosome entry sequence and (iv) Flp and Cre coding sequences separated by the 2A peptide and expressed as a single gene. We found that the highest level of dual RMCE (35–45% of the transfected cells) can be achieved when Flp and Cre recombinases are expressed as Flp–2A–Cre and Flp–IRES–Cre transcription units. In contrast, the lowest level of dual RMCE (∼1% of the transfected cells) is achieved when Flp and Cre are expressed as individual transcription units. The analysis shows that it is the relative Flp–to–Cre ratio that critically affects the efficiency of dual RMCE. Our results will be helpful for maximizing the efficiency of dual RMCE aimed to engineer and re-engineer genomes. PMID:22270085

  7. Raising financing through strategic timing

    NASA Astrophysics Data System (ADS)

    Maine, Elicia; Thomas, V. J.

    2017-02-01

    Strategic timing can be key for nano-drug-delivery ventures to get financing. Timely publications engage potential partners; early broad, blocking, relevant patents demonstrate the potential to appropriate value; and venture formation closer to clinical viability better aligns its timeline with that of venture capitalists.

  8. Germ-Line Recombination Activity of the Widely Used hGFAP-Cre and Nestin-Cre Transgenes

    PubMed Central

    Zhang, Jiong; Dublin, Pavel; Griemsmann, Stephanie; Klein, Alexandra; Brehm, Ralph; Bedner, Peter; Fleischmann, Bernd K.; Steinhäuser, Christian; Theis, Martin

    2013-01-01

    Herein we demonstrate with PCR, immunodetection and reporter gene approaches that the widely used human Glial Fibrillary Acidic Protein (hGFAP)-Cre transgene exhibits spontaneous germ-line recombination activity in leading to deletion in brain, heart and tail tissue with high frequency. The ectopic activity of hGFAP-Cre requires a rigorous control. We likewise observed that a second widely used nestin-Cre transgene shows germ-line deletion. Here we describe procedures to identify mice with germ-line recombination mediated by the hGFAP-Cre and nestin-Cre transgenes. Such control is essential to avoid pleiotropic effects due to germ-line deletion of loxP-flanked target genes and to maintain the CNS-restricted deletion status in transgenic mouse colonies. PMID:24349371

  9. Generation of a non-leaky heat shock-inducible Cre line for conditional Cre/lox strategies in zebrafish.

    PubMed

    Hans, Stefan; Freudenreich, Dorian; Geffarth, Michaela; Kaslin, Jan; Machate, Anja; Brand, Michael

    2011-01-01

    Cre-mediated site-specific recombination has emerged as an indispensable tool for the precise manipulation of the mammalian genome. Recently, we showed that Cre is also highly efficient in zebrafish and temporal control of recombination can be achieved by using the ligand-inducible CreER(T2). Previous attempts have been made to control recombination by using the temperature inducible hsp70l promoter to conditionally drive the expression of Cre or EGFP-Cre, respectively. However, in this study we demonstrate that the hsp70l promoter possesses a basal leakiness resulting in Cre-mediated recombination even at permissive temperatures. In order to prevent non-conditional recombination, we combined the hsp70l promoter with a mCherry-tagged ligand-inducible CreER(T2). At permissive temperatures and in the absence of the ligand tamoxifen (TAM), no non-conditional recombination is observed indicating tight regulation of CreER(T2). Instead, comprehensive site-specific recombination is mediated following heat induction and administration of TAM. © 2010 Wiley-Liss, Inc.

  10. Cre-mediated recombination in pituitary somatotropes

    PubMed Central

    Nasonkin, Igor O.; Potok, Mary Anne; Camper, Sally A.

    2009-01-01

    We report a transgenic line with highly penetrant cre recombinase activity in the somatotrope cells of the anterior pituitary gland. Expression of the cre transgene is under the control of the locus control region of the human growth hormone gene cluster and the rat growth hormone promoter. Cre recombinase activity was assessed with two different lacZ reporter genes that require excision of a floxed stop sequence for expression: a chick β-actin promoter with the CMV enhancer transgene and a ROSA26 knock-in. Cre activity is detectable in the developing pituitary after initiation of Gh transcription and persists through adulthood with high penetrance in Gh expressing cells and lower penetrance in lactotropes, a cell type that shares a common origin with somatotropes. This Gh-cre transgenic line is suitable for efficient, cell-specific deletion of floxed regions of genomic DNA in differentiated somatotropes and a subset of lactotrope cells of the anterior pituitary gland. PMID:19039787

  11. Risk Factors for Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) Acquisition Among Contacts of Newly Diagnosed CP-CRE Patients.

    PubMed

    Schwartz-Neiderman, Anat; Braun, Tali; Fallach, Noga; Schwartz, David; Carmeli, Yehuda; Schechner, Vered

    2016-10-01

    OBJECTIVE Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are extremely drug-resistant pathogens. Screening of contacts of newly identified CP-CRE patients is an important step to limit further transmission. We aimed to determine the risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient. METHODS A matched case-control study was performed in a tertiary care hospital in Israel. The study population was comprised of patients who underwent rectal screening for CP-CRE following close contact with a newly identified CP-CRE index patient. Cases were defined as positive tests for CP-CRE. For each case patient, 2 matched controls were randomly selected from the pool of contacts who tested negative for CP-CRE following exposure to the same index case. Bivariate and multivariate analyses were conducted using conditional logistic regression. RESULTS In total, 53 positive contacts were identified in 40 unique investigations (896 tests performed on 735 contacts) between October 6, 2008, and June 7, 2012. bla KPC was the only carbapenemase identified. In multivariate analysis, risk factors for CP-CRE acquisition among contacts were (1) contact with an index patient for ≥3 days (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.0-48.9), (2) mechanical ventilation (OR, 4.1; 95% CI, 1.4-11.9), and (3) carriage or infection with another multidrug-resistant organism (MDRO; OR, 2.6; 95% CI, 1.0-7.1). Among patients who received antibiotics, cephalosporins were associated with a lower risk of acquisition. CONCLUSIONS Patient characteristics (ventilation and carriage of another MDRO) as well as duration of contact are risk factors for CP-CRE acquisition among contacts. The role of cephalosporins requires further study. Infect Control Hosp Epidemiol 2016;1-7.

  12. A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre.

    PubMed

    Frutkin, Andrew D; Shi, Haikun; Otsuka, Goro; Levéen, Per; Karlsson, Stefan; Dichek, David A

    2006-10-01

    Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type II TGF-beta receptor (tgfbr2flox) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2flox. Surprisingly, SMMHC-Cre mice recombined tgfbr2flox at low levels in SMC and at high levels in the testis. Recombination of tgfbr2flox in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2null. In contrast, mice expressing Cre from a SM22alpha promoter (SM22-Cre) efficiently recombined tgfbr2flox in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2flox/flox zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2flox- and would have conversion of tgfbr2flox/flox to tgfbr2null/null in SMC-produced no live SM22-Cre : tgfbr2flox/flox pups (P<0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge.

  13. Increased production of biomass-degrading enzymes by double deletion of creA and creB genes involved in carbon catabolite repression in Aspergillus oryzae.

    PubMed

    Ichinose, Sakurako; Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2018-02-01

    In a previous study, we reported that a double gene deletion mutant for CreA and CreB, which constitute the regulatory machinery involved in carbon catabolite repression, exhibited improved production of α-amylase compared with the wild-type strain and single creA or creB deletion mutants in Aspergillus oryzae. Because A. oryzae can also produce biomass-degrading enzymes, such as xylolytic and cellulolytic enzymes, we examined the production levels of those enzymes in deletion mutants in this study. Xylanase and β-glucosidase activities in the wild-type were hardly detected in submerged culture containing xylose as the carbon source, whereas those enzyme activities were significantly increased in the single creA deletion (ΔcreA) and double creA and creB deletion (ΔcreAΔcreB) mutants. In particular, the ΔcreAΔcreB mutant exhibited >100-fold higher xylanase and β-glucosidase activities than the wild-type. Moreover, in solid-state culture, the β-glucosidase activity of the double deletion mutant was >7-fold higher than in the wild-type. These results suggested that deletion of both creA and creB genes could also efficiently improve the production levels of biomass-degrading enzymes in A. oryzae. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint

    PubMed Central

    Nagao, Masashi; Cheong, Chan Wook; Olsen, Bjorn

    2015-01-01

    Objective Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines. Methods We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points. Results In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endothelium and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium. Conclusions This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered. PMID:26256767

  15. Comprehensive Fund-Raising Campaigns: A Basic Guide for Governing Boards of Independent Institutions. Fund-Raising Topics. Board Basics.

    ERIC Educational Resources Information Center

    Schrum, Jake B., Ed.

    2001-01-01

    This guide for the governing boards of independent institutions discusses conducting a comprehensive fund-raising campaign. A comprehensive fund-raising campaign is broader and more strategic than past capital fund raising campaigns. Its financial goals include all potential gifts from annual fund donors, all gifts for the endowment, all gifts for…

  16. Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase.

    PubMed

    Lallemand, Y; Luria, V; Haffner-Krausz, R; Lonai, P

    1998-03-01

    A transgenic mouse strain with early and uniform expression of the Cre site-specific recombinase is described. In this strain, PGK-Crem, Cre is driven by the early acting PGK-1 promoter, but, probably due to cis effects at the integration site, the recombinase is under dominant maternal control. When Cre is transmitted by PGK-Crem females mated to males that carry a reporter transgene flanked by loxP sites, even offspring that do not inherit PGK-Cre delete the target gene. It follows that in the PGK-Crem female Cre activity commences in the diploid phase of oogenesis. In PGK-Crem crosses complete recombination was observed in all organs, including testis and ovary. We prepared a mouse stock that is homozygous for PGK-Crem and at the albino (c) locus. This strain will be useful for the early and uniform induction of ectopic and dominant negative mutations, for the in vivo removal of selective elements from targeted mutations and in connection with the manipulation of targeted loci in 'knock in' and related technologies.

  17. Building Cre Knockin Rat Lines Using CRISPR/Cas9.

    PubMed

    Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

    2017-01-01

    Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool. We have used CRISPR/Cas9 system to generate rat strains that carry Cre genes in different targeted gene loci by direct delivery of gRNAs/Cas9/donors into fertilized eggs. Here, we described a stepwise procedure for the generation of Cre knockin rat, including target site selection, RNA preparation, the construction of the template donor, pronuclear injection, and the genotyping of precise Cre insertion in F 0 rats. Taken together, the establishment of Cre knockin line can be achieved within 6 weeks.

  18. Heterogeneous transgene expression in the retinas of the TH-RFP, TH-Cre, TH-BAC-Cre and DAT-Cre mouse lines

    PubMed Central

    Vuong, Helen E.; de Sevilla Müller, Luis Pérez; Hardi, Claudia N.; McMahon, Douglas G.; Brecha, Nicholas C.

    2015-01-01

    Transgenic mouse lines are essential tools for understanding the connectivity, physiology and function of neuronal circuits, including those in the retina. This report compares transgene expression in the retina of a tyrosine hydroxylase (TH)-red fluorescent protein (RFP) line with three catecholamine-related Cre recombinase lines [TH-bacterial artificial chromosome (BAC)-, TH-, and dopamine transporter (DAT)-Cre] that were crossed with a ROSA26-tdTomato reporter line. Retinas were evaluated and immunostained with commonly used antibodies including those directed to TH, GABA and glycine to characterize the RFP or tdTomato fluorescent-labeled amacrine cells, and an antibody directed to RNA-binding protein with multiple splicing to identify ganglion cells. In TH-RFP retinas, types 1 and 2 dopamine (DA) amacrine cells were identified by their characteristic cellular morphology and type 1 DA cells by their expression of TH immunoreactivity. In the TH-BAC-, TH-, and DAT-tdTomato retinas, less than 1%, ~6%, and 0%, respectively, of the fluorescent cells were the expected type 1 DA amacrine cells. Instead, in the TH-BAC-tdTomato retinas, fluorescently labeled AII amacrine cells were predominant, with some medium somal diameter ganglion cells. In TH-tdTomato retinas, fluorescence was in multiple neurochemical amacrine cell types, including four types of polyaxonal amacrine cells. In DAT-tdTomato retinas, fluorescence was in GABA immunoreactive amacrine cells, including two types of bistratified and two types of monostratified amacrine cells. Although each of the Cre lines were generated with the intent to specifically label DA cells, our findings show a cellular diversity in Cre expression in the adult retina and indicate the importance of careful characterization of transgene labeling patterns. These mouse lines with their distinctive cellular labeling patterns will be useful tools for future studies of retinal function and visual processing. PMID:26335381

  19. Heterogeneous transgene expression in the retinas of the TH-RFP, TH-Cre, TH-BAC-Cre and DAT-Cre mouse lines.

    PubMed

    Vuong, H E; Pérez de Sevilla Müller, L; Hardi, C N; McMahon, D G; Brecha, N C

    2015-10-29

    Transgenic mouse lines are essential tools for understanding the connectivity, physiology and function of neuronal circuits, including those in the retina. This report compares transgene expression in the retina of a tyrosine hydroxylase (TH)-red fluorescent protein (RFP) mouse line with three catecholamine-related Cre recombinase mouse lines [TH-bacterial artificial chromosome (BAC)-, TH-, and dopamine transporter (DAT)-Cre] that were crossed with a ROSA26-tdTomato reporter line. Retinas were evaluated and immunostained with commonly used antibodies including those directed to TH, GABA and glycine to characterize the RFP or tdTomato fluorescent-labeled amacrine cells, and an antibody directed to RNA-binding protein with multiple splicing to identify ganglion cells. In TH-RFP retinas, types 1 and 2 dopamine (DA) amacrine cells were identified by their characteristic cellular morphology and type 1 DA cells by their expression of TH immunoreactivity. In the TH-BAC-, TH-, and DAT-tdTomato retinas, less than 1%, ∼ 6%, and 0%, respectively, of the fluorescent cells were the expected type 1 DA amacrine cells. Instead, in the TH-BAC-tdTomato retinas, fluorescently labeled AII amacrine cells were predominant, with some medium diameter ganglion cells. In TH-tdTomato retinas, fluorescence was in multiple neurochemical amacrine cell types, including four types of polyaxonal amacrine cells. In DAT-tdTomato retinas, fluorescence was in GABA immunoreactive amacrine cells, including two types of bistratified and two types of monostratified amacrine cells. Although each of the Cre lines was generated with the intent to specifically label DA cells, our findings show a cellular diversity in Cre expression in the adult retina and indicate the importance of careful characterization of transgene labeling patterns. These mouse lines with their distinctive cellular labeling patterns will be useful tools for future studies of retinal function and visual processing. Published by Elsevier

  20. The Sox17CreERT2 knock-in mouse line displays spatiotemporal activation of Cre recombinase in distinct Sox17 lineage progenitors.

    PubMed

    Engert, Silvia; Burtscher, Ingo; Kalali, Behnam; Gerhard, Markus; Lickert, Heiko

    2013-11-01

    The HMG-box transcription factor Sox17 is essential for endoderm formation, vascular development, and definitive hematopoiesis. To investigate the fate of distinct Sox17-expressing progenitor cells in a spatiotemporal manner, we generated a hormone-inducible CreERT2 knock-in mouse line. By homologous recombination we fused a codon improved, ligand-dependent estrogen receptor Cre recombinase by an intervening viral T2A sequence for co-translational cleavage to the 3' coding region of Sox17. Induction of Cre activity by administration of tamoxifen at defined time points of early mouse development and subsequent genetic lineage tracing confirmed the inducibility and tissue specificity of Cre recombination. Furthermore, Cre activity could be selectively induced in extra-embryonic and embryonic endoderm lineages, the primitive gut tube, and in endothelial cells of the vascular system as well as in the hemogenic endothelium of the dorsal aorta. The Sox17CreERT2 mouse line therefore represents a new tool for genetic lineage tracing in a tissue-specific manner and in addition enables lineage-restricted functional analysis. Copyright © 2013 Wiley Periodicals, Inc.

  1. Phenotypically silent Cre recombination within the postnatal ventricular conduction system.

    PubMed

    Bhattacharyya, Samadrita; Bhakta, Minoti; Munshi, Nikhil Vilas

    2017-01-01

    The cardiac conduction system (CCS) is composed of specialized cardiomyocytes that initiate and maintain cardiac rhythm. Any perturbation to the normal sequence of electrical events within the heart can result in cardiac arrhythmias. To understand how cardiac rhythm is established at the molecular level, several genetically modified mouse lines expressing Cre recombinase within specific CCS compartments have been created. In general, Cre driver lines have been generated either by homologous recombination of Cre into an endogenous locus or Cre expression driven by a randomly inserted transgene. However, haploinsufficiency of the endogenous gene compromises the former approach, while position effects negatively impact the latter. To address these limitations, we generated a Cre driver line for the ventricular conduction system (VCS) that preserves endogenous gene expression by targeting the Contactin2 (Cntn2) 3' untranslated region (3'UTR). Here we show that Cntn23'UTR-IRES-Cre-EGFP/+ mice recombine floxed alleles within the VCS and that Cre expression faithfully recapitulates the spatial distribution of Cntn2 within the heart. We further demonstrate that Cre expression initiates after birth with preservation of native Cntn2 protein. Finally, we show that Cntn23'UTR-IRES-Cre-EGFP/+ mice maintain normal cardiac mechanical and electrical function. Taken together, our results establish a novel VCS-specific Cre driver line without the adverse consequences of haploinsufficiency or position effects. We expect that our new mouse line will add to the accumulating toolkit of CCS-specific mouse reagents and aid characterization of the cell-autonomous molecular circuitry that drives VCS maintenance and function.

  2. Tg(Th-Cre)FI172Gsat (Th-Cre) defines neurons that are required for full hypercapnic and hypoxic reflexes.

    PubMed

    Sun, Jenny J; Ray, Russell S

    2017-08-15

    The catecholaminergic (CA) system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-Cre)FI172Gsat ( Th-Cre )-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO)-DREADD-mediated inhibition of Th-Cre -defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5% CO 2 /21% O 2 /74% N 2 ), perturbation of Th-Cre neurons results in reduced f R , [Formula: see text] and [Formula: see text] Under a hypoxic challenge (10% O 2 /90% N 2 ), we saw reduced f R , [Formula: see text] and [Formula: see text], in addition to instability in both interbreath interval and tidal volume, resulting in a Cheyne-Stokes-like respiratory pattern. These findings demonstrate the necessity of Th-Cre -defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-CA expression domains of the Tg(Th-Cre)FI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to CA neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges. © 2017. Published by The Company of Biologists Ltd.

  3. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    PubMed

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  4. Generation and characterization of Atoh1-Cre knock-in mouse line

    PubMed Central

    Yang, Hua; Xie, Xiaoling; Deng, Min; Chen, Xiaowei; Gan, Lin

    2010-01-01

    Summary Atoh1 encodes a basic helix-loop-helix (bHLH) transcription factor required for the development of the inner ear sensory epithelia, the dorsal spinal cord, brainstem, cerebellum, and intestinal secretory cells. In this study to create a genetic tool for the research on gene function in the ear sensory organs, we generated an Atoh1-Cre knock-in mouse line by replacing the entire Atoh1 coding sequences with the Cre coding sequences. Atoh1Cre/+mice were viable, fertile, and displayed no visible defects whereas the Atoh1Cre/Cremice died perinatally. The spatiotemporal activities of Cre recombinase were examined by crossing Atoh1-Cre mice with the R26R-lacZ conditional reporter mice. Atoh1-Cre activities were detected in the developing inner ear, the hindbrain, the spinal cord, and the intestine. In the inner ear, Atoh1-Cre activities were confined to the sensory organs in which lacZ expression is detected in nearly all of the hair cells and in many supporting cells. Thus, Atoh1-Cre mouse line serves as a useful tool for the functional study of genes in the inner ear. In addition, our results demonstrate that Atoh1 is expressed in the common progenitors destined for both hair and supporting cells. PMID:20533400

  5. Cell Type-Specific Manipulation with GFP-Dependent Cre Recombinase

    PubMed Central

    Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S; Abraira, Victoria E; Choi, Seungwon; Lapan, Sylvain; Drew, Iain R; Drokhlyansky, Eugene; Huberman, Andrew D; Regehr, Wade G; Cepko, Constance L

    2016-01-01

    Summary There are many transgenic GFP reporter lines that allow visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. Here we report the creation of a method that exploits GFP for gene manipulation, Cre Recombinase Dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, leading to effective recombination selectively in GFP-labeled cells. Further, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP+ cells, we demonstrate that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins. PMID:26258682

  6. Cell type-specific manipulation with GFP-dependent Cre recombinase.

    PubMed

    Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S; Abraira, Victoria E; Choi, Seungwon; Lapan, Sylvain W; Drew, Iain R; Drokhlyansky, Eugene; Huberman, Andrew D; Regehr, Wade G; Cepko, Constance L

    2015-09-01

    There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.

  7. The Effect of Conditional Inactivation of Beta 1 Integrins using Twist 2 Cre, Osterix Cre and Osteocalcin Cre Lines on Skeletal Phenotype

    PubMed Central

    Shekaran, Asha; Shoemaker, James T.; Kavanaugh, Taylor E.; Lin, Angela S.; LaPlaca, Michelle C.; Fan, Yuhong; Guldberg, Robert E.; García, Andrés J.

    2014-01-01

    Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and Osteocalcin-Cre lines to generate conditional β1 integrin deletions, where cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic

  8. Dwarfism in homozygous Agc1CreERT mice is associated with decreased expression of aggrecan.

    PubMed

    Rashid, Harunur; Chen, Haiyan; Hassan, Quamarul; Javed, Amjad

    2017-10-01

    Aggrecan (Acan), a large proteoglycan is abundantly expressed in cartilage tissue. Disruption of Acan gene causes dwarfism and perinatal lethality of homozygous mice. Because of sustained expression of Acan in the growth plate and articular cartilage, Agc Cre model has been developed for the regulated ablation of target gene in chondrocytes. In this model, the IRES-CreERT-Neo-pgk transgene is knocked-in the 3'UTR of the Acan gene. We consistently noticed variable weight and size among the Agc Cre littermates, prompting us to examine the cause of this phenotype. Wild-type, Cre-heterozygous (Agc +/Cre ), and Cre-homozygous (Agc Cre/Cre ) littermates were indistinguishable at birth. However, by 1-month, Agc Cre/Cre mice showed a significant reduction in body weight (18-27%) and body length (19-22%). Low body weight and dwarfism was sustained through adulthood and occurred in both genders. Compared with wild-type and Agc +/Cre littermates, long bones and vertebrae were shorter in Agc Cre/Cre mice. Histological analysis of Agc Cre/Cre mice revealed a significant reduction in the length of the growth plate and the thickness of articular cartilage. The amount of proteoglycan deposited in the cartilage of Agc Cre/Cre mice was nearly half of the WT littermates. Analysis of gene expression indicates impaired differentiation of chondrocyte in hyaline cartilage of Agc Cre/Cre mice. Notably, both Acan mRNA and protein was reduced by 50% in Agc Cre/Cre mice. A strong correlation was noted between the level of Acan mRNA and the body length. Importantly, Agc +/Cre mice showed no overt skeletal phenotype. Thus to avoid misinterpretation of data, only the Agc +/Cre mice should be used for conditional deletion of a target gene in the cartilage tissue. © 2017 Wiley Periodicals, Inc.

  9. Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice.

    PubMed

    Runegaard, Annika H; Jensen, Kathrine L; Fitzpatrick, Ciarán M; Dencker, Ditte; Weikop, Pia; Gether, Ulrik; Rickhag, Mattias

    2017-01-01

    Cre-driver mouse lines have been extensively used as genetic tools to target and manipulate genetically defined neuronal populations by expression of Cre recombinase under selected gene promoters. This approach has greatly advanced neuroscience but interpretations are hampered by the fact that most Cre-driver lines have not been thoroughly characterized. Thus, a phenotypic characterization is of major importance to reveal potential aberrant phenotypes prior to implementation and usage to selectively inactivate or induce transgene expression. Here, we present a biochemical and behavioural assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice also show preserved dopamine transporter expression and function supporting sustained dopaminergic transmission. In addition, TH-Cre mice demonstrate normal responses in basic behavioural paradigms related to dopaminergic signalling including locomotor activity, reward preference and anxiolytic behaviour. Our results suggest that TH-Cre mice represent a valid tool to study the dopamine system, though careful characterization must always be performed to prevent false interpretations following Cre-dependent transgene expression and manipulation of selected neuronal pathways. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Stoichiometry of the Cre recombinase bound to the lox recombining site.

    PubMed Central

    Mack, A; Sauer, B; Abremski, K; Hoess, R

    1992-01-01

    The site-specific recombinase Cre from bacteriophage P1 binds and carries out recombination at a 34 bp lox site. The lox site consists of two 13 bp inverted repeats, separated by an 8 bp spacer region. Both the palindromic nature of the site and the results of footprinting and band shift experiments suggest that a minimum of two Cre molecules bind to a lox site. We report here experiments that demonstrate the absolute stoichiometry of the Cre-lox complex to be one molecule of Cre bound per inverted repeat, or two molecules per lox site. Images PMID:1408747

  11. Regulation of Cre recombinase by ligand-induced complementation of inactive fragments.

    PubMed

    Jullien, Nicolas; Sampieri, François; Enjalbert, Alain; Herman, Jean-Paul

    2003-11-01

    Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. To overcome this, we have developed DiCre, a regulatable fragment complementation system for Cre. The enzyme was split into two moieties that were fused to FKBP12 (FK506-binding protein) and FRB (binding domain of the FKBP12-rapamycin-associated protein), respectively. These can be efficiently heterodimerized by rapamycin. Several variants, based on splitting Cre at different sites and using different linker peptides, were tested in an indicator cell line. The fusion proteins, taken separately, had no recombinase activity. Stable transformants, co-expressing complementing fragments based on splitting Cre between Asn59 and Asn60, displayed low background activity affecting 0.05-0.4% of the cells. Rapamycin induced a rapid recombination, reaching 100% by 48-72 h, with an EC50 of 0.02 nM. Thus, ligand-induced dimerization can efficiently regulate Cre, and should be useful to achieve a tight temporal control of its activity, such as in the case of the creation of conditional knock-out animals.

  12. Cre recombinase-mediated site-specific recombination between plant chromosomes.

    PubMed Central

    Qin, M; Bayley, C; Stockton, T; Ow, D W

    1994-01-01

    We report the use of the bacteriophage P1 Cre-lox system for generating conservative site-specific recombination between tobacco chromosomes. Two constructs, one containing a promoterless hygromycin-resistance gene preceded by a lox site (lox-hpt) and the other containing a cauliflower mosaic virus 35S promoter linked to a lox sequence and the cre coding region (35S-lox-cre), were introduced separately into tobacco plants. Crosses between plants harboring either construct produced plants with the two constructs situated on different chromosomes. Plants with recombination events were identified by selecting for hygromycin resistance, a phenotype expressed upon recombination. Molecular analysis showed that these recombination events occurred specifically at the lox sites and resulted in the reciprocal exchange of flanking host DNA. Progenies of these plants showed 67-100% cotransmission of the new transgenes, 35S-lox-hpt and lox-cre, consistent with the preferential cosegregation of translocated chromosomes. These results illustrate that site-specific recombination systems can be useful tools for the large-scale manipulation of eukaryotic chromosomes in vivo. Images PMID:8127869

  13. Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1 CreERT2 and Glast CreERT2 Murine Lines.

    PubMed

    Yang, Sung M; Alvarez, Diego D; Schinder, Alejandro F

    2015-11-18

    Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs. In this work, we used genetically modified mice to allow conditional expression of tdTomato (Tom) in adult-born GCs and characterized their development and functional integration. Ascl1(CreERT2);CAG(floxStopTom) and Glast(CreERT2);CAG(floxStopTom) mice resulted in indelible expression of Tom in adult neural stem cells and their lineage upon tamoxifen induction. Whole-cell recordings were performed to measure intrinsic excitability, firing behavior, and afferent excitatory connectivity. Developing GCs were also staged by the expression of early and late neuronal markers. The slow development of adult-born GCs characterized here is consistent with previous reports using retroviral approaches that have revealed that a mature phenotype is typically achieved after 6-8 weeks. Our findings demonstrate that Ascl1(CreERT2) and Glast(CreERT2) mouse lines enable simple and reliable labeling of adult-born GC lineages within restricted time windows. Therefore, these mice greatly facilitate tagging new neurons and manipulating their activity, required for understanding adult neurogenesis in the context of network remodeling, learning, and behavior. Our study shows that Ascl1(CreERT2) and Glast(CreERT2) mice lines can be used to label large cohorts of adult-born dentate granule cells with excellent time resolution. Neurons labeled in this manner display developmental and functional profiles that are in full agreement with previous findings using thymidine analogs and retroviral labeling, thus providing an alternative approach to tackle fundamental questions on circuit remodeling. Because of the massive neuronal targeting and the simplicity of this method, genetic labeling will

  14. A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

    ClinicalTrials.gov

    2016-10-03

    Bloodstream Infections (BSI) Due to CRE; Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE; Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE; Complicated Urinary Tract Infection (cUTI) Due to CRE; Acute Pyelonephritis (AP) Due to CRE

  15. Isolation of Novel CreERT2-Driver Lines in Zebrafish Using an Unbiased Gene Trap Approach

    PubMed Central

    Jungke, Peggy; Hammer, Juliane; Hans, Stefan; Brand, Michael

    2015-01-01

    Gene manipulation using the Cre/loxP-recombinase system has been successfully employed in zebrafish to study gene functions and lineage relationships. Recently, gene trapping approaches have been applied to produce large collections of transgenic fish expressing conditional alleles in various tissues. However, the limited number of available cell- and tissue-specific Cre/CreERT2-driver lines still constrains widespread application in this model organism. To enlarge the pool of existing CreERT2-driver lines, we performed a genome-wide gene trap screen using a Tol2-based mCherry-T2a-CreERT2 (mCT2aC) gene trap vector. This cassette consists of a splice acceptor and a mCherry-tagged variant of CreERT2 which enables simultaneous labeling of the trapping event, as well as CreERT2 expression from the endogenous promoter. Using this strategy, we generated 27 novel functional CreERT2-driver lines expressing in a cell- and tissue-specific manner during development and adulthood. This study summarizes the analysis of the generated CreERT2-driver lines with respect to functionality, expression, integration, as well as associated phenotypes. Our results significantly enlarge the existing pool of CreERT2-driver lines in zebrafish and combined with Cre–dependent effector lines, the new CreERT2-driver lines will be important tools to manipulate the zebrafish genome. PMID:26083735

  16. Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines.

    PubMed

    Chen, Edison; Lallai, Valeria; Sherafat, Yasmine; Grimes, Nickolas P; Pushkin, Anna N; Fowler, J P; Fowler, Christie D

    2018-02-28

    The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT (BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT (IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT (BAC) -Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT (BAC) -Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT (IRES) -Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT (IRES) -Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT (IRES) -Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT (IRES) -Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations. SIGNIFICANCE STATEMENT Altered

  17. Single-neuron labeling with inducible cre-mediated knockout in transgenic mice

    PubMed Central

    Young, Paul; Qiu, Li; Wang, Dongqing; Zhao, Shengli; Gross, James; Feng, Guoping

    2011-01-01

    To facilitate functional analysis of neuronal connectivity in a mammalian nervous system tightly packed with billions of cells, we developed a new technique that allows inducible genetic manipulations within fluorescently labeled single neurons in mice. We term this technique SLICK for Single-neuron Labeling with Inducible Cre-mediated Knockout. SLICK is achieved by co-expressing a drug-inducible form of cre recombinase and a fluorescent protein within the same small subsets of neurons. Thus, SLICK combines the powerful cre recombinase system for conditional genetic manipulation and the fluorescent labeling of single neurons for imaging. We demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we apply SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals. More broadly, these studies demonstrate a cre-LoxP compatible system for dissecting gene functions in single identifiable neurons. PMID:18454144

  18. Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice

    PubMed Central

    Winchenbach, Jan; Düking, Tim; Berghoff, Stefan A.; Stumpf, Sina K.; Hülsmann, Swen; Nave, Klaus-Armin; Saher, Gesine

    2016-01-01

    Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions. PMID:28149504

  19. Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice.

    PubMed

    Winchenbach, Jan; Düking, Tim; Berghoff, Stefan A; Stumpf, Sina K; Hülsmann, Swen; Nave, Klaus-Armin; Saher, Gesine

    2016-01-01

    Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.

  20. Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States.

    PubMed

    Bartsch, S M; McKinnell, J A; Mueller, L E; Miller, L G; Gohil, S K; Huang, S S; Lee, B Y

    2017-01-01

    The Centers for Disease Control and Prevention considers carbapenem-resistant Enterobacteriaceae (CRE) an urgent public health threat; however, its economic burden is unknown. We developed a CRE clinical and economics outcomes model to determine the cost of CRE infection from the hospital, third-party payer, and societal, perspectives and to evaluate the health and economic burden of CRE to the USA. Depending on the infection type, the median cost of a single CRE infection can range from $22 484 to $66 031 for hospitals, $10 440 to $31 621 for third-party payers, and $37 778 to $83 512 for society. An infection incidence of 2.93 per 100 000 population in the USA (9418 infections) would cost hospitals $275 million (95% CR $217-334 million), third-party payers $147 million (95% CR $129-172 million), and society $553 million (95% CR $303-1593 million) with a 25% attributable mortality, and would result in the loss of 8841 (95% CR 5805-12 420) quality-adjusted life years. An incidence of 15 per 100 000 (48 213 infections) would cost hospitals $1.4 billion (95% CR $1.1-1.7 billion), third-party payers $0.8 billion (95% CR $0.6-0.8 billion), and society $2.8 billion (95% CR $1.6-8.2 billion), and result in the loss of 45 261 quality-adjusted life years. The cost of CRE is higher than the annual cost of many chronic diseases and of many acute diseases. Costs rise proportionally with the incidence of CRE, increasing by 2.0 times, 3.4 times, and 5.1 times for incidence rates of 6, 10, and 15 per 100 000 persons. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. A Novel Dual-cre Motif Enables Two-Way Autoregulation of CcpA in Clostridium acetobutylicum.

    PubMed

    Zhang, Lu; Liu, Yanqiang; Yang, Yunpeng; Jiang, Weihong; Gu, Yang

    2018-04-15

    The master regulator CcpA (catabolite control protein A) manages a large and complex regulatory network that is essential for cellular physiology and metabolism in Gram-positive bacteria. Although CcpA can affect the expression of target genes by binding to a cis -acting catabolite-responsive element ( cre ), whether and how the expression of CcpA is regulated remain poorly explored. Here, we report a novel dual- cre motif that is employed by the CcpA in Clostridium acetobutylicum , a typical solventogenic Clostridium species, for autoregulation. Two cre sites are involved in CcpA autoregulation, and they reside in the promoter and coding regions of CcpA. In this dual- cre motif, cre P , in the promoter region, positively regulates ccpA transcription, whereas cre ORF , in the coding region, negatively regulates this transcription, thus enabling two-way autoregulation of CcpA. Although CcpA bound cre P more strongly than cre ORF in vitro , the in vivo assay showed that cre ORF -based repression dominates CcpA autoregulation during the entire fermentation. Finally, a synonymous mutation of cre ORF was made within the coding region, achieving an increased intracellular CcpA expression and improved cellular performance. This study provides new insights into the regulatory role of CcpA in C. acetobutylicum and, moreover, contributes a new engineering strategy for this industrial strain. IMPORTANCE CcpA is known to be a key transcription factor in Gram-positive bacteria. However, it is still unclear whether and how the intracellular CcpA level is regulated, which may be essential for maintaining normal cell physiology and metabolism. We discovered here that CcpA employs a dual- cre motif to autoregulate, enabling dynamic control of its own expression level during the entire fermentation process. This finding answers the questions above and fills a void in our understanding of the regulatory network of CcpA. Interference in CcpA autoregulation leads to improved cellular

  2. High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting.

    PubMed

    Ackermann, Amanda M; Zhang, Jia; Heller, Aryel; Briker, Anna; Kaestner, Klaus H

    2017-03-01

    α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells. Previous Glucagon-Cre and Glucagon-CreER transgenic mouse lines have suffered from transgene silencing, and the only available Glucagon-CreER "knock-in" mouse line results in glucagon haploinsufficiency, which can confound the interpretation of gene deletion analyses. Therefore, we sought to develop a Glucagon-CreER T2 mouse line that would maintain normal glucagon expression and would be less susceptible to transgene silencing. We utilized CRISPR-Cas9 technology to insert an IRES-CreER T2 sequence into the 3' UTR of the Glucagon ( Gcg ) locus in mouse embryonic stem cells (ESCs). Targeted ESC clones were then injected into mouse blastocysts to obtain Gcg-CreER T2 mice. Recombination efficiency in GCG + pancreatic α-cells and glucagon-like peptide 1 positive (GLP1 + ) enteroendocrine L-cells was measured in Gcg-CreER T2 ; Rosa26-LSL-YFP mice injected with tamoxifen during fetal development and adulthood. Tamoxifen injection of Gcg-CreER T2 ; Rosa26-LSL-YFP mice induced high recombination efficiency of the Rosa26-LSL-YFP locus in perinatal and adult α-cells (88% and 95%, respectively), as well as in first-wave fetal α-cells (36%) and adult enteroendocrine L-cells (33%). Mice homozygous for the Gcg-CreER T2 allele were phenotypically normal. We successfully derived a Gcg-CreER T2 mouse line that expresses CreER T2 in pancreatic α-cells and enteroendocrine L-cells without disrupting preproglucagon gene expression. These mice will be a useful tool for performing

  3. Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

    PubMed

    Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

    2018-04-01

    Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

  4. Silencing Inhibits Cre-Mediated Recombination of the Z/AP and Z/EG Reporters in Adult Cells

    PubMed Central

    Long, Michael A.; Rossi, Fabio M. V.

    2009-01-01

    Background The Cre-loxP system has been used to enable tissue specific activation, inactivation and mutation of many genes in vivo and has thereby greatly facilitated the genetic dissection of several cellular and developmental processes. In such studies, Cre-reporter strains, which carry a Cre-activated marker gene, are frequently utilized to validate the expression profile of Cre transgenes, to act as a surrogate marker for excision of a second allele, and to irreversibly label cells for lineage tracing experiments. Principal Findings We have studied three commonly used Cre-reporter strains, Z/AP, Z/EG and R26R-EYFP and have demonstrated that although each reporter can be reliably activated by Cre during early development, exposure to Cre in adult hematopoietic cells results in a much lower frequency of marker-positive cells in the Z/AP or Z/EG strains than in the R26R-EYFP strain. In marker negative cells derived from the Z/AP and Z/EG strains, the transgenic promoter is methylated and Cre-mediated recombination of the locus is inhibited. Conclusions These results show that the efficiency of Cre-mediated recombination is not only dependent on the genomic context of a given loxP-flanked sequence, but also on stochastic epigenetic mechanisms underlying transgene variegation. Furthermore, our data highlights the potential shortcomings of utilizing the Z/AP and Z/EG reporters as surrogate markers of excision or in lineage tracing experiments. PMID:19415111

  5. Silencing inhibits Cre-mediated recombination of the Z/AP and Z/EG reporters in adult cells.

    PubMed

    Long, Michael A; Rossi, Fabio M V

    2009-01-01

    The Cre-loxP system has been used to enable tissue specific activation, inactivation and mutation of many genes in vivo and has thereby greatly facilitated the genetic dissection of several cellular and developmental processes. In such studies, Cre-reporter strains, which carry a Cre-activated marker gene, are frequently utilized to validate the expression profile of Cre transgenes, to act as a surrogate marker for excision of a second allele, and to irreversibly label cells for lineage tracing experiments. We have studied three commonly used Cre-reporter strains, Z/AP, Z/EG and R26R-EYFP and have demonstrated that although each reporter can be reliably activated by Cre during early development, exposure to Cre in adult hematopoietic cells results in a much lower frequency of marker-positive cells in the Z/AP or Z/EG strains than in the R26R-EYFP strain. In marker negative cells derived from the Z/AP and Z/EG strains, the transgenic promoter is methylated and Cre-mediated recombination of the locus is inhibited. These results show that the efficiency of Cre-mediated recombination is not only dependent on the genomic context of a given loxP-flanked sequence, but also on stochastic epigenetic mechanisms underlying transgene variegation. Furthermore, our data highlights the potential shortcomings of utilizing the Z/AP and Z/EG reporters as surrogate markers of excision or in lineage tracing experiments.

  6. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    PubMed Central

    Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta; Kiehn, Ole

    2017-01-01

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion. PMID:28128321

  7. Genome Engineering in Bacillus anthracis Using Cre Recombinase

    PubMed Central

    Pomerantsev, Andrei P.; Sitaraman, Ramakrishnan; Galloway, Craig R.; Kivovich, Violetta; Leppla, Stephen H.

    2006-01-01

    Genome engineering is a powerful method for the study of bacterial virulence. With the availability of the complete genomic sequence of Bacillus anthracis, it is now possible to inactivate or delete selected genes of interest. However, many current methods for disrupting or deleting more than one gene require use of multiple antibiotic resistance determinants. In this report we used an approach that temporarily inserts an antibiotic resistance marker into a selected region of the genome and subsequently removes it, leaving the target region (a single gene or a larger genomic segment) permanently mutated. For this purpose, a spectinomycin resistance cassette flanked by bacteriophage P1 loxP sites oriented as direct repeats was inserted within a selected gene. After identification of strains having the spectinomycin cassette inserted by a double-crossover event, a thermo-sensitive plasmid expressing Cre recombinase was introduced at the permissive temperature. Cre recombinase action at the loxP sites excised the spectinomycin marker, leaving a single loxP site within the targeted gene or genomic segment. The Cre-expressing plasmid was then removed by growth at the restrictive temperature. The procedure could then be repeated to mutate additional genes. In this way, we sequentially mutated two pairs of genes: pepM and spo0A, and mcrB and mrr. Furthermore, loxP sites introduced at distant genes could be recombined by Cre recombinase to cause deletion of large intervening regions. In this way, we deleted the capBCAD region of the pXO2 plasmid and the entire 30 kb of chromosomal DNA between the mcrB and mrr genes, and in the latter case we found that the 32 intervening open reading frames were not essential to growth. PMID:16369025

  8. Targeted transgene insertion into the CHO cell genome using Cre recombinase-incorporating integrase-defective retroviral vectors.

    PubMed

    Kawabe, Yoshinori; Shimomura, Takuya; Huang, Shuohao; Imanishi, Suguru; Ito, Akira; Kamihira, Masamichi

    2016-07-01

    Retroviral vectors have served as efficient gene delivery tools in various biotechnology fields. However, viral DNA is randomly inserted into the genome, which can cause problems, such as insertional mutagenesis and gene silencing. Previously, we reported a site-specific gene integration system, in which a transgene is integrated into a predetermined chromosomal locus of Chinese hamster ovary (CHO) cells using integrase-defective retroviral vectors (IDRVs) and Cre recombinase. In this system, a Cre expression plasmid is transfected into founder cells before retroviral transduction. In practical applications of site-specific gene modification such as for hard-to-transfect cells or for in vivo gene delivery, both the transgene and the Cre protein into retroviral virions should be encapsulate. Here, we generated novel hybrid IDRVs in which viral genome and enzymatically active Cre can be delivered (Cre-IDRVs). Cre-IDRVs encoding marker genes, neomycin resistance and enhanced green fluorescent protein (EGFP), flanked by wild-type and mutated loxP sites were produced using an expression plasmid for a chimeric protein of Cre and retroviral gag-pol. After analyzing the incorporation of the Cre protein into retroviral virions by Western blotting, the Cre-IDRV was infected into founder CHO cells, in which marker genes (hygromycin resistance and red fluorescent protein) flanked with corresponding loxP sites are introduced into the genome. G418-resistant colonies expressing GFP appeared and the site-specific integration of the transgene into the expected chromosomal site was confirmed by PCR and sequencing of amplicons. Moreover, when Cre-IDRV carried a gene expression unit for a recombinant antibody, the recombinant cells in which the antibody expression cassette was integrated in a site-specific manner were generated and the cells produced the recombinant antibody. This method may provide a promising tool to perform site-specific gene modification according to Cre

  9. Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

    PubMed

    Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M

    2013-09-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.

  10. Deletion of creB in Aspergillus oryzae Increases Secreted Hydrolytic Enzyme Activity

    PubMed Central

    Hunter, A. J.; Morris, T. A.; Jin, B.; Saint, C. P.

    2013-01-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes. PMID:23835170

  11. Disruption of Trichoderma reesei cre2, encoding an ubiquitin C-terminal hydrolase, results in increased cellulase activity

    PubMed Central

    2011-01-01

    Background The filamentous fungus Trichoderma reesei (Hypocrea jecorina) is an important source of cellulases for use in the textile and alternative fuel industries. To fully understand the regulation of cellulase production in T. reesei, the role of a gene known to be involved in carbon regulation in Aspergillus nidulans, but unstudied in T. reesei, was investigated. Results The T. reesei orthologue of the A. nidulans creB gene, designated cre2, was identified and shown to be functional through heterologous complementation of a creB mutation in A. nidulans. A T. reesei strain was constructed using gene disruption techniques that contained a disrupted cre2 gene. This strain, JKTR2-6, exhibited phenotypes similar to the A. nidulans creB mutant strain both in carbon catabolite repressing, and in carbon catabolite derepressing conditions. Importantly, the disruption also led to elevated cellulase levels. Conclusions These results demonstrate that cre2 is involved in cellulase expression. Since the disruption of cre2 increases the amount of cellulase activity, without severe morphological affects, targeting creB orthologues for disruption in other industrially useful filamentous fungi, such as Aspergillus oryzae, Trichoderma harzianum or Aspergillus niger may also lead to elevated hydrolytic enzyme activity in these species. PMID:22070776

  12. Molecular switch of Cre/loxP for radiation modulated gene therapy on hepatoma

    NASA Astrophysics Data System (ADS)

    Hsieh, Ya-Ju; Chen, Fu-Du; Wang, Fu Hui; Ke, Chien Chih; Wang, Hsin-Ell; Liu, Ren-Shyan

    2007-02-01

    For the purpose of enhancement of AFP promoter for the use of radiation modulated gene therapy for hepatocellular carcinoma (HCC), we combined hepatitis B virus (HBV) enhancer II with AFP promoter which shows the selectivity to the target cells to control the Cre/loxP system. Different gene constructs, pE4luc, pE4Tk, EIIAPA-Cre, E4CMV-STOP-Tk and chimeric promoters combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines. Cell experiments revealed that E4 enhancer responses to radiation best after 60 h irradiation at a dose range of 5-7 Gy in HepG2 stable clone. The EIIAPA promoter provided high specificity to hepatoma and activated the Cre downstream and removed the stop cassette only in hepatoma cells. After removal of the stop cassette, the E4 response to radiation could encode more Tk protein and kill more tumor cells. In summary, the chimeric EIIAPA promoter can stringently control the expression of Cre recombinase only in HCC. The radiation effect of the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of HCC.

  13. CDC Vital Signs: Making Health Care Safer -- Stop Infections from Lethal CRE Germs Now

    MedlinePlus

    ... recommendations when treating patients with CRE. Dedicate rooms, staff, and equipment to patients with CRE. Prescribe antibiotics ... coordinated, and consistent effort by doctors, nurses, lab staff, medical facility leadership, health departments/states, policy makers, ...

  14. Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities.

    PubMed

    Nagase, Hiroyuki; Omae, Naoki; Omori, Akiko; Nakagawasai, Osamu; Tadano, Takeshi; Yokosuka, Akihito; Sashida, Yutaka; Mimaki, Yoshihiro; Yamakuni, Tohru; Ohizumi, Yasushi

    2005-12-02

    cAMP response element (CRE) transcription is dysregulated in neurodegenerative disorders in the central nervous system (CNS), including polyglutamine diseases. As the first step to find natural compounds with protective action against neurodegeneration in the CNS, we here examined whether six citrus flavonoids, namely nobiletin, 5-demethylnobiletin, tangeretin, sinensetin, 6-demethoxytangeretin, and 6-demethoxynobiletin, stimulated CRE-dependent transcription and induced neurite outgrowth in PC12D cells. Among the compounds, nobiletin most potently enhanced CRE-dependent transcription and neurite outgrowth by activating ERK/MAP kinase-dependent signalling to increase CREB phosphorylation. The transcription and neurite outgrowth were stimulated by nobiletin in a concentration-dependent manner, with a strong correlation between them. Furthermore, a 11-day oral administration of nobiletin rescued impaired memory in olfactory-bulbectomized mice documented to be accompanied by a cholinergic neurodegeneration. These results suggest that nobiletin with the activity to improve impaired memory may become a potential leading compound for drug development for neurodegenerative disorders exhibiting the dysregulated CRE-dependent transcription.

  15. Strategic Plan for Higher Education, 2008-2017

    ERIC Educational Resources Information Center

    Fingerhut, Eric D.

    2008-01-01

    If the State of Ohio is to grow and prosper, it must raise the education level of its population. The goal of this 10-year strategic plan is to raise the educational attainment of the state each year, and to close the gap between Ohio and competitor states and nations. To accomplish this goal, stakeholders must do three things: (1) Graduate more…

  16. Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

    PubMed

    Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

    2017-06-01

    SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

  17. Overlapping ETS and CRE Motifs (G/CCGGAAGTGACGTCA) Preferentially Bound by GABPα and CREB Proteins

    PubMed Central

    Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Shlyakhtenko, Andrey; Mann, Ishminder; Waterfall, Joshua J.; Meltzer, Paul; Sathyanarayana, B. K.; FitzGerald, Peter C.; Vinson, Charles

    2012-01-01

    Previously, we identified 8-bps long DNA sequences (8-mers) that localize in human proximal promoters and grouped them into known transcription factor binding sites (TFBS). We now examine split 8-mers consisting of two 4-mers separated by 1-bp to 30-bps (X4-N1-30-X4) to identify pairs of TFBS that localize in proximal promoters at a precise distance. These include two overlapping TFBS: the ETS⇔ETS motif (C/GCCGGAAGCGGAA) and the ETS⇔CRE motif (C/GCGGAAGTGACGTCAC). The nucleotides in bold are part of both TFBS. Molecular modeling shows that the ETS⇔CRE motif can be bound simultaneously by both the ETS and the B-ZIP domains without protein-protein clashes. The electrophoretic mobility shift assay (EMSA) shows that the ETS protein GABPα and the B-ZIP protein CREB preferentially bind to the ETS⇔CRE motif only when the two TFBS overlap precisely. In contrast, the ETS domain of ETV5 and CREB interfere with each other for binding the ETS⇔CRE. The 11-mer (CGGAAGTGACG), the conserved part of the ETS⇔CRE motif, occurs 226 times in the human genome and 83% are in known regulatory regions. In vivo GABPα and CREB ChIP-seq peaks identified the ETS⇔CRE as the most enriched motif occurring in promoters of genes involved in mRNA processing, cellular catabolic processes, and stress response, suggesting that a specific class of genes is regulated by this composite motif. PMID:23050235

  18. Empirical Questionnaire Methods for Fund-Raising Campaign Preparedness in Extension

    ERIC Educational Resources Information Center

    Comley Adams, Catherine; Butler, Douglass A.

    2017-01-01

    Amid waning public financial support for Extension program offerings, highly strategic and professional fund-raising practices are necessary for gaining momentum among private philanthropists and closing the fiscal gap. University of Missouri Extension conducted a precampaign survey that invited feedback from stakeholders to inform Extension…

  19. Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast.

    PubMed

    Dacquin, Romain; Starbuck, Michael; Schinke, Thorsten; Karsenty, Gérard

    2002-06-01

    Cell- and time-specific gene inactivation should enhance our knowledge of bone biology. Implementation of this technique requires construction of transgenic mouse lines expressing Cre recombinase in osteoblasts, the bone forming cell. We tested several promoter fragments for their ability to drive efficient Cre expression in osteoblasts. In the first mouse transgenic line, the Cre gene was placed under the control of the 2.3-kb proximal fragment of the alpha1(I)-collagen promoter, which is expressed at high levels in osteoblasts throughout their differentiation. Transgenic mice expressing this transgene in bone were bred with the ROSA26 reporter (R26R) strain in which the ROSA26 locus is targeted with a conditional LacZ reporter cassette. In R26R mice, Cre expression and subsequent Cre-mediated recombination lead to expression of the LacZ reporter gene, an event that can be monitored by LacZ staining. LacZ staining was detected in virtually all osteoblasts of alpha1(I)-Cre;R26R mice indicating that homologous recombination occurred in these cells. No other cell type stained blue. In the second line studied, the 1.3-kb fragment of osteocalcin gene 2 (OG2) promoter, which is active in differentiated osteoblasts, was used to drive Cre expression. OG2-Cre mice expressed Cre specifically in bone. However, cross of OG2-Cre mice with R26R mice did not lead to any detectable LacZ staining in osteoblasts. Lastly, we tested a more active artificial promoter derived from the OG2 promoter. The artificial OG2-Cre transgene was expressed by reverse transcriptase-polymerase chain reaction in cartilage and bone samples. After cross of the artificial OG2-Cre mice with R26R mice, we detected a LacZ staining in articular chondrocytes but not in osteoblasts. Our data suggest that the only promoter able to drive Cre expression at a level sufficient to induce recombination in osteoblasts is the alpha1(I)-collagen promoter. Copyright 2002 Wiley-Liss, Inc.

  20. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    PubMed

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.

  1. Utility of HoxB2 enhancer-mediated Cre activity for functional studies in the developing inner ear.

    PubMed

    Szeto, Irene Y Y; Leung, Keith K H; Sham, Mai Har; Cheah, Kathryn S E

    2009-06-01

    The rhombomere 4(r4)-restricted expression of the mouse Hoxb2 gene is regulated by a 1.4-kb enhancer-containing fragment. Here, we showthat transgenic mouse lines expressing cre driven by this fragment (B2-r4-Cre), activated the R26R Cre reporter in rhombomere 4 and the second branchial arch, the epithelium of the first branchial arch, apical ectodermal ridge of the limb buds and the tail region. Of particular interest is Cre activity in the developing inner ear. Cre activity was found in the preotic field and otic placode at E8.5 and otocyst at E9.5-E12.5, in the cochleovestibular and facio-acoustic ganglia at E10.5 and the vestibular and spiral ganglia and all the otic epithelia derived from the otocyst at E15.5 and P0. Our data suggest that the B2-r4-Cre transgenic mice provide an important tool for conditional gene manipulation and lineage tracing in the inner ear. In combination with other transgenic lines expressing cre exclusively in the otic vesicle, the relative contributions of the hindbrain, periotic mesenchyme and otic epithelium in otic development can be dissected. Copyright 2009 Wiley-Liss, Inc.

  2. Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons

    PubMed Central

    Potter, Gregory B.; Petryniak, Magdalena A.; Shevchenko, Eugenia; McKinsey, Gabriel L.; Ekker, Marc; Rubenstein, John L.R.

    2009-01-01

    DLX1 and DLX2 transcription factors are necessary for forebrain GABAergic neuron differentiation, migration, and survival. We generated transgenic mice that express Cre-recombinase under the control of two ultra-conserved DNA elements near the Dlx1&2 locus termed I12b and URE2. We show that Cre-recombinase is active in a “Dlx-pattern” in the embryonic forebrain of transgenic mice. I12b-Cre is more active than URE2-Cre in the medial ganglionic eminences and its derivatives. Fate-mapping of EGFP+ cells in adult Cre;Z/EG animals demonstrated that GABAergic neurons, but not glia, are labeled. Most NPY+, nNOS+, parvalbumin+, and somatostatin+ cells are marked by I12b-Cre in the cortex and hippocampus, while 25-40% of these interneuron subtypes are labeled by URE2-Cre. Labeling of neurons generated between E12.5 to E15.5 indicated differences in birth-dates of EGFP+ cells that populate the olfactory bulb, hippocampus, and cortex. Finally, we provide the first in vivo evidence that both I12b and URE2 are direct targets of DLX2 and require Dlx1 and Dlx2 expression for proper activity. PMID:19026749

  3. Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

    PubMed

    Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

    2017-11-04

    The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin + CD31 - cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin + CD31 - cells. Tnfsf11 fl/Δ Col6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.

    PubMed

    McConville, Thomas Howe; Sullivan, Sean Berger; Gomez-Simmonds, Angela; Whittier, Susan; Uhlemann, Anne-Catrin

    2017-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU). We carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome). Among 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056). Our study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE

  5. Cre/lox-based multiple markerless gene disruption in the genome of the extreme thermophile Thermus thermophilus.

    PubMed

    Togawa, Yoichiro; Nunoshiba, Tatsuo; Hiratsu, Keiichiro

    2018-02-01

    Markerless gene-disruption technology is particularly useful for effective genetic analyses of Thermus thermophilus (T. thermophilus), which have a limited number of selectable markers. In an attempt to develop a novel system for the markerless disruption of genes in T. thermophilus, we applied a Cre/lox system to construct a triple gene disruptant. To achieve this, we constructed two genetic tools, a loxP-htk-loxP cassette and cre-expressing plasmid, pSH-Cre, for gene disruption and removal of the selectable marker by Cre-mediated recombination. We found that the Cre/lox system was compatible with the proliferation of the T. thermophilus HB27 strain at the lowest growth temperature (50 °C), and thus succeeded in establishing a triple gene disruptant, the (∆TTC1454::loxP, ∆TTC1535KpnI::loxP, ∆TTC1576::loxP) strain, without leaving behind a selectable marker. During the process of the sequential disruption of multiple genes, we observed the undesired deletion and inversion of the chromosomal region between multiple loxP sites that were induced by Cre-mediated recombination. Therefore, we examined the effects of a lox66-htk-lox71 cassette by exploiting the mutant lox sites, lox66 and lox71, instead of native loxP sites. We successfully constructed a (∆TTC1535::lox72, ∆TTC1537::lox72) double gene disruptant without inducing the undesired deletion of the 0.7-kbp region between the two directly oriented lox72 sites created by the Cre-mediated recombination of the lox66-htk-lox71 cassette. This is the first demonstration of a Cre/lox system being applicable to extreme thermophiles in a genetic manipulation. Our results indicate that this system is a powerful tool for multiple markerless gene disruption in T. thermophilus.

  6. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase

    PubMed Central

    Hull, Travis D.; Bolisetty, Subashini; DeAlmeida, Angela; Litovsky, Silvio H.; Prabhu, Sumanth D.; Agarwal, Anupam; George, James F.

    2013-01-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (MHC-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice) with mice containing an hHO-1 transgene preceded by a floxed stop signal (CBA-flox mice). MHC-HO-1 overexpress the HO-1 gene and enzymatically protein following TAM administration (40 mg/kg body weight on two consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity and also because inflammation is an important pathological component of many human cardiovascular diseases. PMID:23732814

  7. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

    PubMed

    Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

    2013-08-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

  8. A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination.

    PubMed

    Hartwich, Heiner; Satheesh, Somisetty V; Nothwang, Hans Gerd

    2012-06-14

    Targeted genetic modification in the mouse becomes increasingly important in biomedical and basic science. This goal is most often achieved by use of the Cre/loxP system and numerous Cre-driver mouse lines are currently generated. Their initial characterization requires reporter mouse lines to study the in vivo spatiotemporal activity of Cre. Here, we report a dual fluorescence reporter mouse line, which switches expression from the red fluorescent protein mCherry to eGFP after Cre-mediated recombination. Both fluorescent proteins are expressed from the ubiquitously active and strong CAGGS promoter. Among the founders, we noticed a pink mouse line, expressing high levels of the red fluorescent protein mCherry throughout the entire body. Presence of mCherry in the living animal as well as in almost all organs was clearly visible without optical equipment. Upon Cre-activity, mCherry expression was switched to eGFP, demonstrating functionality of this reporter mouse line. The pink mouse presented here is an attractive novel reporter line for fluorescence-based monitoring of Cre-activity. The high expression of mCherry, which is visible to the naked eye, facilitates breeding and crossing, as no genotyping is required to identify mice carrying the reporter allele. The presence of two fluorescent proteins allows in vivo monitoring of recombined and non-recombined cells. Finally, the pink mouse is an eye-catching animal model to demonstrate the power of transgenic techniques in teaching courses.

  9. CRE-Mediated Transcription and COX-2 Expression in the Pilocarpine Model of Status Epilepticus

    PubMed Central

    Lee, Boyoung; Dziema, Heather; Lee, Kyu Hyun; Choi, Yun-Sik; Obrietan, Karl

    2007-01-01

    Status epilepticus (SE) triggers neuronal death, reactive gliosis and remodeling of synaptic circuitry, thus leading to profound pathological alterations in CNS physiology. These processes are, in part, regulated by the rapid upregulation of both cytotoxic and cytoprotective genes. One pathway that may couple SE to transcriptionally-dependent alterations in CNS physiology is the CREB (cAMP response element-binding protein)/CRE (cAMP response element) cascade. Here, we utilized the pilocarpine model of SE on a mouse strain transgenic for a CRE-reporter construct (β-galactosidase) to begin to characterize how seizure activity regulates the activation state of the CREB/CRE pathway in both glia and neurons of the hippocampus. SE triggered a rapid (4–8 hrs post SE) but transient increase in CRE-mediated gene expression in the neuronal sublayers. In contrast to neurons, SE induced a lasting increase (up to 20 days) in CRE-mediated transcription in both reactive astrocytes and microglia. CRE-mediated gene expression correlated with expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2). To examine the role of CREB in SE-induced COX-2 expression, we generated a transgenic mouse strain that expresses A-CREB, a potent repressor of CREB-dependent transcription. In these animals, the capacity of SE to stimulate COX-2 expression was markedly attenuated, indicating that CREB is a key intermediate in SE-induced COX-2 expression. Collectively these data show that SE triggers two waves of CREB-mediated gene expression, a transient wave in neurons and a long-lasting wave in reactive glial cells, and that CREB couples SE to COX-2 expression. PMID:17029965

  10. Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

    PubMed

    Ramirez-GarciaLuna, Jose Luis; Chan, Daniel; Samberg, Robert; Abou-Rjeili, Mira; Wong, Timothy H; Li, Ailian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Henderson, Janet E; Martineau, Paul A

    2017-01-01

    In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

  11. Defective bone repair in mast cell-deficient Cpa3Cre/+ mice

    PubMed Central

    Chan, Daniel; Samberg, Robert; Abou-Rjeili, Mira; Wong, Timothy H.; Li, Ailian; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Henderson, Janet E.; Martineau, Paul A.

    2017-01-01

    In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT) and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1) mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2) re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3) the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair. PMID:28350850

  12. The FEM simulation of continuous rotary extrusion (CRE) of aluminum alloy AA3003

    NASA Astrophysics Data System (ADS)

    Rajendran, Nijenthan; Valberg, Henry; Misiolek, Wojciech Z.

    2017-10-01

    Continuous Rotary Extrusion (CRE) process is also known in literature under Conform TM name and it is mainly used for the continuous extrusion of Aluminum and Copper alloys. CRE use a feedstock in the form of rod, powders and chips, which are fed into the groove of the rotating wheel. As the wheel rotates the feedstock moves along with it due to friction with the wheel. Once the feedstock reaches the abutment the material deforms plastically and it is extruded through the die. CRE has lot to offer when compared to other more conventional extrusion processes such as low energy input, no limit in billet length as it is a continuous process as well as improved material physical properties due to plastic deformation under constant parameters. In this work a FEM model has been developed using Deform TM 3D, to study the metal flow and state variables of AA3003 CRE extrusion. The effect of extrusion wheel velocity has been investigated. The results show that increase in wheel velocity will heat up the feedstock metal due to high shear deformation and higher friction, which significantly changes metal flow conditions at the die exit.

  13. Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination.

    PubMed

    Betz, U A; Vosshenrich, C A; Rajewsky, K; Müller, W

    1996-10-01

    The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments. We generated nestin-cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the gamma-chain of the interleukin-2 receptor (IL-2R gamma); in these animals, the IL-2R gamma-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase beta die perinatally, we studied the effects of DNA polymerase beta deficiency in mosaic animals. We found that some of the mosaic polymerase beta-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase beta-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage. The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase beta, deficient cells are already

  14. Restoring pollen fertility in transgenic male-sterile eggplant by Cre/loxp-mediated site-specific recombination system.

    PubMed

    Cao, Bihao; Huang, Zhiyin; Chen, Guoju; Lei, Jianjun

    2010-04-01

    This study was designed to control plant fertility by cell lethal gene Barnase expressing at specific developmental stage and in specific tissue of male organ under the control of Cre/loxP system, for heterosis breeding, producing hybrid seed of eggplant. The Barnase-coding region was flanked by loxP recognition sites for Cre-recombinase. The eggplant inbred/pure line ('E-38') was transformed with Cre gene and the inbred/pure line ('E-8') was transformed with the Barnase gene situated between loxp. The experiments were done separately, by means of Agrobacterium co-culture. Four T(0) -plants with the Barnase gene were obtained, all proved to be male-sterile and incapable of producing viable pollen. Flowers stamens were shorter, but the vegetative phenotype was similar to wild-type. Five T (0) -plants with the Cre gene developed well, blossomed out and set fruit normally. The crossing of male-sterile Barnase-plants with Cre expression transgenic eggplants resulted in site-specific excision with the male-sterile plants producing normal fruits. With the Barnase was excised, pollen fertility was fully restored in the hybrids. The phenotype of these restored plants was the same as that of the wild-type. Thus, the Barnase and Cre genes were capable of stable inheritance and expression in progenies of transgenic plants.

  15. Site-specific DNA excision in transgenic rice with a cell-permeable cre recombinase.

    PubMed

    Cao, Ming-Xia; Huang, Jian-Qiu; Yao, Quan-Hong; Liu, Sheng-Jun; Wang, Cheng-Long; Wei, Zhi-Ming

    2006-01-01

    The removal of selected marker genes from transgenic plants is necessary to address biosafety concerns and to carry out further experiments with transgenic organisms. In the present study, the 12-amino-acid membrane translocation sequence (MTS) from the Kaposi fibroblast growth factor (FGF)-4 was used as a carrier to deliver enzymatically active Cre proteins into living plant cells, and to produce a site-specific DNA excision in transgenic rice plants. The process, which made cells permeable to Cre recombinase-mediated DNA recombination, circumvented the need to express Cre under spatiotemporal control and was proved to be a simple and efficient system to achieve marker-free transgenic plants. The ultimate aim of the present study is to develop commercial rice cultivars free from selected marker genes to hasten public acceptance of transgenic crops.

  16. Strategic Plan for Higher Education, 2008-2017. Executive Summary

    ERIC Educational Resources Information Center

    Fingerhut, Eric D.

    2008-01-01

    If the State of Ohio is to grow and prosper, it must raise the education level of its population. The goal of this 10-year strategic plan is to raise the educational attainment of the state each year, and to close the gap between Ohio and competitor states and nations. To accomplish this goal stakeholders must do three things: (1) Graduate more…

  17. Induced Pluripotent Stem Cells Generated from P0-Cre;Z/EG Transgenic Mice

    PubMed Central

    Ogawa, Yasuhiro; Eto, Akira; Miyake, Chisato; Tsuchida, Nana; Miyake, Haruka; Takaku, Yasuhiro; Hagiwara, Hiroaki; Oishi, Kazuhiko

    2015-01-01

    Neural crest (NC) cells are a migratory, multipotent cell population that arises at the neural plate border, and migrate from the dorsal neural tube to their target tissues, where they differentiate into various cell types. Abnormal development of NC cells can result in severe congenital birth defects. Because only a limited number of cells can be obtained from an embryo, mechanistic studies are difficult to perform with directly isolated NC cells. Protein zero (P0) is expressed by migrating NC cells during the early embryonic period. In the P0-Cre;Z/EG transgenic mouse, transient activation of the P0 promoter induces Cre-mediated recombination, indelibly tagging NC-derived cells with enhanced green fluorescent protein (EGFP). Induced pluripotent stem cell (iPSC) technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here, we report the generation of iPSCs from the P0-Cre;Z/EG mouse. P0-Cre;Z/EG mouse-derived iPSCs (P/G-iPSCs) exhibited pluripotent stem cell properties. In lineage-directed differentiation studies, P/G-iPSCs were efficiently differentiated along the neural lineage while expressing EGFP. These results suggest that P/G-iPSCs are useful to study NC development and NC-associated diseases. PMID:26382630

  18. Induced Pluripotent Stem Cells Generated from P0-Cre;Z/EG Transgenic Mice.

    PubMed

    Ogawa, Yasuhiro; Eto, Akira; Miyake, Chisato; Tsuchida, Nana; Miyake, Haruka; Takaku, Yasuhiro; Hagiwara, Hiroaki; Oishi, Kazuhiko

    2015-01-01

    Neural crest (NC) cells are a migratory, multipotent cell population that arises at the neural plate border, and migrate from the dorsal neural tube to their target tissues, where they differentiate into various cell types. Abnormal development of NC cells can result in severe congenital birth defects. Because only a limited number of cells can be obtained from an embryo, mechanistic studies are difficult to perform with directly isolated NC cells. Protein zero (P0) is expressed by migrating NC cells during the early embryonic period. In the P0-Cre;Z/EG transgenic mouse, transient activation of the P0 promoter induces Cre-mediated recombination, indelibly tagging NC-derived cells with enhanced green fluorescent protein (EGFP). Induced pluripotent stem cell (iPSC) technology offers new opportunities for both mechanistic studies and development of stem cell-based therapies. Here, we report the generation of iPSCs from the P0-Cre;Z/EG mouse. P0-Cre;Z/EG mouse-derived iPSCs (P/G-iPSCs) exhibited pluripotent stem cell properties. In lineage-directed differentiation studies, P/G-iPSCs were efficiently differentiated along the neural lineage while expressing EGFP. These results suggest that P/G-iPSCs are useful to study NC development and NC-associated diseases.

  19. R/L, a double reporter mouse line that expresses luciferase gene upon Cre-mediated excision, followed by inactivation of mRFP expression.

    PubMed

    Jia, Junshuang; Lin, Xiaolin; Lin, Xia; Lin, Taoyan; Chen, Bangzhu; Hao, Weichao; Cheng, Yushuang; Liu, Yu; Dian, Meijuan; Yao, Kaitai; Xiao, Dong; Gu, Weiwang

    2016-10-01

    The Cre/loxP system has become an important tool for the conditional gene knockout and conditional gene expression in genetically engineered mice. The applications of this system depend on transgenic reporter mouse lines that provide Cre recombinase activity with a defined cell type-, tissue-, or developmental stage-specificity. To develop a sensitive assay for monitoring Cre-mediated DNA excisions in mice, we generated Cre-mediated excision reporter mice, designated R/L mice (R/L: mRFP(monomeric red fluorescent protein)/luciferase), express mRFP throughout embryonic development and adult stages, while Cre-mediated excision deletes a loxP-flanked mRFP reporter gene and STOP sequence, thereby activating the expression of the second reporter gene luciferase, as assayed by in vivo and ex vivo bioluminescence imaging. After germ line deletion of the floxed mRFP and STOP sequence in R/L mice by EIIa-Cre mice, the resulting luciferase transgenic mice in which the loxP-mRFP-STOP-loxP cassette is excised from all cells express luciferase in all tissues and organs examined. The expression of luciferase transgene was activated in liver of RL/Alb-Cre double transgenic mice and in brain of RL/Nestin-Cre double transgenic mice when R/L reporter mice were mated with Alb-Cre mice and Nestin-Cre mice, respectively. Our findings reveal that the double reporter R/L mouse line is able to indicate the occurrence of Cre-mediated excision from early embryonic to adult lineages. Taken together, these findings demonstrate that the R/L mice serve as a sensitive reporter for Cre-mediated DNA excision both in living animals and in organs, tissues, and cells following necropsy.

  20. STIM1fl/fl Ksp-Cre Mouse has Impaired Renal Water Balance

    PubMed Central

    Cebotaru, Liudmila; Cebotaru, Valeriu; Wang, Hua; Arend, Lois J.; Guggino, William B.

    2016-01-01

    Background/AIM STIM1 is as an essential component in store operated Ca2+entry. However give the paucity of information on the role of STIM1 in kidney, the aim was to study the function of STIM1 in the medulla of the kidney. Methods we crossed a Ksp-cre mouse with another mouse containing two loxP sites flanking Exon 6 of STIM1. The Ksp-cre mouse is based upon the Ksp-cadherin gene promoter which expresses cre recombinase in developing nephrons, collecting ducts (SD) and thick ascending limbs (TAL) of the loop of Henle. Results The offspring of these mice are viable without gross morphological changes, however, we noticed that the STIM1 Ksp-cre knockout mice produced more urine compared to control. To examine this more carefully, we fed mice low (LP) and high protein (HP) diets respectively. When mice were fed HP diet STIM1 ko mice had significantly increased urinary volume and lower specific gravity compared to wt mice. In STIM1 ko mice fed HP diet urine creatinine and urea were significantly lower compared to wt mice fed HP diet, however the fractional excretion was the same. Conclusion These data support the idea that STIM1 ko mice have impaired urinary concentrating ability when challenged with HP diet is most likely caused by impaired Ca2+-dependent signal transduction through the vasopressin receptor cascade. PMID:27336410

  1. Gfi1-Cre knock-in mouse line: A tool for inner ear hair cell-specific gene deletion

    PubMed Central

    Yang, Hua; Gan, Jean; Xie, Xiaoling; Deng, Min; Feng, Liang; Chen, Xiaowei; Gao, Zhiqiang; Gan, Lin

    2010-01-01

    Summary Gfi1encodes a zinc-finger transcription factor essential for the development and maintenance of haematopoiesis and the inner ear. In mouse inner ear, Gfi1 expression is confined to hair cells during development and in adulthood. To construct a genetic tool for inner ear hair cell-specific gene deletion, we generated a Gfi1-Cre mouse line by knocking-in Cre coding sequences into the Gfi1 locus and inactivating the endogenous Gfi1. The specificity and efficiency of Gfi1-Cre recombinase-mediated recombination in the developing inner ear was revealed through the expression of the conditional R26R-lacZ reporter gene. The onset of lacZ expression in the Gfi1Cre/+ inner ear was first detected at E13.5 in the vestibule and at E15.5 in the cochlea, coinciding with the generation of hair cells. Throughout inner ear development, lacZ expression was detected only in hair cells. Thus, Gfi1-Cre knock-in mouse line provides a useful tool for gene manipulations specifically in inner ear hair cells. PMID:20533399

  2. Development of selectable marker free, insect resistant, transgenic mustard (Brassica juncea) plants using Cre/lox mediated recombination

    PubMed Central

    2013-01-01

    Background Antibiotic/ herbicide resistant marker genes have been proven to be very useful in plant transformation for the initial selection of desired transgenic events. However, presence of these genes in the genetically modified crops may render the crop less acceptable to the consumers. Among several different approaches, the effectiveness of Cre/lox mediated recombination strategy for selectable marker gene (SMG) elimination has previously been demonstrated by different groups in several plants including Brassica. In the present study exploiting Cre/lox mediated recombination strategy, attempt has been made for selectable marker gene elimination from Allium sativum leaf agglutinin (ASAL) expressing Brassica plants with hemipteran insect resistant phenotype. Results Allium sativum leaf agglutinin (ASAL) linked with lox flanked hygromycin resistant (hpt) gene was introduced in mustard. Cre recombinase gene cassette was also integrated in separate event. A Cre/lox mediated recombination using crossing strategy was adopted to remove the hpt gene from the subsequent generation of selected hybrid events. Reciprocal crosses were made between T1ASAL-lox-hpt-lox and cre-bar plants. Marker gene elimination was confirmed in the resulting F1 hybrid progenies by PCR analysis, using hpt, cre and ASAL specific primers followed by Southern hybridization. In marker free plants, expression of ASAL was also confirmed by western blotting and ELISA analysis. Retention of functionality of expressed ASAL was investigated by agglutination assay using rabbit erythrocytes. Expressed ASAL was also found to be thermo-sensitive. In planta insect bioassay on F1 hybrid progenies exhibited detrimental effect on the performance of devastating target pest, Lipaphis erysimi. The F1 hybrid hpt negative, ASAL positive plants were allowed to self- fertilize to obtain F2 progeny plants. In some of these plants cre gene was found to be segregated out of the ASAL gene by genetic segregation yielding

  3. Generation of Oxtr cDNA(HA)-Ires-Cre Mice for Gene Expression in an Oxytocin Receptor Specific Manner.

    PubMed

    Hidema, Shizu; Fukuda, Tomokazu; Hiraoka, Yuichi; Mizukami, Hiroaki; Hayashi, Ryotaro; Otsuka, Ayano; Suzuki, Shingo; Miyazaki, Shinji; Nishimori, Katsuhiko

    2016-05-01

    The neurohypophysial hormone oxytocin (OXT) and its receptor (OXTR) have critical roles in the regulation of pro-social behaviors, including social recognition, pair bonding, parental behavior, and stress-related responses. Supporting this hypothesis, a portion of patients suffering from autism spectrum disorder have mutations, such as single nucleotide polymorphisms, or epigenetic modifications in their OXTR gene. We previously reported that OXTR-deficient mice exhibit pervasive social deficits, indicating the critical role of OXTR in social behaviors. In the present study, we generated Oxtr cDNA(HA)-Ires-Cre knock-in mice, expressing both OXTR and Cre recombinase under the control of the endogenous Oxtr promoter. Knock-in cassette of Oxtr cDNA(HA)-Ires-Cre consisted of Oxtr cDNA tagged with the hemagglutinin epitope at the 3' end (Oxtr cDNA(HA)), internal ribosomal entry site (Ires), and Cre. Cre was expressed in the uterus, mammary gland, kidney, and brain of Oxtr cDNA(HA)-Ires-Cre knock-in mice. Furthermore, the distribution of Cre in the brain was similar to that observed in Oxtr-Venus fluorescent protein expressing mice (Oxtr-Venus), another animal model previously generated by our group. Social behavior of Oxtr cDNA(HA)-Ires-Cre knock-in mice was similar to that of wild-type animals. We demonstrated that this construct is expressed in OXTR-expressing neurons specifically after an infection with the recombinant adeno-associated virus carrying the flip-excision switch vector. Using this system, we showed the transport of the wheat-germ agglutinin tracing molecule from the OXTR-expressing neurons to the innervated neurons in knock-in mice. This study might contribute to the monosynaptic analysis of neuronal circuits and to the optogenetic analysis of neurons expressing OXTR. © 2015 Wiley Periodicals, Inc.

  4. System's flips in climate-related energy (CRE) systems

    NASA Astrophysics Data System (ADS)

    Ramos, Maria-Helena; Creutin, Jean-Dominique; Engeland, Kolbjørn; François, Baptiste; Renard, Benjamin

    2014-05-01

    Several modern environmental questions invite to explore the complex relationships between natural phenomena and human behaviour at a range of space and time scales. This usually involves a number of cause-effect (causal) relationships, linking actions and events. In lay terms, 'effect' can be defined as 'what happened' and 'cause', 'why something happened.' In a changing world or merely moving from one scale to another, shifts in perspective are expected, bringing some phenomena into the foreground and putting others to the background. Systems can thus flip from one set of causal structures to another in response to environmental perturbations and human innovations or behaviors, for instance, as space-time signatures are modified. The identification of these flips helps in better understanding and predicting how societies and stakeholders react to a shift in perspective. In this study, our motivation is to investigate possible consequences of the shift to a low carbon economy in terms of socio-technico systems' flips. The focus is on the regional production of Climate-Related Energy (CRE) (hydro-, wind- and solar-power). We search for information on historic shifts that may help defining the forcing conditions of abrupt changes and extreme situations. We identify and present a series of examples in which we try to distinguish the various tipping points, thresholds, breakpoints and regime shifts that are characteristic of complex systems in the CRE production domain. We expect that with these examples our comprehension of the question will be enriched, providing us the elements needed to better validate modeling attempts, to predict and manage flips of complex CRE production systems. The work presented is part of the FP7 project COMPLEX (Knowledge based climate mitigation systems for a low carbon economy; http://www.complex.ac.uk/).

  5. Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification

    PubMed Central

    Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida

    2017-01-01

    Abstract Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. PMID:28053125

  6. Agrobacterium-mediated transformation of maize (Zea mays) with Cre-lox site specific recombination cassettes in BIBAC vectors.

    PubMed

    Vega, Juan M; Yu, Weichang; Han, Fangpu; Kato, Akio; Peters, Eric M; Zhang, Zhanyuan J; Birchler, James A

    2008-04-01

    The Cre/loxP site-specific recombination system has been applied in various plant species including maize (Zea mays) for marker gene removal, gene targeting, and functional genomics. A BIBAC vector system was adapted for maize transformation with a large fragment of genetic material including a herbicide resistance marker gene, a 30 kb yeast genomic fragment as a marker for fluorescence in situ hybridization (FISH), and a 35S-lox-cre recombination cassette. Seventy-five transgenic lines were generated from Agrobacterium-mediated transformation of a maize Hi II line with multiple B chromosomes. Eighty-four inserts have been localized among all 10 A chromosome pairs by FISH using the yeast DNA probe together with a karyotyping cocktail. No inserts were found on the B chromosomes; thus a bias against the B chromosomes by the Agrobacterium-mediated transformation was revealed. The expression of a cre gene was confirmed in 68 of the 75 transgenic lines by a reporter construct for cre/lox mediated recombination. The placement of the cre/lox site-specific recombination system in many locations in the maize genome will be valuable materials for gene targeting and chromosome engineering.

  7. Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes.

    PubMed

    Koehler, Sybille; Brähler, Sebastian; Braun, Fabian; Hagmann, Henning; Rinschen, Markus M; Späth, Martin R; Höhne, Martin; Wunderlich, F Thomas; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

    2017-06-01

    Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides. Independent expression of endogenous podocin, codon improved Cre, and mTomato was confirmed by immunofluorescence, fluorescent activated cell sorting and protein analyses. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice developed normally and did not show any signs of glomerular disease or off-target effects under basal conditions and in states of disease. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type -mediated gene recombination was superior to conventional hNphs2.Cre mice-mediated gene recombination. Last, we compared Cre efficiency in a disease model by mating Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type and hNphs2.Cre mice to Phb2 fl/fl mice. The podocyte-specific Phb2 knockout by Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice resulted in an aggravated glomerular injury as compared to a podocyte-specific Phb2 gene deletion triggered by hNphs2.Cre. Thus, we generated the first tricistronic podocyte mouse model combining enhanced Cre recombinase efficiency and fluorescent labeling in podocytes without the need for additional matings with conventional reporter mouse lines. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  8. Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification.

    PubMed

    Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida; Cox, J Colin; Warming, Søren

    2017-05-05

    Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Nonlocal symmetry and explicit solutions from the CRE method of the Boussinesq equation

    NASA Astrophysics Data System (ADS)

    Zhao, Zhonglong; Han, Bo

    2018-04-01

    In this paper, we analyze the integrability of the Boussinesq equation by using the truncated Painlevé expansion and the CRE method. Based on the truncated Painlevé expansion, the nonlocal symmetry and Bäcklund transformation of this equation are obtained. A prolonged system is introduced to localize the nonlocal symmetry to the local Lie point symmetry. It is proved that the Boussinesq equation is CRE solvable. The two-solitary-wave fusion solutions, single soliton solutions and soliton-cnoidal wave solutions are presented by means of the Bäcklund transformations.

  10. Fabp4-CreER lineage tracing reveals two distinctive coronary vascular populations.

    PubMed

    He, Lingjuan; Tian, Xueying; Zhang, Hui; Wythe, Joshua D; Zhou, Bin

    2014-11-01

    Over the last two decades, genetic lineage tracing has allowed for the elucidation of the cellular origins and fates during both embryogenesis and in pathological settings in adults. Recent lineage tracing studies using Apln-CreER tool indicated that a large number of post-natal coronary vessels do not form from pre-existing vessels. Instead, they form de novo after birth, which represents a coronary vascular population (CVP) distinct from the pre-existing one. Herein, we present new coronary vasculature lineage tracing results using a novel tool, Fabp4-CreER. Our results confirm the distinct existence of two unique CVPs. The 1(st) CVP, which is labelled by Fabp4-CreER, arises through angiogenic sprouting of pre-existing vessels established during early embryogenesis. The 2(nd) CVP is not labelled by Fabp4, suggesting that these vessels form de novo, rather than through expansion of the 1(st) CVP. These results support the de novo formation of vessels in the post-natal heart, which has implications for studies in cardiovascular disease and heart regeneration. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

    PubMed

    Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

    2015-12-01

    For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

  12. Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

    PubMed

    Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

    2016-10-18

    Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

  13. Mice expressing GFP and CreER in osteochondro progenitor cells in the periosteum.

    PubMed

    Kawanami, Aya; Matsushita, Takehiko; Chan, Yuk Yu; Murakami, Shunichi

    2009-08-28

    We generated Prx1CreER-GFP transgenic mice that express tamoxifen-inducible Cre recombinase and GFP under the control of a 2.4 kb Prx1 promoter. The transgene is expressed in osteochondro progenitor cells in the developing limb buds and in a subpopulation of periosteal cells that is closely associated with the cortical bone. GFP-expressing cells isolated from the diaphyses of long bones by cell sorting express multiple markers of periosteal cells, including Prx1, Fgf18, Tenascin-W, Periostin, and Thrombospondin 2. In addition, these cells undergo chondrogenic and osteogenic differentiation in culture upon induction. Cell fate analysis using the Rosa26 LacZ reporter indicated that transgene-expressing cells give rise to some of the chondrocytes and osteoblasts in the fracture callus. Collectively, these observations strongly suggest that the transgene-expressing cells are osteochondro progenitor cells in the periosteum. The established Prx1CreER-GFP mice would offer novel approaches for analyzing the functions of periosteal cells in vitro and in vivo.

  14. Transient Cnp expression by early progenitors causes Cre-Lox-based reporter lines to map profoundly different fates.

    PubMed

    Tognatta, Reshmi; Sun, Wenjing; Goebbels, Sandra; Nave, Klaus-Armin; Nishiyama, Akiko; Schoch, Susanne; Dimou, Leda; Dietrich, Dirk

    2017-02-01

    NG2 expressing oligodendroglial precursor cells are ubiquitous in the central nervous system and the only cell type cycling throughout life. Previous fate mapping studies have remained inconsistent regarding the question whether NG2 cells are capable of generating certain types of neurons. Here, we use CNP-Cre mice to map the fate of a sub-population of NG2 cells assumed to be close to differentiation. When crossing these mice with the ROSA26/YFP Cre-reporter line we discovered large numbers of reporter-expressing pyramidal neurons in the piriform and dorsal cortex. In contrast, when using Z/EG reporter mice to track the fate of Cnp-expressing NG2 cells only oligodendroglial cells were found reporter positive. Using BrdU-based birth dating protocols and inducible NG2CreER:ROSA26/YFP mice we show that YFP positive neurons are generated from radial glial cells and that these radial glial cells display temporary and low level activity of certain oligodendroglial genes sufficient to recombine the Cre-inducible reporter gene in ROSA26/YFP but not in Z/EG mice. Taken together, we did not obtain evidence for generation of neurons from NG2 cells. Our results suggest that with an appropriate reporter system Cnp activity can be used to define a proliferative subpopulation of NG2 cells committed to generate oligodendrocytes. However, the strikingly different results obtained from ROSA26/YFP versus Z/EG mice demonstrate that the choice of Cre-reporter line can be of crucial importance for fate mapping studies and other applications of the Cre-lox technology. GLIA 2017;65:342-359. © 2016 Wiley Periodicals, Inc.

  15. Quantitative interdependence of coeffectors, CcpA and cre in carbon catabolite regulation of Bacillus subtilis.

    PubMed

    Seidel, Gerald; Diel, Marco; Fuchsbauer, Norbert; Hillen, Wolfgang

    2005-05-01

    The phosphoproteins HPrSerP and CrhP are the main effectors for CcpA-mediated carbon catabolite regulation (CCR) in Bacillus subtilis. Complexes of CcpA with HPrSerP or CrhP regulate genes by binding to the catabolite responsive elements (cre). We present a quantitative analysis of HPrSerP and CrhP interaction with CcpA by surface plasmon resonance (SPR) revealing small and similar equilibrium constants of 4.8 +/- 0.4 microm for HPrSerP-CcpA and 19.1 +/- 2.5 microm for CrhP-CcpA complex dissociation. Forty millimolar fructose-1,6-bisphosphate (FBP) or glucose-6-phosphate (Glc6-P) increases the affinity of HPrSerP to CcpA at least twofold, but have no effect on CrhP-CcpA binding. Saturation of binding of CcpA to cre as studied by fluorescence and SPR is dependent on 50 microm of HPrSerP or > 200 microm CrhP. The rate constants of HPrSerP-CcpA-cre complex formation are k(a) = 3 +/- 1 x 10(6) m(-1).s(-1) and k(d) = 2.0 +/- 0.4 x 10(-3).s(-1), resulting in a K(D) of 0.6 +/- 0.3 nm. FBP and Glc6-P stimulate CcpA-HPrSerP but not CcpA-CrhP binding to cre. Maximal HPrSerP-CcpA-cre complex formation in the presence of 10 mm FBP requires about 10-fold less HPrSerP. These data suggest a specific role for FBP and Glc6-P in enhancing only HPrSerP-mediated CCR.

  16. Flavonoids and Auxin Transport Inhibitors Rescue Symbiotic Nodulation in the Medicago truncatula Cytokinin Perception Mutant cre1

    PubMed Central

    Ng, Jason Liang Pin; Hassan, Samira; Truong, Thy T.; Hocart, Charles H.; Laffont, Carole; Frugier, Florian; Mathesius, Ulrike

    2015-01-01

    Initiation of symbiotic nodules in legumes requires cytokinin signaling, but its mechanism of action is largely unknown. Here, we tested whether the failure to initiate nodules in the Medicago truncatula cytokinin perception mutant cre1 (cytokinin response1) is due to its altered ability to regulate auxin transport, auxin accumulation, and induction of flavonoids. We found that in the cre1 mutant, symbiotic rhizobia cannot locally alter acro- and basipetal auxin transport during nodule initiation and that these mutants show reduced auxin (indole-3-acetic acid) accumulation and auxin responses compared with the wild type. Quantification of flavonoids, which can act as endogenous auxin transport inhibitors, showed a deficiency in the induction of free naringenin, isoliquiritigenin, quercetin, and hesperetin in cre1 roots compared with wild-type roots 24 h after inoculation with rhizobia. Coinoculation of roots with rhizobia and the flavonoids naringenin, isoliquiritigenin, and kaempferol, or with the synthetic auxin transport inhibitor 2,3,5,-triiodobenzoic acid, rescued nodulation efficiency in cre1 mutants and allowed auxin transport control in response to rhizobia. Our results suggest that CRE1-dependent cytokinin signaling leads to nodule initiation through the regulation of flavonoid accumulation required for local alteration of polar auxin transport and subsequent auxin accumulation in cortical cells during the early stages of nodulation. PMID:26253705

  17. Extraction of nobiletin from Citrus Unshiu peels by supercritical fluid and its CRE-mediated transcriptional activity.

    PubMed

    Oba, Chisato; Ota, Masaki; Nomura, Koichiro; Fujiwara, Hironori; Takito, Jiro; Sato, Yoshiyuki; Ohizumi, Yasushi; Inomata, Hiroshi

    2017-04-15

    Polymethoxyflavone (PMF) is one of bioactive compounds in Citrus Unshiu and included mainly in the peels rather than the fruits, seeds and leaves. Supercritical CO 2 extraction is one candidate for selective extraction of polymethoxyflavone and in this study, supercritical CO 2 extraction with/without ethanol entrainer from Citrus Unshiu peels was examined at a temperature of 333K and a pressure of 30MPa. CRE (cyclic AMP response element)-mediated transcriptional assay was examined by using the extracts from supercritical fluid extraction. The results showed that extracts including nobiletin increased with increasing ethanol concentration in supercritical CO 2 and the elapsed extraction time. Extracts at ethanol concentration of 5 mol% showed high CRE-mediated transcription activity. This can be caused by activity of the extract including nobiletin in addition to the other methoxylated flavonoid species such as tangeretin. Extracts at ethanol concentration of 50% showed the highest CRE-mediated transcription activity, which can be attributed to flavonoid glycoside such as hesperidin. From our investigations, flavonoid glycoside can be one of promoters of CRE-mediated transcription activity. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.

    PubMed

    Feyerabend, Thorsten B; Weiser, Anne; Tietz, Annette; Stassen, Michael; Harris, Nicola; Kopf, Manfred; Radermacher, Peter; Möller, Peter; Benoist, Christophe; Mathis, Diane; Fehling, Hans Jörg; Rodewald, Hans-Reimer

    2011-11-23

    Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Unexpected Cartilage Phenotype in CD4-Cre-Conditional SOS-Deficient Mice.

    PubMed

    Guittard, Geoffrey; Gallardo, Devorah L; Li, Wenmei; Melis, Nicolas; Lui, Julian C; Kortum, Robert L; Shakarishvili, Nicholas G; Huh, Sunmee; Baron, Jeffrey; Weigert, Roberto; Kramer, Joshua A; Samelson, Lawrence E; Sommers, Connie L

    2017-01-01

    RAS signaling is central to many cellular processes and SOS proteins promote RAS activation. To investigate the role of SOS proteins in T cell biology, we crossed Sos1 f/f Sos2 -/- mice to CD4-Cre transgenic mice. We previously reported an effect of these mutations on T cell signaling and T cell migration. Unexpectedly, we observed nodules on the joints of greater than 90% of these mutant mice at 5 months of age, especially on the carpal joints. As the mice aged further, some also displayed joint stiffness, hind limb paralysis, and lameness. Histological analysis indicated that the abnormal growth in joints originated from dysplastic chondrocytes. Second harmonic generation imaging of the carpal nodules revealed that nodules were encased by rich collagen fibrous networks. Nodules formed in mice also deficient in RAG2, indicating that conventional T cells, which undergo rearrangement of the T cell antigen receptor, are not required for this phenotype. CD4-Cre expression in a subset of cells, either immune lineage cells (e.g., non-conventional T cells) or non-immune lineage cells (e.g., chondrocytes) likely mediates the dramatic phenotype observed in this study. Disruptions of genes in the RAS signaling pathway are especially likely to cause this phenotype. These results also serve as a cautionary tale to those intending to use CD4-Cre transgenic mice to specifically delete genes in conventional T cells.

  20. Self-excising Cre/mutant lox marker recycling system for multiple gene integrations and consecutive gene deletions in Aspergillus oryzae.

    PubMed

    Zhang, Silai; Ban, Akihiko; Ebara, Naoki; Mizutani, Osamu; Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2017-04-01

    In this study, we developed a self-excising Cre/loxP-mediated marker recycling system with mutated lox sequences to introduce a number of biosynthetic genes into Aspergillus oryzae. To construct the self-excising marker cassette, both the selectable marker, the Aspergillus nidulans adeA gene, and the Cre recombinase gene (cre), conditionally expressed by the xylanase-encoding gene promoter, were designed to be located between the mutant lox sequences, lox66 and lox71. However, construction of the plasmid failed, possibly owing to a slight expression of cre downstream of the fungal gene promoter in Escherichia coli. Hence, to avoid the excision of the cassette in E. coli, a 71-bp intron of the A. oryzae xynG2 gene was inserted into the cre gene. The A. oryzae adeA deletion mutant was transformed with the resulting plasmid in the presence of glucose, and the transformants were cultured in medium containing xylose as the sole carbon source. PCR analysis of genomic DNA from resultant colonies revealed the excision of both the marker and Cre expression construct, indicating that the self-excising marker cassette was efficient at removing the selectable marker. Using the marker recycling system, hyperproduction of kojic acid could be achieved in A. oryzae by the introduction of two genes that encode oxidoreductase and transporter. Furthermore, we also constructed an alternative marker recycling cassette bearing the A. nidulans pyrithiamine resistant gene (ptrA) as a dominant selectable marker. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Cre-driver lines used for genetic fate mapping of neural crest cells in the mouse: An overview.

    PubMed

    Debbache, Julien; Parfejevs, Vadims; Sommer, Lukas

    2018-04-19

    The neural crest is one of the embryonic structures with the broadest developmental potential in vertebrates. Morphologically, neural crest cells emerge during neurulation in the dorsal folds of the neural tube before undergoing an epithelial-to-mesenchymal transition (EMT), delaminating from the neural tube, and migrating to multiple sites in the growing embryo. Neural crest cells generate cell types as diverse as peripheral neurons and glia, melanocytes, and so-called mesectodermal derivatives that include craniofacial bone and cartilage and smooth muscle cells in cardiovascular structures. In mice, the fate of neural crest cells has been determined mainly by means of transgenesis and genome editing technologies. The most frequently used method relies on the Cre-loxP system, in which expression of Cre-recombinase in neural crest cells or their derivatives genetically enables the expression of a Cre-reporter allele, thus permanently marking neural crest-derived cells. Here, we provide an overview of the Cre-driver lines used in the field and discuss to what extent these lines allow precise neural crest stage and lineage-specific fate mapping. © 2018 The Authors Genesis: The Journal of Genetics and Development Published by Wiley Periodicals, Inc.

  2. Esrrb-Cre Excises loxP-Flanked Alleles in Early Four-Cell Embryos

    PubMed Central

    Kim, Suyeon; Shaffer, Benjamin; Simerly, Calvin R.; Richard Chaillet, J.; Barak, Yaacov

    2015-01-01

    Among transgenic mice with ubiquitous Cre recombinase activity, all strains to date excise loxP-flanked (floxed) alleles, either at or before the zygote stage or at nondescript stages of development. This manuscript describes a new mouse strain, in which Cre recombinase, integrated into the Esrrb locus, efficiently excises floxed alleles in pre-implantation embryos at the onset of the four-cell stage. By enabling inactivation of genes only after the embryo has undergone two cleavages, this strain should facilitate in vivo studies of genes with essential gametic or zygotic functions. In addition, this study describes a new, highly pluripotent hybrid C57BL/6J × 129S1/SvImJ mouse embryonic stem cell line, HYB12, in which this knock-in and additional targeted alleles have been generated. PMID:26663459

  3. Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

    PubMed

    Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

    2016-10-01

    Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine.

    PubMed

    Sun, Ming-Yue; Zhang, Miao; Chen, Shui-Ling; Zhang, Shu-Ping; Guo, Chun-Yu; Wang, Jing-Shang; Liu, Xin; Miao, Yang; Yin, Hui-Jun

    2018-01-01

    Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin

  5. Strategic planning in diagnostic imaging: meeting the challenge.

    PubMed

    Lexa, Frank J

    2008-02-01

    The 21st century has raised new and significant challenges to the practice of diagnostic imaging. Radiologists will have to navigate a difficult path as they face threats from disruptive technologies, adverse demographic changes, pressures to limit reimbursement both from the public and from the private sectors, increased domestic and crossborder competition, and many others. Success in these trying times will require greater attention to strategic planning if we are to thrive and survive in radiology. Strategic planning and tactical implementation methodologies were reviewed, from Sun Tzu to the present day, for applicability to the needs of modern radiology groups. A framework for developing and implementing strategic plans was constructed to assist radiology leaders and groups in considering the spectrum of tasks, from gathering intelligence, to developing scenarios, to implementing and evaluating tactical plans. Strategy and tactics are too important to be ignored or left to others. They need to be core activities for all radiology leaders. Frameworks can be used to help in providing structure and rigour to strategic planning efforts at the department and group level.

  6. Nestin-Cre Mice Are Affected by Hypopituitarism, Which Is Not Due to Significant Activity of the Transgene in the Pituitary Gland

    PubMed Central

    Galichet, Christophe; Lovell-Badge, Robin; Rizzoti, Karine

    2010-01-01

    Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report. PMID:20625432

  7. Strategic planning decision making using fuzzy SWOT-TOPSIS with reliability factor

    NASA Astrophysics Data System (ADS)

    Mohamad, Daud; Afandi, Nur Syamimi; Kamis, Nor Hanimah

    2015-10-01

    Strategic planning is a process of decision making and action for long-term activities in an organization. The Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis has been commonly used to help organizations in strategizing their future direction by analyzing internal and external environment. However, SWOT analysis has some limitations as it is unable to prioritize appropriately the multiple alternative strategic decisions. Some efforts have been made to solve this problem by incorporating Multi Criteria Decision Making (MCDM) methods. Nevertheless, another important aspect has raised concerns on obtaining the decision that is the reliability of the information. Decision makers evaluate differently depending on their level of confidence or sureness in the evaluation. This study proposes a decision making procedure for strategic planning using SWOT-TOPSIS method by incorporating the reliability factor of the evaluation based on Z-number. An example using a local authority in the east coast of Malaysia is illustrated to determine the strategic options ranking and to prioritize factors in each SWOT category.

  8. BAC Modification through Serial or Simultaneous Use of CRE/Lox Technology

    PubMed Central

    Parrish, Mark; Unruh, Jay; Krumlauf, Robb

    2011-01-01

    Bacterial Artificial Chromosomes (BACs) are vital tools in mouse genomic analyses because of their ability to propagate large inserts. The size of these constructs, however, prevents the use of conventional molecular biology techniques for modification and manipulation. Techniques such as recombineering and Cre/Lox methodologies have thus become heavily relied upon for such purposes. In this work, we investigate the applicability of Lox variant sites for serial and/or simultaneous manipulations of BACs. We show that Lox spacer mutants are very specific, and inverted repeat variants reduce Lox reaction rates through reducing the affinity of Cre for the site, while retaining some functionality. Employing these methods, we produced serial modifications encompassing four independent changes which generated a mouse HoxB BAC with fluorescent reporter proteins inserted into four adjacent Hox genes. We also generated specific, simultaneous deletions using combinations of spacer variants and inverted repeat variants. These techniques will facilitate BAC manipulations and open a new repertoire of methods for BAC and genome manipulation. PMID:21197414

  9. Generating mouse models of degenerative diseases using Cre/lox-mediated in vivo mosaic cell ablation

    PubMed Central

    Fujioka, Masato; Tokano, Hisashi; Fujioka, Keiko Shiina; Okano, Hideyuki; Edge, Albert S.B.

    2011-01-01

    Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies. PMID:21576819

  10. The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization.

    PubMed

    Romero-López, Cristina; Barroso-delJesus, Alicia; Berzal-Herranz, Alfredo

    2017-02-24

    The RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3'UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2'-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome.

  11. The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization

    PubMed Central

    Romero-López, Cristina; Barroso-delJesus, Alicia; Berzal-Herranz, Alfredo

    2017-01-01

    The RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3′UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2′-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome. PMID:28233845

  12. Mouse model of proximal colon-specific tumorigenesis driven by microsatellite instability-induced Cre-mediated inactivation of Apc and activation of Kras.

    PubMed

    Kawaguchi, Yasuo; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Miguchi, Masashi; Niitsu, Hiroaki; Sasada, Tatsunari; Shimomura, Manabu; Egi, Hiroyuki; Oka, Shiro; Tanaka, Shinji; Chayama, Kazuaki; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki

    2016-05-01

    KRAS gene mutations are found in 40-50% of colorectal cancer cases, but their functional contribution is not fully understood. To address this issue, we generated genetically engineered mice with colon tumors expressing an oncogenic Kras(G12D) allele in the context of the Adenomatous polyposis coli (Apc) deficiency to compare them to tumors harboring Apc deficiency alone. CDX2P9.5-G22Cre (referred to as G22Cre) mice showing inducible Cre recombinase transgene expression in the proximal colon controlled under the CDX2 gene promoter were intercrossed with Apc (flox/flox) mice and LSL-Kras (G12D) mice carrying loxP-flanked Apc and Lox-Stop-Lox oncogenic Kras(G12D) alleles, respectively, to generate G22Cre; Apc(flox/flox); Kras(G12D) and G22Cre; Apc(flox/flox); KrasWT mice. Gene expression profiles of the tumors were analyzed using high-density oligonucleotide arrays. Morphologically, minimal difference in proximal colon tumor was observed between the two mouse models. Consistent with previous findings in vitro, Glut1 transcript and protein expression was up-regulated in the tumors of G22Cre;Apc (flox/flox) ; Kras(G12D) mice. Immunohistochemical staining analysis revealed that GLUT1 protein expression correlated with KRAS mutations in human colorectal cancer. Microarray analysis identified 11 candidate genes upregulated more than fivefold and quantitative PCR analysis confirmed that Aqp8, Ttr, Qpct, and Slc26a3 genes were upregulated 3.7- to 30.2-fold in tumors with mutant Kras. These results demonstrated the validity of the G22Cre; Apc(flox/flox) ;Kras (G12D) mice as a new mouse model with oncogenic Kras activation. We believe that this model can facilitate efforts to define novel factors that contribute to the pathogenesis of human colorectal cancer with KRAS mutations.

  13. California Community Colleges Technology II Strategic Plan, 2000-2005.

    ERIC Educational Resources Information Center

    California Community Colleges, Sacramento. Office of the Chancellor.

    This Strategic Plan aims to address the issues facing California Community Colleges (CCCs) due to new technology. The issues raised by the report include: (1) the pervasive and economically and socially necessary use of the Internet; (2) the digital divide; (3) the need for integrating technology into teaching and learning; (4) the impact of Tidal…

  14. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development

    PubMed Central

    McCann, Matthew R.; Tamplin, Owen J.; Rossant, Janet; Séguin, Cheryle A.

    2012-01-01

    SUMMARY Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration. PMID:22028328

  15. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

    PubMed

    McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

    2012-01-01

    Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

  16. Simultaneous and Sequential Integration by Cre/loxP Site-Specific Recombination in Saccharomyces cerevisiae.

    PubMed

    Choi, Ho-Jung; Kim, Yeon-Hee

    2018-05-28

    A Cre/ loxP -δ-integration system was developed to allow sequential and simultaneous integration of a multiple gene expression cassette in Saccharomyces cerevisiae . To allow repeated integrations, the reusable Candida glabrata MARKER ( CgMARKER ) carrying loxP sequences was used, and the integrated CgMARKER was efficiently removed by inducing Cre recombinase. The XYLP and XYLB genes encoding endoxylanase and β-xylosidase, respectively, were used as model genes for xylan metabolism in this system, and the copy number of these genes was increased to 15.8 and 16.9 copies/cell, respectively, by repeated integration. This integration system is a promising approach for the easy construction of yeast strains with enhanced metabolic pathways through multicopy gene expression.

  17. Improved α-Amylase Production by Dephosphorylation Mutation of CreD, an Arrestin-Like Protein Required for Glucose-Induced Endocytosis of Maltose Permease and Carbon Catabolite Derepression in Aspergillus oryzae

    PubMed Central

    Tanaka, Mizuki; Hiramoto, Tetsuya; Tada, Hinako; Shintani, Takahiro

    2017-01-01

    ABSTRACT Aspergillus oryzae produces copious amount of amylolytic enzymes, and MalP, a major maltose permease, is required for the expression of amylase-encoding genes. The expression of these genes is strongly repressed by carbon catabolite repression (CCR) in the presence of glucose. MalP is transported from the plasma membrane to the vacuole by endocytosis, which requires the homolog of E6-AP carboxyl terminus ubiquitin ligase HulA, an ortholog of yeast Rsp5. In yeast, arrestin-like proteins mediate endocytosis as adaptors of Rsp5 and transporters. In the present study, we examined the involvement of CreD, an arrestin-like protein, in glucose-induced MalP endocytosis and CCR of amylase-encoding genes. Deletion of creD inhibited the glucose-induced endocytosis of MalP, and CreD showed physical interaction with HulA. Phosphorylation of CreD was detected by Western blotting, and two serine residues were determined as the putative phosphorylation sites. However, the phosphorylation state of the serine residues did not regulate MalP endocytosis and its interaction with HulA. Although α-amylase production was significantly repressed by creD deletion, both phosphorylation and dephosphorylation mimics of CreD had a negligible effect on α-amylase activity. Interestingly, dephosphorylation of CreD was required for CCR relief of amylase genes that was triggered by disruption of the deubiquitinating enzyme-encoding gene creB. The α-amylase activity of the creB mutant was 1.6-fold higher than that of the wild type, and the dephosphorylation mimic of CreD further improved the α-amylase activity by 2.6-fold. These results indicate that a combination of the dephosphorylation mutation of CreD and creB disruption increased the production of amylolytic enzymes in A. oryzae. IMPORTANCE In eukaryotes, glucose induces carbon catabolite repression (CCR) and proteolytic degradation of plasma membrane transporters via endocytosis. Glucose-induced endocytosis of transporters is

  18. Improved α-Amylase Production by Dephosphorylation Mutation of CreD, an Arrestin-Like Protein Required for Glucose-Induced Endocytosis of Maltose Permease and Carbon Catabolite Derepression in Aspergillus oryzae.

    PubMed

    Tanaka, Mizuki; Hiramoto, Tetsuya; Tada, Hinako; Shintani, Takahiro; Gomi, Katsuya

    2017-07-01

    Aspergillus oryzae produces copious amount of amylolytic enzymes, and MalP, a major maltose permease, is required for the expression of amylase-encoding genes. The expression of these genes is strongly repressed by carbon catabolite repression (CCR) in the presence of glucose. MalP is transported from the plasma membrane to the vacuole by endocytosis, which requires the homolog of E6-AP carboxyl terminus ubiquitin ligase HulA, an ortholog of yeast Rsp5. In yeast, arrestin-like proteins mediate endocytosis as adaptors of Rsp5 and transporters. In the present study, we examined the involvement of CreD, an arrestin-like protein, in glucose-induced MalP endocytosis and CCR of amylase-encoding genes. Deletion of creD inhibited the glucose-induced endocytosis of MalP, and CreD showed physical interaction with HulA. Phosphorylation of CreD was detected by Western blotting, and two serine residues were determined as the putative phosphorylation sites. However, the phosphorylation state of the serine residues did not regulate MalP endocytosis and its interaction with HulA. Although α-amylase production was significantly repressed by creD deletion, both phosphorylation and dephosphorylation mimics of CreD had a negligible effect on α-amylase activity. Interestingly, dephosphorylation of CreD was required for CCR relief of amylase genes that was triggered by disruption of the deubiquitinating enzyme-encoding gene creB The α-amylase activity of the creB mutant was 1.6-fold higher than that of the wild type, and the dephosphorylation mimic of CreD further improved the α-amylase activity by 2.6-fold. These results indicate that a combination of the dephosphorylation mutation of CreD and creB disruption increased the production of amylolytic enzymes in A. oryzae IMPORTANCE In eukaryotes, glucose induces carbon catabolite repression (CCR) and proteolytic degradation of plasma membrane transporters via endocytosis. Glucose-induced endocytosis of transporters is mediated by

  19. DNA cytosine methylation in the bovine leukemia virus promoter is associated with latency in a lymphoma-derived B-cell line: potential involvement of direct inhibition of cAMP-responsive element (CRE)-binding protein/CRE modulator/activation transcription factor binding.

    PubMed

    Pierard, Valérie; Guiguen, Allan; Colin, Laurence; Wijmeersch, Gaëlle; Vanhulle, Caroline; Van Driessche, Benoît; Dekoninck, Ann; Blazkova, Jana; Cardona, Christelle; Merimi, Makram; Vierendeel, Valérie; Calomme, Claire; Nguyên, Thi Liên-Anh; Nuttinck, Michèle; Twizere, Jean-Claude; Kettmann, Richard; Portetelle, Daniel; Burny, Arsène; Hirsch, Ivan; Rohr, Olivier; Van Lint, Carine

    2010-06-18

    Bovine leukemia virus (BLV) proviral latency represents a viral strategy to escape the host immune system and allow tumor development. Besides the previously demonstrated role of histone deacetylation in the epigenetic repression of BLV expression, we showed here that BLV promoter activity was induced by several DNA methylation inhibitors (such as 5-aza-2'-deoxycytidine) and that overexpressed DNMT1 and DNMT3A, but not DNMT3B, down-regulated BLV promoter activity. Importantly, cytosine hypermethylation in the 5'-long terminal repeat (LTR) U3 and R regions was associated with true latency in the lymphoma-derived B-cell line L267 but not with defective latency in YR2 cells. Moreover, the virus-encoded transactivator Tax(BLV) decreased DNA methyltransferase expression levels, which could explain the lower level of cytosine methylation observed in the L267(LTaxSN) 5'-LTR compared with the L267 5'-LTR. Interestingly, DNA methylation inhibitors and Tax(BLV) synergistically activated BLV promoter transcriptional activity in a cAMP-responsive element (CRE)-dependent manner. Mechanistically, methylation at the -154 or -129 CpG position (relative to the transcription start site) impaired in vitro binding of CRE-binding protein (CREB) transcription factors to their respective CRE sites. Methylation at -129 CpG alone was sufficient to decrease BLV promoter-driven reporter gene expression by 2-fold. We demonstrated in vivo the recruitment of CREB/CRE modulator (CREM) and to a lesser extent activating transcription factor-1 (ATF-1) to the hypomethylated CRE region of the YR2 5'-LTR, whereas we detected no CREB/CREM/ATF recruitment to the hypermethylated corresponding region in the L267 cells. Altogether, these findings suggest that site-specific DNA methylation of the BLV promoter represses viral transcription by directly inhibiting transcription factor binding, thereby contributing to true proviral latency.

  20. Controlled Cre/loxP Site-Specific Recombination in the Developing Brain in Medaka Fish, Oryzias latipes

    PubMed Central

    Okuyama, Teruhiro; Isoe, Yasuko; Hoki, Masahito; Suehiro, Yuji; Yamagishi, Genki; Naruse, Kiyoshi; Kinoshita, Masato; Kamei, Yasuhiro; Shimizu, Atushi; Kubo, Takeo; Takeuchi, Hideaki

    2013-01-01

    Background Genetic mosaic techniques have been used to visualize and/or genetically modify a neuronal subpopulation within complex neural circuits in various animals. Neural populations available for mosaic analysis, however, are limited in the vertebrate brain. Methodology/Principal Findings To establish methodology to genetically manipulate neural circuits in medaka, we first created two transgenic (Tg) medaka lines, Tg (HSP:Cre) and Tg (HuC:loxP-DsRed-loxP-GFP). We confirmed medaka HuC promoter-derived expression of the reporter gene in juvenile medaka whole brain, and in neuronal precursor cells in the adult brain. We then demonstrated that stochastic recombination can be induced by micro-injection of Cre mRNA into Tg (HuC:loxP-DsRed-loxP-GFP) embryos at the 1-cell stage, which allowed us to visualize some subpopulations of GFP-positive cells in compartmentalized regions of the telencephalon in the adult medaka brain. This finding suggested that the distribution of clonally-related cells derived from single or a few progenitor cells was restricted to a compartmentalized region. Heat treatment of Tg(HSP:Cre x HuC:loxP-DsRed-loxP-GFP) embryos (0–1 day post fertilization [dpf]) in a thermalcycler (39°C) led to Cre/loxP recombination in the whole brain. The recombination efficiency was notably low when using 2–3 dpf embyos compared with 0–1 dpf embryos, indicating the possibility of stage-dependent sensitivity of heat-inducible recombination. Finally, using an infrared laser-evoked gene operator (IR-LEGO) system, heat shock induced in a micro area in the developing brains led to visualization of clonally-related cells in both juvenile and adult medaka fish. Conclusions/Significance We established a noninvasive method to control Cre/loxP site-specific recombination in the developing nervous system in medaka fish. This method will broaden the neural population available for mosaic analyses and allow for lineage tracing of the vertebrate nervous system in both

  1. Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti.

    PubMed

    Häcker, Irina; Harrell Ii, Robert A; Eichner, Gerrit; Pilitt, Kristina L; O'Brochta, David A; Handler, Alfred M; Schetelig, Marc F

    2017-03-07

    Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

  2. Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

    PubMed

    Condie, Brian G; Urbanski, William M

    2014-01-01

    Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

  3. How Strategic Presidential Leadership and Institutional Culture Influenced Fund-Raising Effectiveness at Spelman College

    ERIC Educational Resources Information Center

    Barrett, T. Gregory

    2006-01-01

    How have presidential leadership strategy, decision approaches, and institutional culture preferences influenced fund-raising effectiveness at a historically Black college for women? These conceptual dimensions guided a qualitative study that interviewed three recent Spelman College presidents and investigated documentary evidence to develop an…

  4. Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47.

    PubMed

    de Assis, Leandro José; Ulas, Mevlut; Ries, Laure Nicolas Annick; El Ramli, Nadia Ali Mohamed; Sarikaya-Bayram, Ozlem; Braus, Gerhard H; Bayram, Ozgur; Goldman, Gustavo Henrique

    2018-06-19

    The attachment of one or more ubiquitin molecules by SCF ( S kp- C ullin- F -box) complexes to protein substrates targets them for subsequent degradation by the 26S proteasome, allowing the control of numerous cellular processes. Glucose-mediated signaling and subsequent carbon catabolite repression (CCR) are processes relying on the functional regulation of target proteins, ultimately controlling the utilization of this carbon source. In the filamentous fungus Aspergillus nidulans , CCR is mediated by the transcription factor CreA, which modulates the expression of genes encoding biotechnologically relevant enzymes. Although CreA-mediated repression of target genes has been extensively studied, less is known about the regulatory pathways governing CCR and this work aimed at further unravelling these events. The Fbx23 F-box protein was identified as being involved in CCR and the Δ fbx23 mutant presented impaired xylanase production under repressing (glucose) and derepressing (xylan) conditions. Mass spectrometry showed that Fbx23 is part of an SCF ubiquitin ligase complex that is bridged via the GskA protein kinase to the CreA-SsnF-RcoA repressor complex, resulting in the degradation of the latter under derepressing conditions. Upon the addition of glucose, CreA dissociates from the ubiquitin ligase complex and is transported into the nucleus. Furthermore, casein kinase is important for CreA function during glucose signaling, although the exact role of phosphorylation in CCR remains to be determined. In summary, this study unraveled novel mechanistic details underlying CreA-mediated CCR and provided a solid basis for studying additional factors involved in carbon source utilization which could prove useful for biotechnological applications. IMPORTANCE The production of biofuels from plant biomass has gained interest in recent years as an environmentally friendly alternative to production from petroleum-based energy sources. Filamentous fungi, which naturally

  5. A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

    PubMed Central

    Sabbah, Shai

    2017-01-01

    Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070

  6. Cre/lox system to develop selectable marker free transgenic tobacco plants conferring resistance against sap sucking homopteran insect.

    PubMed

    Chakraborti, Dipankar; Sarkar, Anindya; Mondal, Hossain A; Schuermann, David; Hohn, Barbara; Sarmah, Bidyut K; Das, Sampa

    2008-10-01

    A binary expression vector was constructed containing the insecticidal gene Allium sativum leaf agglutinin (ASAL), and a selectable nptII marker gene cassette, flanked by lox sites. Similarly, another binary vector was developed with the chimeric cre gene construct. Transformed tobacco plants were generated with these two independent vectors. Each of the T(0) lox plants was crossed with T(0) Cre plants. PCR analyses followed by the sequencing of the target T-DNA part of the hybrid T(1) plants demonstrated the excision of the nptII gene in highly precised manner in certain percentage of the T(1) hybrid lines. The frequency of such marker gene excision was calculated to be 19.2% in the hybrids. Marker free plants were able to express ASAL efficiently and reduce the survivability of Myzus persiceae, the deadly pest of tobacco significantly, compared to the control tobacco plants. Results of PCR and Southern blot analyses of some of the T(2) plants detected the absence of cre as well as nptII genes. Thus, the crossing strategy involving Cre/lox system for the excision of marker genes appears to be very effective and easy to execute. Documentation of such marker excision phenomenon in the transgenic plants expressing the important insecticidal protein for the first time has a great significance from agricultural and biotechnological points of view.

  7. Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells.

    PubMed

    Long, Qifang; Yang, Ru; Lu, Weixian; Zhu, Weipei; Zhou, Jundong; Zheng, Cui; Zhou, Dongmei; Yu, Ling; Wu, Jinchang

    2017-01-01

    Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.

  8. IT strategic planning in hospitals: from theory to practice.

    PubMed

    Jaana, Mirou; Teitelbaum, Mari; Roffey, Tyson

    2014-07-01

    To date, IT strategic planning has been mostly theory-based with limited information on "best practices" in this area. This study presents the process and outcomes of IT strategic planning undertaken at a pediatric hospital (PH) in Canada. A five-stage sequential and incremental process was adopted. Various tools / approaches were used including review of existing documentation, internal survey (n = 111), fifteen interviews, and twelve workshops. IT strategic planning was informed by 230 individuals (12 percent of hospital community) and revealed consistency in the themes and concerns raised by participants (e.g., slow IT projects delivery rate, lack of understanding of IT priorities, strained communication with IT staff). Mobile and remote access to patients' information, and an integrated EMR were identified as top priorities. The methodology and used approach revealed effective, improved internal relationships, and ensured commitment to the final IT strategic plan. Several lessons were learned including: maintaining a dynamic approach capable of adapting to the fast technology evolution; involving stakeholders and ensuring continuous communication; using effective research tools to support strategic planning; and grounding the process and final product in existing models. This study contributes to the development of "best practices" in IT strategic planning, and illustrates "how" to apply the theoretical principles in this area. This is especially important as IT leaders are encouraged to integrate evidence-based management into their decision making and practices. The methodology and lessons learned may inform practitioners in other hospitals planning to engage in IT strategic planning in the future.

  9. v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

    PubMed

    Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

    1994-10-01

    We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

  10. Lactoferricin B Inhibits the Phosphorylation of the Two-Component System Response Regulators BasR and CreB*

    PubMed Central

    Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

    2012-01-01

    Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly. PMID:22138548

  11. Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB.

    PubMed

    Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

    2012-04-01

    Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly.

  12. Mining the protein data bank with CReF to predict approximate 3-D structures of polypeptides.

    PubMed

    Dorn, Márcio; de Souza, Osmar Norberto

    2010-01-01

    n this paper we describe CReF, a Central Residue Fragment-based method to predict approximate 3-D structures of polypeptides by mining the Protein Data Bank (PDB). The approximate predicted structures are good enough to be used as starting conformations in refinement procedures employing state-of-the-art molecular mechanics methods such as molecular dynamics simulations. CReF is very fast and we illustrate its efficacy in three case studies of polypeptides whose sizes vary from 34 to 70 amino acids. As indicated by the RMSD values, our initial results show that the predicted structures adopt the expected fold, similar to the experimental ones.

  13. Genetically Targeted All-Optical Electrophysiology with a Transgenic Cre-Dependent Optopatch Mouse

    PubMed Central

    Lou, Shan; Adam, Yoav; Weinstein, Eli N.; Williams, Erika; Williams, Katherine; Parot, Vicente; Kavokine, Nikita; Liberles, Stephen; Madisen, Linda; Zeng, Hongkui

    2016-01-01

    Recent advances in optogenetics have enabled simultaneous optical perturbation and optical readout of membrane potential in diverse cell types. Here, we develop and characterize a Cre-dependent transgenic Optopatch2 mouse line that we call Floxopatch. The animals expressed a blue-shifted channelrhodopsin, CheRiff, and a near infrared Archaerhodopsin-derived voltage indicator, QuasAr2, via targeted knock-in at the rosa26 locus. In Optopatch-expressing animals, we tested for overall health, genetically targeted expression, and function of the optogenetic components. In offspring of Floxopatch mice crossed with a variety of Cre driver lines, we observed spontaneous and optically evoked activity in vitro in acute brain slices and in vivo in somatosensory ganglia. Cell-type-specific expression allowed classification and characterization of neuronal subtypes based on their firing patterns. The Floxopatch mouse line is a useful tool for fast and sensitive characterization of neural activity in genetically specified cell types in intact tissue. SIGNIFICANCE STATEMENT Optical recordings of neural activity offer the promise of rapid and spatially resolved mapping of neural function. Calcium imaging has been widely applied in this mode, but is insensitive to the details of action potential waveforms and subthreshold events. Simultaneous optical perturbation and optical readout of single-cell electrical activity (“Optopatch”) has been demonstrated in cultured neurons and in organotypic brain slices, but not in acute brain slices or in vivo. Here, we describe a transgenic mouse in which expression of Optopatch constructs is controlled by the Cre-recombinase enzyme. This animal enables fast and robust optical measurements of single-cell electrical excitability in acute brain slices and in somatosensory ganglia in vivo, opening the door to rapid optical mapping of neuronal excitability. PMID:27798186

  14. Raising Student Achievement in the Dayton Public Schools. Report of the Dayton Public Schools Strategic Support Teams.

    ERIC Educational Resources Information Center

    Council of the Great City Schools, Washington, DC.

    This report describes the Dayton Public Schools Strategic Support Teams (SSTs), which address stagnant student achievement among Dayton's students. They are composed of superintendents and other senior urban school managers from across the country who have struggled with the same issues as Dayton. Chapter 1 summarizes SST findings about challenges…

  15. Production of transgenic pigs using a pGFAP-CreERT2/EGFP LoxP inducible system for central nervous system disease models.

    PubMed

    Hwang, Seon-Ung; Eun, Kiyoung; Yoon, Junchul David; Kim, Hyunggee; Hyun, Sang-Hwan

    2018-05-31

    Transgenic (TG) pigs are important in biomedical research and are used in disease modeling, pharmaceutical toxicity testing, and regenerative medicine. In this study, we constructed two vector systems by using the promoter of the pig glial fibrillary acidic protein ( pGFAP ) gene, which is an astrocyte cell marker. We established donor TG fibroblasts with pGFAP-CreER T2 /LCMV-EGFP LoxP and evaluated the effect of the transgenes on TG-somatic cell nuclear transfer (SCNT) embryo development. Cleavage rates were not significantly different between control and transgene-donor groups. Embryo transfer was performed thrice just before ovulation of the surrogate sows. One sow delivered 5 TG piglets at 115 days after pregnancy. Polymerase chain reaction (PCR) analysis with genomic DNA isolated from skin tissues of TG pigs revealed that all 5 TG pigs had the transgenes. EGFP expression in all organs tested was confirmed by immunofluorescence staining and PCR. Real-time PCR analysis showed that pGFAP promoter-driven Cre fused to the mutated human ligand-binding domain of the estrogen receptor ( CreER T2 ) mRNA was highly expressed in the cerebrum. Semi-nested PCR analysis revealed that CreER T2 -mediated recombination was induced in cerebrum and cerebellum but not in skin. Thus, we successfully generated a TG pig with a 4-hydroxytamoxifen (TM)-inducible pGFAP-CreER T2 /EGFP LoxP recombination system via SCNT.

  16. Foxc2CreERT2 knock-in mice mark stage-specific Foxc2-expressing cells during mouse organogenesis.

    PubMed

    Amin, Mohammed Badrul; Miura, Naoyuki; Uddin, Mohammad Khaja Mafij; Islam, Mohammod Johirul; Yoshida, Nobuaki; Iseki, Sachiko; Kume, Tsutomu; Trainor, Paul A; Saitsu, Hirotomo; Aoto, Kazushi

    2017-01-01

    Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2 CreERT2 ) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2 CreERT2 ; R26R), the fate of Foxc2 positive (Foxc2 + ) cells was analyzed through LacZ staining at various embryonic stages. We found Foxc2 + cell descendants in the supraoccipital and exoccipital bone in E18.5 embryos, when tamoxifen was administered at embryonic day (E) 8.5. Furthermore, Foxc2 + descendant cranial neural crest cells at E8-10 were restricted to the corneal mesenchyme, while Foxc2 + cell derived cardiac neural crest cells at E6-12 were found in the aorta, pulmonary trunk and valves, and endocardial cushions. Foxc2 + cell descendant contributions to the glomerular podocytes in the kidney were also observed following E6.5 tamoxifen treatment. Our results are consistent with previous reports of Foxc2 expression during early embryogenesis and the Foxc2 CreERT2 mouse provides a tool to investigate spatiotemporal roles of Foxc2 and contributions of Foxc2 + expressing cells during mouse embryogenesis. © 2016 Japanese Teratology Society.

  17. Cognitive Characteristics of Strategic and Non-strategic Gamblers.

    PubMed

    Mouneyrac, Aurélie; Lemercier, Céline; Le Floch, Valérie; Challet-Bouju, Gaëlle; Moreau, Axelle; Jacques, Christian; Giroux, Isabelle

    2018-03-01

    Participation in strategic and non-strategic games is mostly explained in the literature by gender: men gamble on strategic games, while women gamble on non-strategic games. However, little is known about the underlying cognitive factors that could also distinguish strategic and non-strategic gamblers. We suggest that cognitive style and need for cognition also explain participation in gambling subtypes. From a dual-process perspective, cognitive style is the tendency to reject or accept the fast, automatic answer that comes immediately in response to a problem. Individuals that preferentially reject the automatic response use an analytic style, which suggest processing information in a slow way, with deep treatment. The intuitive style supposes a reliance on fast, automatic answers. The need for cognition provides a motivation to engage in effortful activities. One hundred and forty-nine gamblers (53 strategic and 96 non-strategic) answered the Cognitive Reflection Test, Need For Cognition Scale, and socio-demographic questions. A logistic regression was conducted to evaluate the influence of gender, cognitive style and need for cognition on participation in strategic and non-strategic games. Our results show that a model with both gender and cognitive variables is more accurate than a model with gender alone. Analytic (vs. intuitive) style, high (vs. low) need for cognition and being male (vs. female) are characteristics of strategic gamblers (vs. non-strategic gamblers). This study highlights the importance of considering the cognitive characteristics of strategic and non-strategic gamblers in order to develop preventive campaigns and treatments that fit the best profiles for gamblers.

  18. Puromycin and Methotrexate Resistance Cassettes and Optimized cre-recombinase Expression Plasmids for use in Yeast

    PubMed Central

    MacDonald, Chris; Piper, Robert C.

    2015-01-01

    Here we expand the set of tools for genetically manipulating Saccharomyces cerevisiae. We show that puromycin-resistance can be achieved in yeast through expression of a bacterial puromycin-resistance gene optimized to the yeast codon bias, which in turn serves as an easy to use dominant genetic marker suitable for gene disruption. We have constructed a similar DNA cassette expressing yeast codon-optimized mutant human dihydrofolate reductase (DHFR) that confers resistance to methotrexate and can also be used as a dominant selectable marker. Both of these drug-resistant marker cassettes are flanked by loxP sites allowing for their excision from the genome following expression of cre-recombinase. Finally, we have created a series of plasmids for low-level constitutive expression of cre-recombinase in yeast that allows for efficient excision of loxP-flanked markers. PMID:25688547

  19. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

    PubMed Central

    Deverman, Benjamin E.; Pravdo, Piers L.; Simpson, Bryan P.; Kumar, Sripriya Ravindra; Chan, Ken Y.; Banerjee, Abhik; Wu, Wei-Li; Yang, Bin; Huber, Nina; Pasca, Sergiu P.; Gradinaru, Viviana

    2015-01-01

    Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer1-6. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics7-13. Here we describe a capsid selection method, called Cre-recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV914-17, and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications. PMID:26829320

  20. Carbapenem-resistant Enterobacteriaceae (CRE) or Delayed Appropriate Therapy (DAT)—Does One Affect Outcomes More Than the Other Among Patients With Serious Infections Due to Enterobacteriaceae?

    PubMed Central

    Lodise, Thomas; Berger, Ariel; Altincatal, Arman; Wang, Rosa; Bhagnani, Tarun; Gillard, Patrick; Bonine, Nicole G

    2017-01-01

    Abstract Background While CRE and DAT are both associated with worse outcomes, their relative impact to the clinical and economic burden among patients with infections due to Enterobacteriaceae is not well understood. This study assessed the independent and combined effect of these two items on selected outcomes among patients with these infections. Methods Hospitalized adults between July 2011 and September 2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for Enterobacteriaceae from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. CRE was defined as resistant to ≥1 carbapenems. Inverse probability weighting and multivariate regression analyses were used to estimate the associations between CRE status, DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice), in-hospital mortality, and discharge to home (reference group was timely therapy plus non-CRE); generalized linear models, for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs. Results A total of 50,069 patients were included in the analyses; 514 had CRE and 16,414 received DAT. A gradient effect was observed across strata as the burden of serious infections was least among the reference group, and greatest among patients with CRE infection who received DAT (Figure). For example, as compared with the reference group, the risk of composite mortality increased nearly fourfold in patients with CRE infection who received DAT; total in-hospital costs more than doubled. Conclusion DAT has a stronger association than CRE on

  1. Tamoxifen Activation of Cre-Recombinase Has No Persisting Effects on Adult Neurogenesis or Learning and Anxiety

    PubMed Central

    Rotheneichner, Peter; Romanelli, Pasquale; Bieler, Lara; Pagitsch, Sebastian; Zaunmair, Pia; Kreutzer, Christina; König, Richard; Marschallinger, Julia; Aigner, Ludwig; Couillard-Després, Sébastien

    2017-01-01

    Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreERT2-Lox system are widely used. In this study, we made use of a Nestin-CreERT2/R26R-YFP transgenic mouse model in which the CreERT2 activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis. The application of tamoxifen, a mixed agonist/antagonist of the estrogen receptor that permeates the blood-brain-barrier, could thus influence adult neurogenesis. Although the functions of adult neurogenesis are yet to be fully deciphered, a reciprocal interaction between rates of neurogenesis on the one hand and learning and mood regulation on the other hand, has been suggested. The impact of tamoxifen on neurogenesis and behavior was therefore addressed following five daily applications according to the open field test, the elevated plus maze, and Morris water maze. In addition, the impact of short-term tamoxifen application on progenitor cell proliferation, morphology, and fate in the neurogenic niche of the dentate gyrus were investigated. Finally, the influence of the route of administration (oral vs. intra-peritoneal) and gender-specific response were scrutinized. The sub-acute analysis did neither reveal significant differences in behavior, such as voluntary motor activity, anxiety behavior, and spatial learning, nor in cell proliferation, cell survival, dendritic arborization or maturation rate within the dentate gyrus between saline solution-, corn oil-, and tamoxifen-treated groups. Finally, neither the route of application, nor the gender of treated mice influenced the response to tamoxifen. We conclude that short tamoxifen treatments used to activate the CreERT2 system in transgenic mouse models does not have a

  2. Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor.

    PubMed

    Bayguinov, Peter O; Ma, Yihe; Gao, Yu; Zhao, Xinyu; Jackson, Meyer B

    2017-09-20

    Genetically encoded voltage indicators create an opportunity to monitor electrical activity in defined sets of neurons as they participate in the complex patterns of coordinated electrical activity that underlie nervous system function. Taking full advantage of genetically encoded voltage indicators requires a generalized strategy for targeting the probe to genetically defined populations of cells. To this end, we have generated a mouse line with an optimized hybrid voltage sensor (hVOS) probe within a locus designed for efficient Cre recombinase-dependent expression. Crossing this mouse with Cre drivers generated double transgenics expressing hVOS probe in GABAergic, parvalbumin, and calretinin interneurons, as well as hilar mossy cells, new adult-born neurons, and recently active neurons. In each case, imaging in brain slices from male or female animals revealed electrically evoked optical signals from multiple individual neurons in single trials. These imaging experiments revealed action potentials, dynamic aspects of dendritic integration, and trial-to-trial fluctuations in response latency. The rapid time response of hVOS imaging revealed action potentials with high temporal fidelity, and enabled accurate measurements of spike half-widths characteristic of each cell type. Simultaneous recording of rapid voltage changes in multiple neurons with a common genetic signature offers a powerful approach to the study of neural circuit function and the investigation of how neural networks encode, process, and store information. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators hold great promise in the study of neural circuitry, but realizing their full potential depends on targeting the sensor to distinct cell types. Here we present a new mouse line that expresses a hybrid optical voltage sensor under the control of Cre recombinase. Crossing this line with Cre drivers generated double-transgenic mice, which express this sensor in targeted cell types. In

  3. Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice

    PubMed Central

    Yun, Sanghee; Donovan, Michael H.; Ross, Michele N.; Richardson, Devon R.; Reister, Robin; Farnbauch, Laure A.; Fischer, Stephanie J.; Riethmacher, Dieter; Gershenfeld, Howard K.; Lagace, Diane C.; Eisch, Amelia J.

    2016-01-01

    Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient–rather than permanent–inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreERT2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12–30 days post-TAM displayed indices of a stress-induced anxiety phenotype–longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype–longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety

  4. A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

    PubMed

    Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K

    2015-04-01

    Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

  5. Plasma is a strategic resource.

    PubMed

    Strengers, Paul F W; Klein, Harvey G

    2016-12-01

    Plasma-derived medicinal products (PDMPs) such as immunoglobulins and clotting factors are listed by the World Health Organization as essential medicines. These and other PDMPs are crucial for the prophylaxis and treatment of patients with bleeding disorders, immune deficiencies, autoimmune and inflammatory diseases, and a variety of congenital deficiency disorders. While changes in clinical practice in developed countries have reduced the need for red blood cell transfusions thereby significantly reducing the collection volumes of whole blood and recovered plasma suitable for fractionation, the need for PDMPs worldwide continues to increase. The majority of plasma supplies for the manufacture of PDMPs is met by the US commercial plasma industry. However, geographic imbalance in the collection of plasma raises concerns that local disruptions of plasma supplies could result in regional and global shortages of essential PDMPs. Plasma, which fits the definition of a strategic resource, that is, "an economically important raw material which is subject to a higher risk of supply interruption," should be considered a strategic resource comparable to energy and drinking water. Plasma collections should be increased outside the United States, including in low- and middle-income countries. The need for capacity building in these countries is an essential part to strengthen quality plasma collection. This will require changes in national and regional policies. We advocate the need for the restoration of an equitable balance of the international plasma supply to reduce the risk of supply shortages worldwide. Strategic independence of plasma should be endorsed on a global level. © 2016 AABB.

  6. Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.

    PubMed

    Franckaert, Dean; Dooley, James; Roos, Evelyne; Floess, Stefan; Huehn, Jochen; Luche, Herve; Fehling, Hans Joerg; Liston, Adrian; Linterman, Michelle A; Schlenner, Susan M

    2015-04-01

    Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including R26-RFP). This hypomorphism and 'leaky' expression of the Foxp3-CreYFP allele should be considered when analysing the conditionally mutated Treg.

  7. BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear organotypic cultures from deaf Cx26Sox10Cre mice.

    PubMed

    Crispino, Giulia; Di Pasquale, Giovanni; Scimemi, Pietro; Rodriguez, Laura; Galindo Ramirez, Fabian; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo; Bortolozzi, Mario; Chiorini, John A; Mammano, Fabio

    2011-01-01

    The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.

  8. Generation of knock-in mice that express nuclear enhanced green fluorescent protein and tamoxifen-inducible Cre recombinase in the notochord from Foxa2 and T loci.

    PubMed

    Imuta, Yu; Kiyonari, Hiroshi; Jang, Chuan-Wei; Behringer, Richard R; Sasaki, Hiroshi

    2013-03-01

    The node and the notochord are important embryonic signaling centers that control embryonic pattern formation. Notochord progenitor cells present in the node and later in the posterior end of the notochord move anteriorly to generate the notochord. To understand the dynamics of cell movement during notochord development and the molecular mechanisms controlling this event, analyses of cell movements using time-lapse imaging and conditional manipulation of gene activities are required. To achieve this goal, we generated two knock-in mouse lines that simultaneously express nuclear enhanced green fluorescent protein (EGFP) and tamoxifen-inducible Cre, CreER(T2) , from two notochord gene loci, Foxa2 and T (Brachury). In Foxa2(nEGFP-CreERT2/+) and T(nEGFP-CreERT2/+) embryos, nuclei of the Foxa2 or T-expressing cells, which include the node, notochord, and endoderm (Foxa2) or wide range of posterior mesoderm (T), were labeled with EGFP at intensities that can be used for live imaging. Cre activity was also induced in cells expressing Foxa2 and T 1 day after tamoxifen administration. These mice are expected to be useful tools for analyzing the mechanisms of notochord development. Copyright © 2013 Wiley Periodicals, Inc.

  9. Strategic Planning for Chronic Disease Prevention in Rural America: Looking Through a PRISM Lens.

    PubMed

    Honeycutt, Amanda A; Wile, Kristina; Dove, Cassandra; Hawkins, Jackie; Orenstein, Diane

    2015-01-01

    Community-level strategic planning for chronic disease prevention. To share the outcomes of the strategic planning process used by Mississippi Delta stakeholders to prevent and reduce the negative impacts of chronic disease in their communities. A key component of strategic planning was participants' use of the Prevention Impacts Simulation Model (PRISM) to project the reduction, compared with the status quo, in deaths and costs from implementing interventions in Mississippi Delta communities. Participants in Mississippi Delta strategic planning meetings used PRISM, a user-friendly, evidence-based simulation tool that includes 22 categories of policy, systems, and environmental change interventions, to pose what-if questions that explore the likely short- and long-term effects of an intervention or any desired combination of the 22 categories of chronic disease intervention programs and policies captured in PRISM. These categories address smoking, air pollution, poor nutrition, and lack of physical activity. Strategic planning participants used PRISM outputs to inform their decisions and actions to implement interventions. Rural communities in the Mississippi Delta. A diverse group of 29 to 34 local chronic disease prevention stakeholders, known as the Mississippi Delta Strategic Alliance. Community plans and actions that were developed and implemented as a result of local strategic planning. Existing strategic planning efforts were complemented by the use of PRISM. The Mississippi Delta Strategic Alliance decided to implement new interventions to improve air quality and transportation and to expand existing interventions to reduce tobacco use and increase access to healthy foods. They also collaborated with the Department of Transportation to raise awareness and use of the current transportation network. The Mississippi Delta Strategic Alliance strategic planning process was complemented by the use of PRISM as a tool for strategic planning, which led to the

  10. Mutants of Cre recombinase with improved accuracy

    PubMed Central

    Eroshenko, Nikolai; Church, George M.

    2013-01-01

    Despite rapid advances in genome engineering technologies, inserting genes into precise locations in the human genome remains an outstanding problem. It has been suggested that site-specific recombinases can be adapted towards use as transgene delivery vectors. The specificity of recombinases can be altered either with directed evolution or via fusions to modular DNA-binding domains. Unfortunately, both wildtype and altered variants often have detectable activities at off-target sites. Here we use bacterial selections to identify mutations in the dimerization surface of Cre recombinase (R32V, R32M, and 303GVSdup) that improve the accuracy of recombination. The mutants are functional in bacteria, in human cells, and in vitro (except for 303GVSdup, which we did not purify), and have improved selectivity against both model off-target sites and the entire E. coli genome. We propose that destabilizing binding cooperativity may be a general strategy for improving the accuracy of dimeric DNA-binding proteins. PMID:24056590

  11. Thrust and parry of the SIOP (single integrated operational plan) and sdi (strategic defense initiative). Research report

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

    Zank, G.D.

    1989-05-01

    The relationship between strategic offensive capabilities (reflected in the SIOP) and emerging strategic defensive capabilities (reflected by SDI) is not being adequately addressed. A summary of the existing nuclear war planning process is provided, and an analagous defensive process is postulated. Parallels and differences between the two processes are discussed. Potential areas for information exchange and cooperation are identified to enhance deterrence and improve war fighting potential. Operational, technical and political issues requiring resolution are raised and recommendations to resolve these issues are made.

  12. Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle.

    PubMed

    Collins, Christine R; Das, Sujaan; Wong, Eleanor H; Andenmatten, Nicole; Stallmach, Robert; Hackett, Fiona; Herman, Jean-Paul; Müller, Sylke; Meissner, Markus; Blackman, Michael J

    2013-05-01

    Asexual blood stages of the malaria parasite, which cause all the pathology associated with malaria, can readily be genetically modified by homologous recombination, enabling the functional study of parasite genes that are not essential in this part of the life cycle. However, no widely applicable method for conditional mutagenesis of essential asexual blood-stage malarial genes is available, hindering their functional analysis. We report the application of the DiCre conditional recombinase system to Plasmodium falciparum, the causative agent of the most dangerous form of malaria. We show that DiCre can be used to obtain rapid, highly regulated site-specific recombination in P. falciparum, capable of excising loxP-flanked sequences from a genomic locus with close to 100% efficiency within the time-span of a single erythrocytic growth cycle. DiCre-mediated deletion of the SERA5 3' UTR failed to reduce expression of the gene due to the existence of alternative cryptic polyadenylation sites within the modified locus. However, we successfully used the system to recycle the most widely used drug resistance marker for P. falciparum, human dihydrofolate reductase, in the process producing constitutively DiCre-expressing P. falciparum clones that have broad utility for the functional analysis of essential asexual blood-stage parasite genes. © 2013 John Wiley & Sons Ltd.

  13. Strategic Planning: What's so Strategic about It?

    ERIC Educational Resources Information Center

    Strong, Bart

    2005-01-01

    The words "strategic" and "planning" used together can lead to confusion unless one spent the early years of his career in never-ending, team-oriented, corporate training sessions. Doesn't "strategic" have something to do with extremely accurate bombing or a defensive missile system or Star Wars or something? Don't "strategic" and "planning" both…

  14. The need for strategic tax planning among nonprofit hospitals.

    PubMed

    Smith, Pamela C

    2005-01-01

    Strategic tax planning issues are important to the nonprofit health care sector, despite its philanthropic mission. The consolidation of the industry has led management to fight for resources and develop alternative strategies for raising money. When management evaluates alternative collaborative structures to increase efficiency, the impact on governance structures must also be considered. The increased governmental scrutiny of joint ventures within the health care sector warrants management's attention as well. The financial incentives must be considered, along with the various tax policy implications of cross-sector collaborations.

  15. Critical Religious Education (CRE) in Practice: Evaluating the Reception of an Introductory Scheme of Work

    ERIC Educational Resources Information Center

    Goodman, Angela

    2018-01-01

    Critical Religious Education (CRE) is a contemporary pedagogy of religious education developed by Andrew Wright and various colleagues over the past two decades. There has been widespread academic discourse about the pedagogy in theory but increasingly commentators have called for examples of it in practice. Over the past seven years a writing…

  16. Strategic Analysis Overview

    NASA Technical Reports Server (NTRS)

    Cirillo, William M.; Earle, Kevin D.; Goodliff, Kandyce E.; Reeves, J. D.; Stromgren, Chel; Andraschko, Mark R.; Merrill, R. Gabe

    2008-01-01

    NASA s Constellation Program employs a strategic analysis methodology in providing an integrated analysis capability of Lunar exploration scenarios and to support strategic decision-making regarding those scenarios. The strategic analysis methodology integrates the assessment of the major contributors to strategic objective satisfaction performance, affordability, and risk and captures the linkages and feedbacks between all three components. Strategic analysis supports strategic decision making by senior management through comparable analysis of alternative strategies, provision of a consistent set of high level value metrics, and the enabling of cost-benefit analysis. The tools developed to implement the strategic analysis methodology are not element design and sizing tools. Rather, these models evaluate strategic performance using predefined elements, imported into a library from expert-driven design/sizing tools or expert analysis. Specific components of the strategic analysis tool set include scenario definition, requirements generation, mission manifesting, scenario lifecycle costing, crew time analysis, objective satisfaction benefit, risk analysis, and probabilistic evaluation. Results from all components of strategic analysis are evaluated a set of pre-defined figures of merit (FOMs). These FOMs capture the high-level strategic characteristics of all scenarios and facilitate direct comparison of options. The strategic analysis methodology that is described in this paper has previously been applied to the Space Shuttle and International Space Station Programs and is now being used to support the development of the baseline Constellation Program lunar architecture. This paper will present an overview of the strategic analysis methodology and will present sample results from the application of the strategic analysis methodology to the Constellation Program lunar architecture.

  17. 50 CFR 14.23 - Live farm-raised fish and farm-raised fish eggs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 1 2013-10-01 2013-10-01 false Live farm-raised fish and farm-raised fish eggs. 14.23 Section 14.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... Exportation at Designated Ports § 14.23 Live farm-raised fish and farm-raised fish eggs. Live farm-raised fish...

  18. 50 CFR 14.23 - Live farm-raised fish and farm-raised fish eggs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 1 2014-10-01 2014-10-01 false Live farm-raised fish and farm-raised fish eggs. 14.23 Section 14.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... Exportation at Designated Ports § 14.23 Live farm-raised fish and farm-raised fish eggs. Live farm-raised fish...

  19. 50 CFR 14.23 - Live farm-raised fish and farm-raised fish eggs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 1 2012-10-01 2012-10-01 false Live farm-raised fish and farm-raised fish eggs. 14.23 Section 14.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... Exportation at Designated Ports § 14.23 Live farm-raised fish and farm-raised fish eggs. Live farm-raised fish...

  20. Gene Expression Profiling with Cre-Conditional Pseudorabies Virus Reveals a Subset of Midbrain Neurons That Participate in Reward Circuitry

    PubMed Central

    Pomeranz, Lisa E.; Ekstrand, Mats I.; Latcha, Kaamashri N.; Smith, Gregory A.; Enquist, Lynn W.

    2017-01-01

    The mesolimbic dopamine pathway receives inputs from numerous regions of the brain as part of a neural system that detects rewarding stimuli and coordinates a behavioral response. The capacity to simultaneously map and molecularly define the components of this complex multisynaptic circuit would thus advance our understanding of the determinants of motivated behavior. To accomplish this, we have constructed pseudorabies virus (PRV) strains in which viral propagation and fluorophore expression are activated only after exposure to Cre recombinase. Once activated in Cre-expressing neurons, the virus serially labels chains of presynaptic neurons. Dual injection of GFP and mCherry tracing viruses simultaneously illuminates nigrostriatal and mesolimbic circuitry and shows no overlap, demonstrating that PRV transmission is confined to synaptically connected neurons. To molecularly profile mesolimbic dopamine neurons and their presynaptic inputs, we injected Cre-conditional GFP virus into the NAc of (anti-GFP) nanobody-L10 transgenic mice and immunoprecipitated translating ribosomes from neurons infected after retrograde tracing. Analysis of purified RNA revealed an enrichment of transcripts expressed in neurons of the dorsal raphe nuclei and lateral hypothalamus that project to the mesolimbic dopamine circuit. These studies identify important inputs to the mesolimbic dopamine pathway and further show that PRV circuit-directed translating ribosome affinity purification can be broadly applied to identify molecularly defined neurons comprising complex, multisynaptic circuits. SIGNIFICANCE STATEMENT The mesolimbic dopamine circuit integrates signals from key brain regions to detect and respond to rewarding stimuli. To further define this complex multisynaptic circuit, we constructed a panel of Cre recombinase-activated pseudorabies viruses (PRVs) that enabled retrograde tracing of neural inputs that terminate on Cre-expressing neurons. Using these viruses and Retro

  1. Neurocognitive dysfunction in strategic and non-strategic gamblers.

    PubMed

    Grant, Jon E; Odlaug, Brian L; Chamberlain, Samuel R; Schreiber, Liana R N

    2012-08-07

    It has been theorized that there may be subtypes of pathological gambling, particularly in relation to the main type of gambling activities undertaken. Whether or not putative pathological gambling subtypes differ in terms of their clinical and cognitive profiles has received little attention. Subjects meeting DSM-IV criteria for pathological gambling were grouped into two categories of preferred forms of gambling - strategic (e.g., cards, dice, sports betting, stock market) and non-strategic (e.g., slots, video poker, pull tabs). Groups were compared on clinical characteristics (gambling severity, and time and money spent gambling), psychiatric comorbidity, and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Seventy-seven subjects were included in this sample (45.5% females; mean age: 42.7±14.9) which consisted of the following groups: strategic (n=22; 28.6%) and non-strategic (n=55; 71.4%). Non-strategic gamblers were significantly more likely to be older, female, and divorced. Money spent gambling did not differ significantly between groups although one measure of gambling severity reflected more severe problems for strategic gamblers. Strategic and non-strategic gamblers did not differ in terms of cognitive function; both groups showed impairments in cognitive flexibility and inhibitory control relative to matched healthy volunteers. These preliminary results suggest that preferred form of gambling may be associated with specific clinical characteristics but are not dissociable in terms of cognitive inflexibility and motor impulsivity. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Raising Awareness in Science Education for Women (RAISE-W)

    NASA Astrophysics Data System (ADS)

    Faherty, Jacqueline K.; Holford, M.

    2014-01-01

    Raising Awareness in Science Education for Women (RAISE-W) is a 501c non profit corporation whose mission is to aid in increasing and retaining the number of women - especially underrepresented females - engaged in scientific teaching and research. Initiated by a Protein Chemist and an Astronomer, our ultimate goal has been to develop informational tools and create innovative outreach programs for women across all STEM fields. At present RAISE-W is recruiting women at the undergraduate, graduate, and early career stages to participate in a unique, 1-year, executive coaching program modeled after those used in the business sector.

  3. Establishment of a Cre recombinase based mutagenesis protocol for markerless gene deletion in Streptococcus suis.

    PubMed

    Koczula, A; Willenborg, J; Bertram, R; Takamatsu, D; Valentin-Weigand, P; Goethe, R

    2014-12-01

    The lack of knowledge about pathogenicity mechanisms of Streptococcus (S.) suis is, at least partially, attributed to limited methods for its genetic manipulation. Here, we established a Cre-lox based recombination system for markerless gene deletions in S. suis serotype 2 with high selective pressure and without undesired side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Strategic Leadership

    ERIC Educational Resources Information Center

    Davies, Barbara; Davies, Brent

    2004-01-01

    This article explores the nature of strategic leadership and assesses whether a framework can be established to map the dimensions of strategic leadership. In particular it establishes a model which outlines both the organizational abilities and the individual characteristics of strategic leaders.

  5. Can Strategic Ignorance Explain the Evolution of Love?

    PubMed

    Bear, Adam; Rand, David G

    2018-04-24

    People's devotion to, and love for, their romantic partners poses an evolutionary puzzle: Why is it better to stop your search for other partners once you enter a serious relationship when you could continue to search for somebody better? A recent formal model based on "strategic ignorance" suggests that such behavior can be adaptive and favored by natural selection, so long as you can signal your unwillingness to "look" for other potential mates to your current partner. Here, we re-examine this conclusion with a more detailed model designed to capture specific features of romantic relationships. We find, surprisingly, that devotion does not typically evolve in our model: Selection favors agents who choose to "look" while in relationships and who allow their partners to do the same. Non-looking is only expected to evolve if there is an extremely large cost associated with being left by your partner. Our results therefore raise questions about the role of strategic ignorance in explaining the evolution of love. Copyright © 2018 Cognitive Science Society, Inc.

  6. Between a Rock and a Hard Place: Raising Rates To Raise Wages. A How-To Book on Raising Rates.

    ERIC Educational Resources Information Center

    Boyer, Margaret, Ed.; And Others

    The Child Care Workers Alliance takes the position that child care professionals have the right to raise rates to a level at which they can make a living wage without feeling guilty. This booklet provides ideas and strategies for raising rates. Introductory materials provide background information, steps to raising rates, and a rationale for…

  7. Strategic Budgeting.

    ERIC Educational Resources Information Center

    Jones, Dennis P.

    1993-01-01

    An approach to college budgeting that encompasses strategic as well as operational decisions is proposed. Strategic decisions focus on creation and maintenance of institutional capacity, whereas operational decisions focus on use of that capacity to accomplish specific purposes. Strategic budgeting must emphasize institutional assets and their…

  8. Structure, environment and strategic outcome: a study of Pennsylvania nursing homes.

    PubMed

    Aaronson, W E; Zinn, J S; Rosko, M D

    1995-02-01

    This study applies Porter's model of competitive advantage to the nursing home industry. Discriminant analysis is used to identify organizational and environmental characteristics associated with nursing homes which have demonstrated valued strategic outcomes, and to distinguish the more successful nursing homes from their rivals. The results of the discriminant analysis suggest that nursing homes with superior payer mix outcomes are distinguishable from their less successful rivals in areas associated with a focused generic strategy. The study suggests that nursing homes which are better staffed, of smaller size and lower price are more likely to achieve high levels of self-pay utilization. Independent living units, continuing care retirement communities in particular, are likely to act synergistically with nursing home organizational characteristics to enhance competitive advantage by linking the value chain of the nursing home to that of retirement housing. Nursing homes with higher proportions of Medicare were found to provide a unique product when compared to their rivals. Profit status does not discriminate better self-pay strategic utilization, but for-profit facilities are more likely to pursue a Medicare strategy. Concern was raised that, as nursing homes become more strategically oriented, Medicaid access may become more problematic.

  9. Neural signatures of strategic types in a two-person bargaining game

    PubMed Central

    Bhatt, Meghana A.; Lohrenz, Terry; Camerer, Colin F.; Montague, P. Read

    2010-01-01

    The management and manipulation of our own social image in the minds of others requires difficult and poorly understood computations. One computation useful in social image management is strategic deception: our ability and willingness to manipulate other people's beliefs about ourselves for gain. We used an interpersonal bargaining game to probe the capacity of players to manage their partner's beliefs about them. This probe parsed the group of subjects into three behavioral types according to their revealed level of strategic deception; these types were also distinguished by neural data measured during the game. The most deceptive subjects emitted behavioral signals that mimicked a more benign behavioral type, and their brains showed differential activation in right dorsolateral prefrontal cortex and left Brodmann area 10 at the time of this deception. In addition, strategic types showed a significant correlation between activation in the right temporoparietal junction and expected payoff that was absent in the other groups. The neurobehavioral types identified by the game raise the possibility of identifying quantitative biomarkers for the capacity to manipulate and maintain a social image in another person's mind. PMID:21041646

  10. Nucleo-cytoplasmic shuttling dynamics of the transcriptional regulators XYR1 and CRE1 under conditions of cellulase and xylanase gene expression in Trichoderma reesei

    PubMed Central

    Lichius, Alexander; Seidl-Seiboth, Verena; Seiboth, Bernhard; Kubicek, Christian P

    2014-01-01

    Trichoderma reesei is a model for investigating the regulation of (hemi-)cellulase gene expression. Cellulases are formed adaptively, and the transcriptional activator XYR1 and the carbon catabolite repressor CRE1 are main regulators of their expression. We quantified the nucleo-cytoplasmic shuttling dynamics of GFP-fusion proteins of both transcription factors under cellulase and xylanase inducing conditions, and correlated their nuclear presence/absence with transcriptional changes. We also compared their subcellular localization in conidial germlings and mature hyphae. We show that cellulase gene expression requires de novo biosynthesis of XYR1 and its simultaneous nuclear import, whereas carbon catabolite repression is regulated through preformed CRE1 imported from the cytoplasmic pool. Termination of induction immediately stopped cellulase gene transcription and was accompanied by rapid nuclear degradation of XYR1. In contrast, nuclear CRE1 rapidly decreased upon glucose depletion, and became recycled into the cytoplasm. In mature hyphae, nuclei containing activated XYR1 were concentrated in the colony center, indicating that this is the main region of XYR1 synthesis and cellulase transcription. CRE1 was found to be evenly distributed throughout the entire mycelium. Taken together, our data revealed novel aspects of the dynamic shuttling and spatial bias of the major regulator of (hemi-)cellulase gene expression, XYR1, in T. reesei. PMID:25302561

  11. Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice

    PubMed Central

    Zariwala, Hatim A.; Madisen, Linda; Ahrens, Kurt F.; Bernard, Amy; Lein, Edward S.; Jones, Allan R.; Zeng, Hongkui

    2011-01-01

    The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two-photon calcium dye imaging: Wfs1(+)/Gad1(−) mice that labels layer 2/3 excitatory cell population and Pvalb(+)/Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e., high selectivity and tuning to the angle, direction, and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow-spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional, and connectivity studies. PMID:21283555

  12. 50 CFR 14.23 - Live farm-raised fish and farm-raised fish eggs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... eggs. 14.23 Section 14.23 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... Exportation at Designated Ports § 14.23 Live farm-raised fish and farm-raised fish eggs. Live farm-raised fish and farm-raised fish eggs meet the definition of “bred in captivity” as stated in 50 CFR 17.3. Except...

  13. 75 FR 67695 - U.S. Strategic Command Strategic Advisory Group Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary of Defense U.S. Strategic Command Strategic Advisory... meeting notice of the U.S. Strategic Command Strategic Advisory Group. DATES: December 9, 2010: 8 a.m. to..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

  14. Application of the Cre/loxP Site-Specific Recombination System for Gene Transformation in Aurantiochytrium limacinum.

    PubMed

    Sun, Hengyi; Chen, Hao; Zang, Xiaonan; Hou, Pan; Zhou, Bingbing; Liu, Yuantao; Wu, Fei; Cao, Xiaofei; Zhang, Xuecheng

    2015-06-01

    The Cre/loxP site-specific recombination system was applied to Aurantiochytrium limacinum to obtain a transformant without the antibiotic resistance marker gene. First, the enhanced green fluorescent protein gene (egfp) and chloramphenicol resistance gene (Cmr), along with the two loxP loci, were integrated into the genome of A. limacinum OUC88 using 18S rDNA sequences as the homologous recombination sites. Then plasmid pSH65, containing a zeocin resistance gene (Bler) was transferred into A. limacinum OUC_CG. After induction with galactose, repeated passage in culture and PCR-based assessment, the pSH65 plasmid was lost and A. limacinum OUC_EG host was shown to no longer have resistance to 100 mg chloramphenicol/L or 5 mg zeocin/L. Through southern blotting and fluorescence detection, egfp was found to be integrated into the genome of A. limacinum OUC_EG, and EGFP was successfully expressed in the cells. The successful application of the Cre/loxP system demonstrates an experimental basis for genetic modification of A. limacinum so as to obtain transformed strains with no antibiotic resistance marker genes.

  15. Development of Cre-loxP technology in zebrafish to study the regulation of fish reproduction.

    PubMed

    Lin, Heng-Ju; Lee, Shu-Hua; Wu, Jen-Leih; Duann, Yeh-Fang; Chen, Jyh-Yih

    2013-12-01

    One cannot seek permission to market transgenic fish mainly because there is no field test or any basic research on technological developments for evaluating their biosafety. Infertility is a necessary adjunct to exploiting transgenic fish unless completely secure land-locked facilities are available. In this study, we report the generation of a Cre transgenic zebrafish line using a cytomegalovirus promoter. We also produced fish carrying the Bax1 and Bax2 plasmids; these genes were separated by two loxP sites under a zona pellucida C promoter or were driven by an anti-Müllerian hormone promoter. We inserted a red fluorescent protein gene between the two loxP sites. After obtaining transgenic lines with the two transgenic fish crossed with each other (Cre transgenic zebrafish x loxP transgenic zebrafish), the floxed DNA was found to be specifically eliminated from the female or male zebrafish, and apoptosis gene expressions caused ovarian and testicular growth cessation and degeneration. Overexpression of the Bax1 and Bax2 genes caused various expression levels of apoptosis-related genes. Accordingly, this transgenic zebrafish model system provides a method to produce infertile fish and may be useful for application to genetically modified fish.

  16. Strategic financial analysis: the CFO's role in strategic planning.

    PubMed

    Litos, D M

    1985-03-01

    Strategic financial analysis, the financial information support system for the strategic planning process, provides information vital to maintaining a healthy bottom line. This article, the third in HCSM's series on the organizational components of strategic planning, reviews the role of the chief financial officer in determining which programs and services will best meet the future needs of the institution.

  17. Dysregulation of Uterine Signaling Pathways in Progesterone Receptor-Cre Knockout of Dicer

    PubMed Central

    Andreu-Vieyra, Claudia V.; Kim, Tae Hoon; Jeong, Jae-Wook; Hodgson, Myles C.; Chen, Ruihong; Creighton, Chad J.; Lydon, John P.; Gunaratne, Preethi H.; DeMayo, Francesco J.; Matzuk, Martin M.

    2012-01-01

    Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNA (miRNA) have been implicated in several reproductive processes, the specific roles of Dicer and miRNA in uterine development are not known. To address the roles of miRNA in the regulation of key uterine pathways, we generated a conditional knockout of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor-Cre. These Dicer conditional knockout females are sterile with small uteri, which demonstrate significant defects, including absence of glandular epithelium and enhanced stromal apoptosis, beginning at approximately postnatal d 15, with coincident expression of Cre and deletion of Dicer. Specific miRNA (miR-181c, −200b, −101, let-7d) were down-regulated and corresponding predicted proapoptotic target genes (Bcl2l11, Aldh1a3) were up-regulated, reflecting the apoptotic phenomenon. Although these mice had normal serum hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/β-catenin canonical pathway, were dysregulated at the mRNA level. Importantly, uterine stromal cell proliferation in response to progesterone was absent, whereas uterine epithelial cell proliferation in response to estradiol was maintained in adult uteri. These data implicate Dicer and appropriate miRNA expression as essential players in the regulation of multiple uterine signaling pathways required for uterine development and appropriate function. PMID:22798293

  18. Being a Learner Using Social Media in School: The Case of Space2cre8

    ERIC Educational Resources Information Center

    Vasbø, Kristin Beate; Silseth, Kenneth; Erstad, Ola

    2014-01-01

    The aim of this article is to gain knowledge about what it means to be a learner using social media in an educational setting. The article presents an ethnographic study of students in a multiethnic community in Oslo who participate in a social networking site called Space2cre8 (S28). In this article, we set out to explore the kind of space for…

  19. Mesoporous Silica Nanoparticle-Mediated Intracellular Cre Protein Delivery for Maize Genome Editing via loxP Site Excision1,2[W][OPEN

    PubMed Central

    Martin-Ortigosa, Susana; Peterson, David J.; Valenstein, Justin S.; Lin, Victor S.-Y.; Trewyn, Brian G.; Lyznik, L. Alexander; Wang, Kan

    2014-01-01

    The delivery of proteins instead of DNA into plant cells allows for a transient presence of the protein or enzyme that can be useful for biochemical analysis or genome modifications. This may be of particular interest for genome editing, because it can avoid DNA (transgene) integration into the genome and generate precisely modified “nontransgenic” plants. In this work, we explore direct protein delivery to plant cells using mesoporous silica nanoparticles (MSNs) as carriers to deliver Cre recombinase protein into maize (Zea mays) cells. Cre protein was loaded inside the pores of gold-plated MSNs, and these particles were delivered by the biolistic method to plant cells harboring loxP sites flanking a selection gene and a reporter gene. Cre protein was released inside the cell, leading to recombination of the loxP sites and elimination of both genes. Visual selection was used to select recombination events from which fertile plants were regenerated. Up to 20% of bombarded embryos produced calli with the recombined loxP sites under our experimental conditions. This direct and reproducible technology offers an alternative for DNA-free genome-editing technologies in which MSNs can be tailored to accommodate the desired enzyme and to reach the desired tissue through the biolistic method. PMID:24376280

  20. Using electronic patient records to inform strategic decision making in primary care.

    PubMed

    Mitchell, Elizabeth; Sullivan, Frank; Watt, Graham; Grimshaw, Jeremy M; Donnan, Peter T

    2004-01-01

    Although absolute risk of death associated with raised blood pressure increases with age, the benefits of treatment are greater in elderly patients. Despite this, the 'rule of halves' particularly applies to this group. We conducted a randomised controlled trial to evaluate different levels of feedback designed to improve identification, treatment and control of elderly hypertensives. Fifty-two general practices were randomly allocated to either: Control (n=19), Audit only feedback (n=16) or Audit plus Strategic feedback, prioritising patients by absolute risk (n=17). Feedback was based on electronic data, annually extracted from practice computer systems. Data were collected for 265,572 patients, 30,345 aged 65-79. The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced. There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group. Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control.

  1. Raising Confident Kids

    MedlinePlus

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body ... Videos for Educators Search English Español Raising Confident Kids KidsHealth / For Parents / Raising Confident Kids What's in ...

  2. A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus.

    PubMed

    Liang, Xun; Sun, Leqiang; Yu, Teng; Pan, Yongfei; Wang, Dongdong; Hu, Xueying; Fu, Zhenfang; He, Qigai; Cao, Gang

    2016-01-18

    Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate's protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.

  3. A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus

    PubMed Central

    Liang, Xun; Sun, Leqiang; Yu, Teng; Pan, Yongfei; Wang, Dongdong; Hu, Xueying; Fu, Zhenfang; He, Qigai; Cao, Gang

    2016-01-01

    Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development. PMID:26777545

  4. Strategic Plan. Volume 2

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Mission of the NSBRI will be to lead a National effort for accomplishing the integrated, critical path, biomedical research necessary to support the long term human presence, development, and exploration of space and to enhance life on Earth by applying the resultant advances in human knowledge and technology acquired through living and working in space. To carry out this mission, the NSBRI focuses its activities on three Strategic Programs: Strategic Program 1: Countermeasure Research Strategic Program 2: Education, Training and Outreach Strategic Program 3: Cooperative Research and Development. This document contains the detailed Team Strategic Plans for the 11 research teams focused on Strategic Program 1, and the Education and Outreach Team focused on Strategic Program 2. There is overlap and integration among the Programs and Team Strategic Plans, as described in each of the Plans.

  5. 11. Strategic planning.

    PubMed

    2014-05-01

    There are several types of planning processes and plans, including strategic, operational, tactical, and contingency. For this document, operational planning includes tactical planning. This chapter examines the strategic planning process and includes an introduction into disaster response plans. "A strategic plan is an outline of steps designed with the goals of the entire organisation as a whole in mind, rather than with the goals of specific divisions or departments". Strategic planning includes all measures taken to provide a broad picture of what must be achieved and in which order, including how to organise a system capable of achieving the overall goals. Strategic planning often is done pre-event, based on previous experience and expertise. The strategic planning for disasters converts needs into a strategic plan of action. Strategic plans detail the goals that must be achieved. The process of converting needs into plans has been deconstructed into its components and includes consideration of: (1) disaster response plans; (2) interventions underway or planned; (3) available resources; (4) current status vs. pre-event status; (5) history and experience of the planners; and (6) access to the affected population. These factors are tempered by the local: (a) geography; (b) climate; (c) culture; (d) safety; and (e) practicality. The planning process consumes resources (costs). All plans must be adapted to the actual conditions--things never happen exactly as planned.

  6. The Strategic Attitude: Integrating Strategic Planning into Daily University Worklife

    ERIC Educational Resources Information Center

    Dickmeyer, Nathan

    2004-01-01

    Chief financial officers in today's universities are so busy with the challenges of day-to-day management that strategic thinking often takes a back seat. Planning for strategic change can go a long way toward streamlining the very daily tasks that obscure the "big picture." Learning how to integrate strategic thinking into day-to-day management…

  7. Update: Fund Raising.

    ERIC Educational Resources Information Center

    Change, 1979

    1979-01-01

    A wide range of approaches to fund raising in higher education institutions is reported. The nine references cover such topics as: coping with reduced resources in community colleges, administering charitable remainder trusts, annuity plans, capital fund drives, fund raising in public colleges, endowment earnings, foundations, and alumni support.…

  8. Raising the standards of the calf-raise test: a systematic review.

    PubMed

    Hébert-Losier, Kim; Newsham-West, Richard J; Schneiders, Anthony G; Sullivan, S John

    2009-11-01

    The calf-raise test is used by clinicians and researchers in sports medicine to assess properties of the calf muscle-tendon unit. The test generally involves repetitive concentric-eccentric muscle action of the plantar-flexors in unipedal stance and is quantified by the number of raises performed. Although the calf-raise test appears to have acceptable reliability and face validity, and is commonly used for medical assessment and rehabilitation of injuries, no universally acceptable test parameters have been published to date. A systematic review of the existing literature was conducted to investigate the consistency as well as universal acceptance of the evaluation purposes, test parameters, outcome measurements and psychometric properties of the calf-raise test. Nine electronic databases were searched during the period May 30th to September 21st 2008. Forty-nine articles met the inclusion criteria and were quality assessed. Information on study characteristics and calf-raise test parameters, as well as quantitative data, were extracted; tabulated; and statistically analysed. The average quality score of the reviewed articles was 70.4+/-12.2% (range 44-90%). Articles provided various test parameters; however, a consensus was not ascertained. Key testing parameters varied, were often unstated, and few studies reported reliability or validity values, including sensitivity and specificity. No definitive normative values could be established and the utility of the test in subjects with pathologies remained unclear. Although adapted for use in several disciplines and traditionally recommended for clinical assessment, there is no uniform description of the calf-raise test in the literature. Further investigation is recommended to ensure consistent use and interpretation of the test by researchers and clinicians.

  9. Strategic Leadership Reconsidered

    ERIC Educational Resources Information Center

    Davies, Brent; Davies, Barbara J.

    2005-01-01

    This paper will address the challenge of how strategic leadership can be defined and articulated to provide a framework for developing a strategically focused school drawing on a NCSL research project. The paper is structured into three main parts. Part one outlines the elements that comprise a strategically focused school, develops an…

  10. Strategic Control Algorithm Development : Volume 3. Strategic Algorithm Report.

    DOT National Transportation Integrated Search

    1974-08-01

    The strategic algorithm report presents a detailed description of the functional basic strategic control arrival algorithm. This description is independent of a particular computer or language. Contained in this discussion are the geometrical and env...

  11. Strategic groups, performance, and strategic response in the nursing home industry.

    PubMed

    Zinn, J S; Aaronson, W E; Rosko, M D

    1994-06-01

    This study examines the effect of strategic group membership on nursing home performance and strategic behavior. Data from the 1987 Medicare and Medicaid Automated Certification Survey were combined with data from the 1987 and 1989 Pennsylvania Long Term Care Facility Questionnaire. The sample consisted of 383 Pennsylvania nursing homes. Cluster analysis was used to place the 383 nursing homes into strategic groups on the basis of variables measuring scope and resource deployment. Performance was measured by indicators of the quality of nursing home care (rates of pressure ulcers, catheterization, and restraint usage) and efficiency in services provision. Changes in Medicare participation after passage of the 1988 Medicare Catastrophic Coverage Act (MCCA) measured strategic behavior. MANOVA and Turkey HSD post hoc means tests determined if significant differences were associated with strategic group membership. Cluster analysis produced an optimal seven-group solution. Differences in group means were significant for the clustering, performance, and conduct variables (p < .0001). Strategic groups characterized by facilities providing a continuum of care services had the best patient care outcomes. The most efficient groups were characterized by facilities with high Medicare census. While all strategic groups increased Medicare census following passage of the MCCA, those dominated by for-profits had the greatest increases. Our analysis demonstrates that strategic orientation influences nursing home response to regulatory initiatives, a factor that should be recognized in policy formation directed at nursing home reform.

  12. Strategic groups, performance, and strategic response in the nursing home industry.

    PubMed Central

    Zinn, J S; Aaronson, W E; Rosko, M D

    1994-01-01

    OBJECTIVE. This study examines the effect of strategic group membership on nursing home performance and strategic behavior. DATA SOURCES AND STUDY SETTING. Data from the 1987 Medicare and Medicaid Automated Certification Survey were combined with data from the 1987 and 1989 Pennsylvania Long Term Care Facility Questionnaire. The sample consisted of 383 Pennsylvania nursing homes. STUDY DESIGN. Cluster analysis was used to place the 383 nursing homes into strategic groups on the basis of variables measuring scope and resource deployment. Performance was measured by indicators of the quality of nursing home care (rates of pressure ulcers, catheterization, and restraint usage) and efficiency in services provision. Changes in Medicare participation after passage of the 1988 Medicare Catastrophic Coverage Act (MCCA) measured strategic behavior. MANOVA and Turkey HSD post hoc means tests determined if significant differences were associated with strategic group membership. FINDINGS. Cluster analysis produced an optimal seven-group solution. Differences in group means were significant for the clustering, performance, and conduct variables (p < .0001). Strategic groups characterized by facilities providing a continuum of care services had the best patient care outcomes. The most efficient groups were characterized by facilities with high Medicare census. While all strategic groups increased Medicare census following passage of the MCCA, those dominated by for-profits had the greatest increases. CONCLUSIONS. Our analysis demonstrates that strategic orientation influences nursing home response to regulatory initiatives, a factor that should be recognized in policy formation directed at nursing home reform. PMID:8005789

  13. NASA Strategic Plan

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The aforementioned strategic decisions and the overarching direction for America's aeronautics and space program are addressed in the Strategic Plan. Our Strategic Plan is critical to our ability to meet the challenges of this new era and deliver a vibrant aeronautics and space program that strengthens and inspires the Nation. The Plan is our top-level strategy.

  14. 78 FR 67131 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    .... Strategic Command Strategic Advisory Group AGENCY: Department of Defense. ACTION: Notice of Advisory... following Federal Advisory Committee meeting of the U.S. Strategic Command Strategic Advisory Group. DATES... issues to the Commander, U.S. Strategic Command, during the development of the Nation's strategic war...

  15. 77 FR 54615 - Strategic Management Program; Fiscal Year 2013-2016 Strategic Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... Manager, Strategic Management Program; National Transportation Safety Board, 490 L'Enfant Plaza SW., MD-1... NATIONAL TRANSPORTATION SAFETY BOARD Strategic Management Program; Fiscal Year 2013-2016 Strategic Plan AGENCY: National Transportation Safety Board. ACTION: Notice: Request for comments. SUMMARY: This...

  16. 75 FR 18824 - Federal Advisory Committee; U.S. Strategic Command Strategic Advisory Group; Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... DEPARTMENT OF DEFENSE Office of the Secretary Federal Advisory Committee; U.S. Strategic Command... 102-3.150, the Department of Defense announces that the U.S. Strategic Command Strategic Advisory... Commander, U.S. Strategic Command, during the development of the Nation's strategic war plans. Agenda Topics...

  17. Figla-Cre Transgenic Mice Expressing Myristoylated EGFP in Germ Cells Provide a Model for Investigating Perinatal Oocyte Dynamics

    PubMed Central

    Lin, Ruei-Shiuan; Jimenez-Movilla, Maria; Dean, Jurrien

    2014-01-01

    FIGLA (Factor in the germline, alpha) is a bHLH transcription factor expressed abundantly in female and less so in male germ cells. Mice lacking FIGLA do not form primordial follicles in the ovary and females are sterile, but there is no obvious phenotype in males. Using the Figla promoter to express Cre recombinase, we have established mEGFP/mTomato reporter mice with green germ cells and red somatic tissue. These mice were crossed into the Figla null background to accelerate perinatal oocyte loss. Live imaging of cultured newborn ovaries provides evidence that few oocytes egress and the vast majority disappear within the confines of the ovary. Although a cohort of mobile, phagocytic cells was observed, macrophage depletion in Csf1op/op mice did not affect oocyte loss. Investigations with TUNEL assays and caspase inhibitors suggest that apoptosis plays a role in the perinatal loss of oocyte in female mice. These results establish the utility of Figla-EGFP/Cre; mTomato/mEGFP in investigating germ cell dynamics in prepubertal mice. PMID:24400092

  18. Learning to think strategically.

    PubMed

    1994-01-01

    Strategic thinking focuses on issues that directly affect the ability of a family planning program to attract and retain clients. This issue of "The Family Planning Manager" outlines the five steps of strategic thinking in family planning administration: 1) define the organization's mission and strategic goals; 2) identify opportunities for improving quality, expanding access, and increasing demand; 3) evaluate each option in terms of its compatibility with the organization's goals; 4) select an option; and 5) transform strategies into action. Also included in this issue is a 20-question test designed to permit readers to assess their "strategic thinking quotient" and a list of sample questions to guide a strategic analysis.

  19. 76 FR 14950 - Closed Meeting of the U.S. Strategic Command Strategic Advisory Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... DEPARTMENT OF DEFENSE Office of the Secretary Closed Meeting of the U.S. Strategic Command.... Strategic Command Strategic Advisory Group. DATES: April 7, 2011, from 8 a.m. to 5 p.m. and April 8, 2011... policy-related issues to the Commander, U.S. Strategic Command, during the development of the Nation's...

  20. Processing of intended and unintended strategic issues and integration into the strategic agenda.

    PubMed

    Ridder, Hans-Gerd; Schrader, Jan Simon

    2017-11-01

    Strategic change is needed in hospitals due to external and internal pressures. However, research on strategic change, as a combination of management and medical expertise in hospitals, remains scarce. We analyze how intended strategic issues are processed into deliberate strategies and how unintended strategic issues are processed into emergent strategies in the management of strategy formation in hospitals. This study empirically investigates the integration of medical and management expertise in strategy formation. The longitudinal character of the case study enabled us to track patterns of intended and unintended strategic issues over 2 years. We triangulated data from interviews, observations, and documents. In accordance with the quality standards of qualitative research procedures, we analyzed the data by pattern matching and provided analytical generalization regarding strategy formation in hospitals. Our findings suggest that strategic issues are particularly successful within the strategy formation process if interest groups are concerned with the strategic issue, prospective profits are estimated, and relevant decisions makers are involved early on. Structure and interaction processes require clear criteria and transparent procedures for effective strategy formation. There is systematic neglect of medical expertise in processes of generating strategies. Our study reveals that the decentralized structure of medical centers is an adequate template for both the operationalization of intended strategic issues and the development of unintended strategic issues. However, tasks, roles, responsibility, resources, and administrative support are necessary for effective management of strategy formation. Similarly, criteria, procedures, and decision-making are prerequisites for effective strategy formation.

  1. 77 FR 61581 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    .... Strategic Command Strategic Advisory Group AGENCY: Department of Defense. ACTION: Notice of Advisory... advisory committee: U.S. Strategic Command Strategic Advisory Group. DATES: November 15, 2012, from 8 a.m... Command, during the development of the Nation's strategic war plans. Agenda: Topics include: Policy Issues...

  2. Strategic Planning for Independent Schools.

    ERIC Educational Resources Information Center

    Stone, Susan C.

    This manual is intended to serve independent schools beginning strategic planning methods. Chapter 1, "The Case for Strategic Planning," suggests replacing the term "long range planning" with the term "strategic planning," which emphasizes change. The strategic planning and policy development process begins with…

  3. A Tet-on and Cre-loxP Based Genetic Engineering System for Convenient Recycling of Selection Markers in Penicillium oxalicum

    PubMed Central

    Jiang, Baojie; Zhang, Ruiqin; Feng, Dan; Wang, Fangzhong; Liu, Kuimei; Jiang, Yi; Niu, Kangle; Yuan, Quanquan; Wang, Mingyu; Wang, Hailong; Zhang, Youming; Fang, Xu

    2016-01-01

    The lack of selective markers has been a key problem preventing multistep genetic engineering in filamentous fungi, particularly for industrial species such as the lignocellulose degrading Penicillium oxalicum JUA10-1(formerly named as Penicillium decumbens). To resolve this problem, we constructed a genetic manipulation system taking advantage of two established genetic systems: the Cre-loxP system and Tet-on system in P. oxalicum JUA10-1. This system is efficient and convenient. The expression of Cre recombinase was activated by doxycycline since it was controlled by Tet-on system. Using this system, two genes, ligD and bglI, were sequentially disrupted by loxP flanked ptrA. The successful application of this procedure will provide a useful tool for genetic engineering in filamentous fungi. This system will also play an important role in improving the productivity of interesting products and minimizing by-product when fermented by filamentous fungi. PMID:27148179

  4. Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

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

    Antonson, P., E-mail: per.antonson@ki.se; Omoto, Y.; Humire, P.

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established amore » new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.« less

  5. Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

    PubMed

    Gibson, Daniel A; Ma, Le

    2011-08-01

    Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab

  6. The Concept of Strategic Decisionmaking.

    ERIC Educational Resources Information Center

    Collier, Douglas J.

    Strategic decision-making literature is reviewed, and applications to colleges and universities are made. The key requirement for strategic decision-making is that decisions affect the entire organization. While strategic decision-making can occur at different levels within the organization, the specific strategic decisions available to the…

  7. Strategic Alliance Poker: Demonstrating the Importance of Complementary Resources and Trust in Strategic Alliance Management

    ERIC Educational Resources Information Center

    Reutzel, Christopher R.; Worthington, William J.; Collins, Jamie D.

    2012-01-01

    Strategic Alliance Poker (SAP) provides instructors with an opportunity to integrate the resource based view with their discussion of strategic alliances in undergraduate Strategic Management courses. Specifically, SAP provides Strategic Management instructors with an experiential exercise that can be used to illustrate the value creation…

  8. Strategic agility for nursing leadership.

    PubMed

    Shirey, Maria R

    2015-06-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change. In this article, the author discusses strategic agility as an important leadership competency and offers approaches for incorporating strategic agility in healthcare systems. A strategic agility checklist and infrastructure-building approach are presented.

  9. Strategic planning for neuroradiologists.

    PubMed

    Berlin, Jonathan W; Lexa, Frank J

    2012-08-01

    Strategic planning is becoming essential to neuroradiology as the health care environment continues to emphasize cost efficiency, teamwork and collaboration. A strategic plan begins with a mission statement and vision of where the neuroradiology division would like to be in the near future. Formalized strategic planning frameworks, such as the strengths, weaknesses, opportunities and threats (SWOT), and the Balanced Scorecard frameworks, can help neuroradiology divisions determine their current position in the marketplace. Communication, delegation, and accountability in neuroradiology is essential in executing an effective strategic plan. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Strategic Plan. Volume 1

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The purpose of this document is to present the strategic plan and associated organizational structure that the National Space Biomedical Research Institute (NSBRI) will utilize to achieve the defined mission and objectives provided by NASA. Much of the information regarding the background and establishment of the NSBRI by NASA has been provided in other documentation and will not be repeated in this Strategic Plan. This Strategic Plan is presented in two volumes. Volume I (this volume) begins with an Introduction (Section 2) that provides the Institute's NASA-defined mission and objectives, and the organizational structure adopted to implement these through three Strategic Programs: Countermeasure Research; Education, Training and Outreach; and Cooperative Research and Development. These programs are described in Sections 3 to 5. Each program is presented in a similar way, using four subsections: Goals and Objectives; Current Strategies; Gaps and Modifications; and Resource Requirements. Section 6 provides the administrative infrastructure and total budget required to implement the Strategic Programs and assures that they form a single cohesive plan. This plan will ensure continued success of the Institute for the next five years. Volume II of the Strategic Plan provides an in-depth analysis of the current and future strategic programs of the 12 current NSBRI teams, including their goals, objectives, mutual interactions and schedules.

  11. The Fund-Raising Role.

    ERIC Educational Resources Information Center

    Radock, Michael

    1980-01-01

    The college trustees' responsibility for fund-raising is outlined. Trustees are responsible for policy decisions that define the mission of the institution, that allocate development priorities to particular programs, or goals of the institution, and that provide the budget, the impetus, and the targets for a fund-raising campaign. Although…

  12. 78 FR 17924 - U.S. Strategic Command Strategic Advisory Group; Notice of Federal Advisory Committee Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

    ... DEPARTMENT OF DEFENSE Office of the Secretary U.S. Strategic Command Strategic Advisory Group... following federal advisory committee: U.S. Strategic Command Strategic Advisory Group. DATES: April 18, 2013..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

  13. Enhancing the Future Strategic Corporal

    DTIC Science & Technology

    2006-01-01

    with greater firepower than ever before, the Strategic Corporal will be charged with greater responsibility than ever before, while the potential for...translation of “Strategic Corporal ”, and the article responsible for popularizing the term, see General Charles C. Krulak, “The Strategic Corporal ...Quantico, Virginia 22134-5068 FUTURE WAR PAPER ENHANCING THE FUTURE STRATEGIC CORPORAL SUBMITTED IN PARTIAL FULFILLMENT OF THE

  14. Improvement of a yeast self-excising integrative vector by prevention of expression leakage of the intronated Cre recombinase gene during plasmid maintenance in Escherichia coli.

    PubMed

    Agaphonov, Michael O

    2017-12-01

    The use of plasmids possessing a regulatable gene coding for a site-specific recombinase together with its recognition sequences significantly facilitates genome manipulations since it allows self-excision of the portion of the genetic construct integrated into the host genome. Stable maintenance of such plasmids in Escherichia coli, which is used for plasmid preparation, requires prevention of recombinase synthesis in this host, which can be achieved by interrupting the recombinase gene with an intron. Based on this approach, Saccharomyces cerevisiae and Hansenula polymorpha self-excising vectors possessing intronated gene for Cre recombinase and its recognition sites (LoxP) were previously constructed. However, this work shows instability of the H. polymorpha vectors during plasmid maintenance in E. coli cells. This could be due to recombination between the loxP sites caused by residual expression of the cre gene. Prevention of translation reinitiation on an internal methionine codon completely solved this problem. A similar modification was made in a self-excising vector designed for S. cerevisiae. Apart from substantial improvement of yeast self-excising vectors, the obtained results also narrow down the essential part of Cre sequence. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Strategic Management in the Community College.

    ERIC Educational Resources Information Center

    Myran, Gunder A.

    1983-01-01

    Defines strategic management and discusses its role in community colleges, focusing on the components and methodology of strategic management, strategic and operational management function, management teams, and the need for strategic management. (DMM)

  16. Strategic Investments Overview

    NASA Technical Reports Server (NTRS)

    Comstock, Doug

    2004-01-01

    This viewgraph presentation provides an overview of the organizational hierarchy for strategic management and strategic investments at NASA. The presentation also relates these topics to the budgets it submits to Congress, strategies for space exploration research and development, and systems analysis.

  17. Conservation of strategic metals

    NASA Technical Reports Server (NTRS)

    Stephens, J. R.

    1982-01-01

    A long-range program in support of the aerospace industry aimed at reducing the use of strategic materials in gas turbine engines is discussed. The program, which is called COSAM (Conservation of Strategic Aerospace Materials), has three general objectives. The first objective is to contribute basic scientific understanding to the turbine engine technology bank so that our national security is not jeopardized if our strategic material supply lines are disrupted. The second objective is to help reduce the dependence of United States military and civilian gas turbine engines on worldwide supply and price fluctuations in regard to strategic materials. The third objective is, through research, to contribute to the United States position of preeminence in the world gas turbine engine markets by minimizing the acquisition costs and optimizing the performance of gas turbine engines. Three major research thrusts are planned: strategic element substitution; advanced processing concepts; and alternate material identification. Results from research and any required supporting technology will give industry the materials technology options it needs to make tradeoffs in material properties for critical components against the cost and availability impacts related to their strategic metal content.

  18. Strategic Talk in Film.

    PubMed

    Payr, Sabine; Skowron, Marcin; Dobrosovestnova, Anna; Trapp, Martin; Trappl, Robert

    2017-01-01

    Conversational robots and agents are being designed for educational and/or persuasive tasks, e.g., health or fitness coaching. To pursue such tasks over a long time, they will need a complex model of the strategic goal, a variety of strategies to implement it in interaction, and the capability of strategic talk. Strategic talk is incipient ongoing conversation in which at least one participant has the objective of changing the other participant's attitudes or goals. The paper is based on the observation that strategic talk can stretch over considerable periods of time and a number of conversational segments. Film dialogues are taken as a source to develop a model of the strategic talk of mentor characters. A corpus of film mentor utterances is annotated on the basis of the model, and the data are interpreted to arrive at insights into mentor behavior, especially into the realization and sequencing of strategies.

  19. Strategic Planning to Conduct Joint Force Network Operations: A Content Analysis of NETOPS Organizations Strategic Plans

    DTIC Science & Technology

    2007-03-01

    information dominance , Joint Network Operations (NETOPS) organizations need to be strategically aligned. As result, to enhance the capabilities-based effects of NETOPS and reduce our NETOP infrastructures susceptibility to compromise. Once the key organizations were identified, their strategic plans were analyzed using a structured content analysis framework. The results illustrated that the strategic plans were aligned with the community of interests tasking to conduct NETOPS. Further research is required into the strategic alignment beyond the strategic

  20. 75 FR 22561 - Federal Advisory Committee; United States Strategic Command Strategic Advisory Group; Charter...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Command Strategic Advisory Group; Charter Renewal AGENCY: Department of Defense (DoD). ACTION: Renewal of... Command Strategic Advisory Group (hereafter referred to as the Group). FOR FURTHER INFORMATION CONTACT... Chairman of the Joint Chiefs of Staff and the Commander of the U.S. Strategic Command independent advice...

  1. 76 FR 52642 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command.... Strategic Command Strategic Advisory Group. DATES: November 1, 2011, from 8 a.m. to 5 p.m. and November 2..., intelligence, and policy-related issues to the Commander, U.S. Strategic Command, during the development of the...

  2. Cultivating strategic thinking skills.

    PubMed

    Shirey, Maria R

    2012-06-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advancing organizational change, content includes evidence-based projects, tools, and resources that mobilize and sustain organizational change initiatives. In this article, the author presents an overview of strategic leadership and offers approaches for cultivating strategic thinking skills.

  3. FY17 Strategic Themes.

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

    Leland, Robert W.

    2017-03-01

    I am pleased to present this summary of the FY17 Division 1000 Science and Technology Strategic Plan. As this plan represents a continuation of the work we started last year, the four strategic themes (Mission Engagement, Bold Outcomes, Collaborative Environment, and Safety Imperative) remain the same, along with many of the goals. You will see most of the changes in the actions listed for each goal: We completed some actions, modified others, and added a few new ones. As I’ve stated previously, this is not a strategy to be pursued in tension with the Laboratory strategic plan. The Division 1000more » strategic plan is intended to chart our course as we strive to contribute our very best in service of the greater Laboratory strategy. I welcome your feedback and look forward to our dialogue about these strategic themes. Please join me as we move forward to implement the plan in the coming months.« less

  4. Strategic Talk in Film

    PubMed Central

    Payr, Sabine; Skowron, Marcin; Dobrosovestnova, Anna; Trapp, Martin; Trappl, Robert

    2017-01-01

    ABSTRACT Conversational robots and agents are being designed for educational and/or persuasive tasks, e.g., health or fitness coaching. To pursue such tasks over a long time, they will need a complex model of the strategic goal, a variety of strategies to implement it in interaction, and the capability of strategic talk. Strategic talk is incipient ongoing conversation in which at least one participant has the objective of changing the other participant’s attitudes or goals. The paper is based on the observation that strategic talk can stretch over considerable periods of time and a number of conversational segments. Film dialogues are taken as a source to develop a model of the strategic talk of mentor characters. A corpus of film mentor utterances is annotated on the basis of the model, and the data are interpreted to arrive at insights into mentor behavior, especially into the realization and sequencing of strategies. PMID:29375243

  5. The strategic security officer.

    PubMed

    Hodges, Charles

    2014-01-01

    This article discusses the concept of the strategic security officer, and the potential that it brings to the healthcare security operational environment. The author believes that training and development, along with strict hiring practices, can enable a security department to reach a new level of professionalism, proficiency and efficiency. The strategic officer for healthcare security is adapted from the "strategic corporal" concept of US Marine Corps General Charles C. Krulak which focuses on understanding the total force implications of the decisions made by the lowest level leaders within the Corps (Krulak, 1999). This article focuses on the strategic organizational implications of every security officer's decisions in the constantly changing and increasingly volatile operational environment of healthcare security.

  6. 7 CFR 25.202 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Procedure § 25.202 Strategic plan. (a) Principles of strategic plan. The strategic plan included in the application must be developed in accordance with the following four key principles: (1) Strategic vision for... institutions and individual citizens. (3) Economic opportunity, including job creation within the community and...

  7. Strategic Risk Assessment

    NASA Technical Reports Server (NTRS)

    Derleth, Jason; Lobia, Marcus

    2009-01-01

    This slide presentation provides an overview of the attempt to develop and demonstrate a methodology for the comparative assessment of risks across the entire portfolio of NASA projects and assets. It includes information about strategic risk identification, normalizing strategic risks, calculation of relative risk score, and implementation options.

  8. The Lisbon new international airport: The story of a decision-making process and the role of Strategic Environmental Assessment

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

    Partidario, Maria R., E-mail: mrp@civil.ist.utl.p; Coutinho, Miguel, E-mail: miguel.coutinho@ua.p

    2011-04-15

    This is the brief story of a decision process and the role of Strategic Environmental Assessment in government political decision-making. Following a prolonged, and agitated, decision process, initiated in the 1960s, the Government of Portugal in 2005 took the final decision to build the new international airport of Lisbon at the controversial location of Ota, 40 km north of Lisbon. The detailed project design and EIA were started. However this decision would change in 2007 due to the challenge raised by a private sponsored study that identified an alternative location for the airport at Campo de Tiro de Alcochete (CTA).more » This new site, which had never been considered as an option before, appeared to avoid many of the problems that caused public controversy at the Ota site. The Government, pressured by this challenge, promoted a strategic comparative assessment between the two sites. The result of this study was the choice of CTA as the preferred location. This paper discusses this radical change in the decision from a socio-political perspective. It will highlight the relevance of Strategic Environmental Assessment (SEA), and the strategic and constructive approach it enables in mega-project decision-making.« less

  9. Successful Community College Fund-Raising Programs

    ERIC Educational Resources Information Center

    Anderson, Spencer

    2005-01-01

    This article describes a study whose primary purposes were to determine the characteristics of an effective fund-raising program, the marketing practices that contribute to the success of a fund-raising program, and factors of the development system's influence on a fund-raising program. This study utilized a Delphi research instrument. Initially,…

  10. Strategic Partnerships in Higher Education

    ERIC Educational Resources Information Center

    Ortega, Janet L.

    2013-01-01

    The purpose of this study was to investigate the impacts of strategic partnerships between community colleges and key stakeholders; to specifically examine strategic partnerships; leadership decision-making; criteria to evaluate strategic partnerships that added value to the institution, value to the students, faculty, staff, and the local…

  11. Strategic Planning and Financial Management

    ERIC Educational Resources Information Center

    Conneely, James F.

    2010-01-01

    Strong financial management is a strategy for strategic planning success in student affairs. It is crucial that student affairs professionals understand the necessity of linking their strategic planning with their financial management processes. An effective strategic planner needs strong financial management skills to implement the plan over…

  12. The Possibilities of Strategic Finance

    ERIC Educational Resources Information Center

    Chaffee, Ellen

    2010-01-01

    Strategic finance is aligning financial decisions--regarding revenues, creating and maintaining institutional assets, and using those assets--with the institution's mission and strategic plan. The concept known as "strategic finance" increasingly is being seen as a useful perspective for helping boards and presidents develop a sustainable…

  13. Strategic and non-strategic problem gamblers differ on decision-making under risk and ambiguity.

    PubMed

    Lorains, Felicity K; Dowling, Nicki A; Enticott, Peter G; Bradshaw, John L; Trueblood, Jennifer S; Stout, Julie C

    2014-07-01

    To analyse problem gamblers' decision-making under conditions of risk and ambiguity, investigate underlying psychological factors associated with their choice behaviour and examine whether decision-making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. Cross-sectional study. Out-patient treatment centres and university testing facilities in Victoria, Australia. Thirty-nine problem gamblers and 41 age, gender and estimated IQ-matched controls. Decision-making tasks included the Iowa Gambling Task (IGT) and a loss aversion task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. Overall, problem gamblers performed more poorly than controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and their IGT decisions were associated with heightened attention to gains (P = 0.003) and less consistency (P = 0.002). Strategic problem gamblers did not differ from matched controls on either decision-making task, but non-strategic problem gamblers performed worse on both the IGT (P = 0.006) and the loss aversion task (P = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. Problem gamblers demonstrated poor decision-making under conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non-strategic (e.g. electronic gaming machines) problem gamblers differed in decision-making and the underlying psychological processes associated with their decisions. © 2014 Society for the Study of Addiction.

  14. 29 CFR 780.123 - Raising of bees.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Raising of bees. 780.123 Section 780.123 Labor Regulations... Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.123 Raising of bees. The term “raising of * * * bees” refers to all of those activities customarily performed in connection with the...

  15. 29 CFR 780.123 - Raising of bees.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Raising of bees. 780.123 Section 780.123 Labor Regulations... Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.123 Raising of bees. The term “raising of * * * bees” refers to all of those activities customarily performed in connection with the...

  16. 29 CFR 780.123 - Raising of bees.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Raising of bees. 780.123 Section 780.123 Labor Regulations... Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.123 Raising of bees. The term “raising of * * * bees” refers to all of those activities customarily performed in connection with the...

  17. 29 CFR 780.123 - Raising of bees.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Raising of bees. 780.123 Section 780.123 Labor Regulations... Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.123 Raising of bees. The term “raising of * * * bees” refers to all of those activities customarily performed in connection with the...

  18. 29 CFR 780.123 - Raising of bees.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Raising of bees. 780.123 Section 780.123 Labor Regulations... Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.123 Raising of bees. The term “raising of * * * bees” refers to all of those activities customarily performed in connection with the...

  19. The Strategic Reader.

    ERIC Educational Resources Information Center

    Devine, James T., Ed.; And Others

    1986-01-01

    To add a foundation to the growing excitement among educators about the central role they play in helping learners become strategic readers, the articles in this thematic journal provide insight into current reading theory and practice. Richard Telfer's article reviews research on strategic reading and clarifies what is meant by the phrase…

  20. String Vacuous Overt Verb Raising.

    ERIC Educational Resources Information Center

    Koisumi, Masatoshi

    2000-01-01

    Presents evidence for overt verb raising in Japanese, thereby defending the validity of the head parameter with its two values (head initial and head final). Explores consequences of the overt verb raising analysis of Japanese to various aspects of syntactic theory. (Author/VWL)

  1. FY16 Strategic Themes.

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

    Leland, Robert W.

    2017-03-01

    I am pleased to present this summary of the Division 1000 Science and Technology Strategic Plan. This plan was created with considerable participation from all levels of management in Division 1000, and is intended to chart our course as we strive to contribute our very best in service of the greater Laboratory strategy. The plan is characterized by four strategic themes: Mission Engagement, Bold Outcomes, Collaborative Environment, and the Safety Imperative. Each theme is accompanied by a brief vision statement, several goals, and planned actions to support those goals throughout FY16. I want to be clear that this is notmore » a strategy to be pursued in tension with the Laboratory strategic plan. Rather, it is intended to describe “how” we intend to show up for the “what” described in Sandia’s Strategic Plan. I welcome your feedback and look forward to our dialogue about these strategic themes. Please join me as we move forward to implement the plan in the coming year.« less

  2. Reforming Pentagon Strategic Decisionmaking. Strategic Forum. Number 221, July 2006

    DTIC Science & Technology

    2006-07-01

    capability that would improve Pentagon decisionmaking. Blink and Think It is commonly assumed that people can and should make decisions as rationally ... rationality ,” which not only helps them make decisions but also introduces a range of nonrational psychologi- cal factors into their thinking. An otherwise...decisionmaking shortcuts that limit their ability to make rational decisions . Strategic Forum No. 221July 2006 Institute for National Strategic Studies

  3. A strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece.

    PubMed

    Petri, Aspasia; Karabetsos, Efthymios

    2018-06-08

    Herein, the strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece is presented. This framework has been designed and promoted by the competent national regulatory authority, which is the Greek Atomic Energy Commission (EEAE). The aim is to ensure a common understanding regarding ultraviolet radiation (UVR) and artificial tanning among the artificial tanning professionals, the stakeholders and the general public. The strategic framework is founded on the international organizations' recommendations, the EU requirements and the relevant technical standards. It is comprised of three autonomous but interconnected components: A) A sunbed operators' e-training course and certification process, B) A code of practice addressed individually to the business owners, the sunbeds operators and the sunbeds users, C) Communication strategies aiming to raise awareness regarding UVR and artificial tanning to all the interested parties. The artificial tanning safety culture framework presented here is the policy option that EEAE undertook and it is embedded in the upcoming legislation and regulations for the provision of artificial tanning services in Greece. EEAE considers that the structure of the artificial tanning safety culture strategic framework will serve as the guide for the development and promotion of relevant safety culture strategic frameworks for the provision of aesthetic/wellness services that utilize other non-ionizing radiation sources, which currently don't exist. © 2018 IOP Publishing Ltd.

  4. Rising Goals for Raising Money.

    ERIC Educational Resources Information Center

    Fickes, Michael

    2000-01-01

    Discusses the increasing use of multiple-year capital fund raising campaigns to help colleges and universities defray the costs of attracting new students and quality faculty. An example details one university's changing goal structure to adjust to early success in its capital fund raising campaign. (GR)

  5. Strategic behaviour of institutional providers in mental handicapped care in the Netherlands.

    PubMed

    Van Harten, Willem H; Veldhuis, Marleen J M; Hoeksma, Bernhard H; Krabbendam, Koos J

    2007-01-01

    The purpose of this paper is to describe an inventory of the strategic responses of institutional providers of mental handicapped care to the strengthening of consumer choice through a personal care budget (PCB). Semi structured interviews were conducted among 26 providers covering 52 per cent of the total market volume of about 100,000 clients annually. A representative number of providers was included; on average a percentage below the national average of PCB users was found to be served. Of the 26 providers, 16 indicated adaption to their strategy in response to expected consumer empowerment The actual deployment of this response in the organisations seemed not to be very thorough or explicit. Surprisingly, as a growing part of PCB-clients choose alternative providers, no concerns were raised concerning the possible emergence of new service providers. Although the market share of PCB users is growing fast and existing providers do not seem to absorb this accordingly, a lack of market analysis and strategic behaviour of the traditional providers in response to this development was found. Based on this research growth of market shares of disruptive service providers can very well be anticipated.

  6. Department of State Strategic Planning Workshop II. Center for Strategic Leadership Issue Paper, Volume 01-02

    DTIC Science & Technology

    2002-04-01

    Strategic Leadership 650 Wright Avenue Carlisle, PA 170l3-5049 OFFICIAL BUSINESS DEPARTMENT OF STATE STRATEGIC PLANNING WORKSHOP II U.S. ARMY WAR COLLEGE CSL 4 ...April 2002 Issues Paper 01-02 Department of State Strategic Planning Workshop II By Colonel Jeffrey C. Reynolds A State Department request, made...at the senior level, asked the Army Chief of Staff if the Army could help State improve its capacity to undertake strategic planning. In April

  7. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB

    PubMed Central

    2012-01-01

    The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural) and explicit (declarative) memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory. PMID:22583753

  8. Being Strategic in HE Management

    ERIC Educational Resources Information Center

    West, Andrew

    2008-01-01

    The call to be strategic--and with it the concept of strategic management--can bring to mind a wide range of definitions, and there is now a huge array of academic literature supporting the different schools of thought. At a basic level, however, strategic thinking is probably most simply about focusing on the whole, rather than the part. In…

  9. Strategic management process in hospitals.

    PubMed

    Zovko, V

    2001-01-01

    Strategic management is concerned with strategic choices and strategic implementation; it provides the means by which organizations meet their objectives. In the case of hospitals it helps executives and all employees to understand the real purpose and long term goals of the hospital. Also, it helps the hospital find its place in the health care service provision chain, and enables the hospital to coordinate its activities with other organizations in the health care system. Strategic management is a tool, rather than a solution, that helps executives to identify root causes of major problems in the hospital.

  10. Developing strategic thinking in senior management.

    PubMed

    Zabriskie, N B; Huellmantel, A B

    1991-12-01

    Chief Executive Officers have recently stated that their greatest staffing challenge for the 1990s is the development of strategic leadership in their senior management. In order to do this, it is necessary to identify the substance of strategic thinking, and the capabilities that must be mastered. Writers on strategy have identified six major elements of strategic thinking and these have been organized to reveal the tasks, questions, decisions, and skills that senior executives must acquire in order to lead their organizations strategically. Finally, the article identifies training programme elements which are used by Directors of Manpower Development to develop strategic leadership ability.

  11. Symposium: Governing Boards--Raising Consciousness

    ERIC Educational Resources Information Center

    Academic Questions, 2007

    2007-01-01

    "What Works in Higher Education Reform: A Report from the Front," the twelfth annual national conference of the National Association of Scholars, took place November 17-19, 2006, in Cambridge, Massachusetts. One panel, "Governing Boards: Raising Consciousness," examined the role governing boards do and can play in raising awareness on campus and…

  12. Strategic Planning with Critical Success Factors and Future Scenarios: An Integrated Strategic Planning Framework

    DTIC Science & Technology

    2010-11-01

    Implementing the Process by David Fogg [ Fogg 1994]. 6 Strategic goals typically reflect the primary goals of an organization or enterprise and imply a...method, such as the one described by Fogg in Team-Based Strategic Planning: A Com- plete Guide to Structuring, Facilitating, and Implementing the...Process, can provide ready recep- tors for non-CSF oriented information [ Fogg 1994]. If an organization is not adept at strategic planning, it is highly

  13. Metallographic and fractographic observations of posttest creep-fatigue specimens of weld-deposited Type 308 CRE stainless steel

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

    Williams, M. W.

    Type 308 CRE stainless steel weld specimens were subjected to metallographic and fractographic analysis after failure in elevated-temperature (593/sup 0/C) creep-fatigue tests. The failure mode for specimens tested under continuous-cycle fatigue conditions was predominantly transgranular. When the test cycle was modified to include a hold time at the maximum tensile strain, the failure mode became predominantly interphase. Sigma phase was observed within the delta-ferrite regions in the weld. However, the presence of sigma phase did not appear to affect the failure mode.

  14. Strategic planning by independent community pharmacies.

    PubMed

    Harrison, Donald L

    2005-01-01

    (1) To assess the degree and level of use of the strategic planning process (none, partly, fully) by independent community pharmacy owners/managers and (2) to evaluate the relationships between independent community pharmacy owners/managers' level of strategic planning and indicators of pharmacy performance; including new and refill prescriptions filled, gross margin, rated patient care performance, rated dispensing performance, rated non-pharmacy performance, and rated financial performance. Cross-sectional study. United States. Nationwide random sample of 1,250 owners/managers of independent community pharmacies. Mailed survey. Quality of strategic planning conducted; pharmacy performance measures. Only 141 of 527 (26.8%) usable responses indicated use of some (77 pharmacies, 54.6%) or all (64 pharmacies, 45.4%) of the seven steps typical of strategic planning. Significant associations were observed between the level of strategic planning use and all pharmacy performance variables assessed, including indicators such as greater numbers of new and refill prescriptions dispensed, gross margins, patient care performance, dispensing performance, non-pharmacy performance, and financial performance. Greater ratings of pharmacy performance were significantly associated with the level of strategic planning use. Respondents who fully used strategic planning had significantly higher indicators than partial users; respondents who partly used the process had significantly higher ratings than respondents who did not conduct strategic planning.

  15. Program Manager: Journal of the Defense Systems Management College. Volume 23, Number 1, January-February 1994

    DTIC Science & Technology

    1994-02-01

    Jones, Jr. PROGRAM MANAGER Managing Editor Esther M. Farria Art Director Greg Caruth Typography and Design Paula Croisetlere Program Manager (ISSN 0199...Company bombers to implement the strategic organization - President Clayton 1. Brukner commu- bombing doctrine. This would take all brand -new cre

  16. 76 FR 60811 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group; Correction AGENCY: Department of Defense. ACTION: Notice of Advisory Committee... Command Strategic Advisory Group gave notice of a meeting to be held on November 1, 2011, from 8 a.m. to 5...

  17. The PVCC Strategic Plan.

    ERIC Educational Resources Information Center

    Piedmont Virginia Community Coll., Charlottesville, VA.

    Presents Piedmont Virginia Community College's (PVCC's) strategic plan. Contains the following chapters: (1) introduction; (2) statement of mission; (3) summary of the college's strategic initiatives: funding, organization, faculty and staff, curriculum and instruction, enrollment management, students and student services, facilities, technology,…

  18. Effective Fund-Raising for Non-profit Camps.

    ERIC Educational Resources Information Center

    Larson, Paula

    1998-01-01

    Identifies and describes strategies for effective fundraising: imagining the possibilities, identifying fund-raising sources, targeting fund-raising efforts, maximizing time by utilizing public relations efforts and involving staff, writing quality proposals and requests, and staying educated on fund-raising topics. Sidebars describe planned…

  19. The paradox of strategic environmental assessment

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

    Bidstrup, Morten, E-mail: bidstrup@plan.aau.dk; Hansen, Anne Merrild, E-mail: merrild@plan.aau.dk

    Strategic Environmental Assessment (SEA) is a tool that can facilitate sustainable development and improve decision-making by introducing environmental concern early in planning processes. However, various international studies conclude that current planning practice is not taking full advantage of the tool, and we therefore define the paradox of SEA as the methodological ambiguity of non-strategic SEA. This article explores causality through at three-step case study on aggregates extraction planning in Denmark, which consists of a document analysis; a questionnaire survey and follow-up communication with key planners. Though the environmental reports on one hand largely lack strategic considerations, practitioners express an inherentmore » will for strategy and reveal that their SEAs in fact have been an integrated part of the planning process. Institutional context is found to be the most significant barrier for a strategy and this suggests that non-strategic planning setups can prove more important than non-strategic planning in SEA practice. Planners may try to execute strategy within the confinements of SEA-restricted planning contexts; however, such efforts can be overlooked if evaluated by a narrow criterion for strategy formation. Consequently, the paradox may also spark from challenged documentation. These findings contribute to the common understanding of SEA quality; however, further research is needed on how to communicate and influence the strategic options which arguably remain inside non-strategic planning realities. - Highlights: • International studies conclude that SEAs are not strategic. = The paradox of SEA. • Even on the highest managerial level, some contexts do not leave room for strategy. • Non-strategic SEA can derive from challenged documentation. • Descriptive and emergent strategy formation can, in practice, be deemed non-strategic.« less

  20. Successful strategic planning: creating clarity.

    PubMed

    Adams, Jim

    2005-01-01

    Most healthcare organizations have a strategic plan of some kind. Many of these organizations also have difficulty translating their strategic plan into specific actions that result in successful performance. In the worst cases, this can jeopardize the viability of the organization. The trouble lies in a lack of clarity in what a strategic plan is and what it should do for the organization. This article will answer key questions such as: What is strategy and how does it fit with other commonly used constructs such as mission, vision, and goals? What criteria can be used to determine if something is truly strategic to the organization? What are the phases of the strategy lifecycle? How do approaches for dealing with uncertainty, such as scenario planning, fit with organizational strategic planning? How can a meaningful IT strategy be developed if the organization strategy is lacking? What principles should guide a good IT planning process?

  1. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

    USDA-ARS?s Scientific Manuscript database

    Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

  2. Joint Decisions on Production and Pricing with Strategic Consumers for Green Crowdfunding Products.

    PubMed

    Chen, Yuting; Zhang, Rong; Liu, Bin

    2017-09-20

    Green crowdfunding is developing as a novel and popular transaction method, which can largely improve the efficiency of raising initial funds and selling innovative green products or services. In this paper, we explore the creator's joint decisions regarding green crowdfunding products of different quality levels that can sufficiently satisfy consumer preferences. Firstly, considering the characteristics of a green crowdfunding product, we present four pricing strategies when substitutes exist. Then we propose the optimal pricing strategies to maximize the total profit for the creator under different circumstances, facing strategic and myopic consumers. Finally, for the heterogeneity of consumer valuations, we compare the total profits of the four pricing strategies under different values of the substitution coefficient to obtain the optimal pricing and product strategies under the coexistence of strategic and myopic consumers. According to the result, we find that when the fraction of high-type consumers and the gap between high and low valuations is big, or when they are both small, traditional single pricing shows its benefit. However, when the green crowdfunding products are better than their substitute, a line of green products is more likely to be optimal.

  3. Joint Decisions on Production and Pricing with Strategic Consumers for Green Crowdfunding Products

    PubMed Central

    Chen, Yuting; Zhang, Rong

    2017-01-01

    Green crowdfunding is developing as a novel and popular transaction method, which can largely improve the efficiency of raising initial funds and selling innovative green products or services. In this paper, we explore the creator’s joint decisions regarding green crowdfunding products of different quality levels that can sufficiently satisfy consumer preferences. Firstly, considering the characteristics of a green crowdfunding product, we present four pricing strategies when substitutes exist. Then we propose the optimal pricing strategies to maximize the total profit for the creator under different circumstances, facing strategic and myopic consumers. Finally, for the heterogeneity of consumer valuations, we compare the total profits of the four pricing strategies under different values of the substitution coefficient to obtain the optimal pricing and product strategies under the coexistence of strategic and myopic consumers. According to the result, we find that when the fraction of high-type consumers and the gap between high and low valuations is big, or when they are both small, traditional single pricing shows its benefit. However, when the green crowdfunding products are better than their substitute, a line of green products is more likely to be optimal. PMID:28930198

  4. Strategic Decision Making Paradigms: A Primer for Senior Leaders

    DTIC Science & Technology

    2009-07-01

    decision making . STRATEGIC DECISION MAKING Strategic Change: There are several strategic...influenced by stakeholders outside of the organization. The Ontology of Strategic Decision Making . Strategic decisions are non-routine and involve...Coates USAWC, July 2009 5 The Complexity of Strategic Decision Making Strategic decisions entail “ill-structured,”6 “messy” or

  5. Raising the Titanic.

    ERIC Educational Resources Information Center

    Baker, Romona

    1990-01-01

    Described is an activity in which groups of students investigate engineering principles by writing a feasibility study to raise the luxury liner, Titanic. The problem statement and directions, and suggestions for problem solutions are included. (CW)

  6. Children's strategic theory of mind.

    PubMed

    Sher, Itai; Koenig, Melissa; Rustichini, Aldo

    2014-09-16

    Human strategic interaction requires reasoning about other people's behavior and mental states, combined with an understanding of their incentives. However, the ontogenic development of strategic reasoning is not well understood: At what age do we show a capacity for sophisticated play in social interactions? Several lines of inquiry suggest an important role for recursive thinking (RT) and theory of mind (ToM), but these capacities leave out the strategic element. We posit a strategic theory of mind (SToM) integrating ToM and RT with reasoning about incentives of all players. We investigated SToM in 3- to 9-y-old children and adults in two games that represent prevalent aspects of social interaction. Children anticipate deceptive and competitive moves from the other player and play both games in a strategically sophisticated manner by 7 y of age. One game has a pure strategy Nash equilibrium: In this game, children achieve equilibrium play by the age of 7 y on the first move. In the other game, with a single mixed-strategy equilibrium, children's behavior moved toward the equilibrium with experience. These two results also correspond to two ways in which children's behavior resembles adult behavior in the same games. In both games, children's behavior becomes more strategically sophisticated with age on the first move. Beyond the age of 7 y, children begin to think about strategic interaction not myopically, but in a farsighted way, possibly with a view to cooperating and capitalizing on mutual gains in long-run relationships.

  7. Collaborative Strategic Planning: Myth or Reality?

    ERIC Educational Resources Information Center

    Mbugua, Flora; Rarieya, Jane F. A.

    2014-01-01

    The concept and practice of strategic planning, while entrenched in educational institutions in the West, is just catching on in Kenya. While literature emphasizes the importance of collaborative strategic planning, it does not indicate the challenges presented by collaboratively engaging in strategic planning. This article reports on findings of…

  8. Neural mechanisms mediating degrees of strategic uncertainty.

    PubMed

    Nagel, Rosemarie; Brovelli, Andrea; Heinemann, Frank; Coricelli, Giorgio

    2018-01-01

    In social interactions, strategic uncertainty arises when the outcome of one's choice depends on the choices of others. An important question is whether strategic uncertainty can be resolved by assessing subjective probabilities to the counterparts' behavior, as if playing against nature, and thus transforming the strategic interaction into a risky (individual) situation. By means of functional magnetic resonance imaging with human participants we tested the hypothesis that choices under strategic uncertainty are supported by the neural circuits mediating choices under individual risk and deliberation in social settings (i.e. strategic thinking). Participants were confronted with risky lotteries and two types of coordination games requiring different degrees of strategic thinking of the kind 'I think that you think that I think etc.' We found that the brain network mediating risk during lotteries (anterior insula, dorsomedial prefrontal cortex and parietal cortex) is also engaged in the processing of strategic uncertainty in games. In social settings, activity in this network is modulated by the level of strategic thinking that is reflected in the activity of the dorsomedial and dorsolateral prefrontal cortex. These results suggest that strategic uncertainty is resolved by the interplay between the neural circuits mediating risk and higher order beliefs (i.e. beliefs about others' beliefs). © The Author(s) (2017). Published by Oxford University Press.

  9. Neural mechanisms mediating degrees of strategic uncertainty

    PubMed Central

    Nagel, Rosemarie; Brovelli, Andrea; Heinemann, Frank

    2018-01-01

    Abstract In social interactions, strategic uncertainty arises when the outcome of one’s choice depends on the choices of others. An important question is whether strategic uncertainty can be resolved by assessing subjective probabilities to the counterparts’ behavior, as if playing against nature, and thus transforming the strategic interaction into a risky (individual) situation. By means of functional magnetic resonance imaging with human participants we tested the hypothesis that choices under strategic uncertainty are supported by the neural circuits mediating choices under individual risk and deliberation in social settings (i.e. strategic thinking). Participants were confronted with risky lotteries and two types of coordination games requiring different degrees of strategic thinking of the kind ‘I think that you think that I think etc.’ We found that the brain network mediating risk during lotteries (anterior insula, dorsomedial prefrontal cortex and parietal cortex) is also engaged in the processing of strategic uncertainty in games. In social settings, activity in this network is modulated by the level of strategic thinking that is reflected in the activity of the dorsomedial and dorsolateral prefrontal cortex. These results suggest that strategic uncertainty is resolved by the interplay between the neural circuits mediating risk and higher order beliefs (i.e. beliefs about others’ beliefs). PMID:29228378

  10. Arity Raising in Manticore

    NASA Astrophysics Data System (ADS)

    Bergstrom, Lars; Reppy, John

    Compilers for polymorphic languages are required to treat values in programs in an abstract and generic way at the source level. The challenges of optimizing the boxing of raw values, flattening of argument tuples, and raising the arity of functions that handle complex structures to reduce memory usage are old ones, but take on newfound import with processors that have twice as many registers. We present a novel strategy that uses both control-flow and type information to provide an arity raising implementation addressing these problems. This strategy is conservative - no matter the execution path, the transformed program will not perform extra operations.

  11. Manage "Human Capital" Strategically

    ERIC Educational Resources Information Center

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  12. Fund Raising and Public College Trustees.

    ERIC Educational Resources Information Center

    Farley, Eileen

    1986-01-01

    Public college trustees' responsibilities in fund raising include ensuring that private fund-raising takes place, setting policies and priorities, linking private philanthropy and public funding authorities, assuring college support of alumni and public relations activities, furthering public confidence, and giving. (MSE)

  13. Effects of rolipram, a phosphodiesterase 4 inhibitor, in combination with imipramine on depressive behavior, CRE-binding activity and BDNF level in learned helplessness rats.

    PubMed

    Itoh, Tetsuji; Tokumura, Miwa; Abe, Kohji

    2004-09-13

    The brain cAMP regulating system and its downstream elements play a pivotal role in the therapeutic effects of antidepressants. We previously reported the increase in activities of phosphodiesterase 4, a major phosphodiesterase isozyme hydrolyzing cAMP, in the frontal cortex and hippocampus of learned helplessness rats, an animal model for depression. The present study was undertaken to examine the combination of effects of rolipram, a phosphodiesterase 4 inhibitor, with imipramine, a typical tricyclic antidepressant, on depressive behavior in learned helplessness rats. Concurrently, cAMP-response element (CRE)-binding activity and brain-derived neurotrophic factor (BDNF) levels related to the therapeutic effects of antidepressants were determined. Repeated administration of imipramine (1.25-10 mg/kg, i.p.) or rolipram (1.25 mg/kg, i.p.) reduced the number of escape failures in learned helplessness rats. Imipramine could not completely ameliorate the escape behavior to a level similar to that of non-stressed rats even at 10 mg/kg. However, repeated coadministration of rolipram with imipramine (1.25 and 2.5 mg/kg, respectively) almost completely eliminated the escape failures in learned helplessness rats. The reduction of CRE-binding activities and BDNF levels in the frontal cortex or hippocampus in learned helplessness rats were ameliorated by treatment with imipramine or rolipram alone. CRE-binding activities and/or BDNF levels of the frontal cortex and hippocampus were significantly increased by treatment with a combination of rolipram and imipramine compared to those in imipramine-treated rats. These results indicated that coadministration of phosphodiesterase type 4 inhibitors with antidepressants may be more effective for depression therapy and suggest that elevation of the cAMP signal transduction pathway is involved in the antidepressive effects.

  14. Strategic Leadership in Schools

    ERIC Educational Resources Information Center

    Williams, Henry S.; Johnson, Teryl L.

    2013-01-01

    Strategic leadership is built upon traits and actions that encompass the successful execution of all leadership styles. In a world that is rapidly changing, strategic leadership in schools guides school leader through assuring constant improvement process by anticipating future trends and planning for them and noting that plans must be flexible to…

  15. Sources and Information: Strategic Management.

    ERIC Educational Resources Information Center

    Palmer, Jim

    1983-01-01

    Provides an annotated bibliography of ERIC documents on strategic management, with emphasis on institutional responses to change, the role of the administrator in strategic management, budgeting and financial management, and institutional planning. (DMM)

  16. Characteristics of Useful and Practical Organizational Strategic Plans

    ERIC Educational Resources Information Center

    Kaufman, Roger

    2014-01-01

    Most organizational strategic plans are not strategic but rather tactical or operational plans masquerading as "strategic." This article identifies the basic elements required in a useful and practical strategic plan and explains why they are important.

  17. 12 CFR 228.27 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Strategic plan. 228.27 Section 228.27 Banks and... REINVESTMENT (REGULATION BB) Standards for Assessing Performance § 228.27 Strategic plan. (a) Alternative...(s) under a strategic plan if: (1) The bank has submitted the plan to the Board as provided for in...

  18. 23 CFR 1335.6 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Strategic plan. 1335.6 Section 1335.6 Highways NATIONAL... § 1335.6 Strategic plan. A strategic plan shall— (a) Be a multi-year plan that identifies and prioritizes... performance-based measures by which progress toward those goals will be determined; and (c) Be submitted to...

  19. 13 CFR 313.6 - Strategic Plans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Strategic Plans. 313.6 Section 313... § 313.6 Strategic Plans. (a) General. An Impacted Community that intends to apply for a grant for implementation assistance under § 313.7 shall develop and submit a Strategic Plan to EDA for evaluation and...

  20. 13 CFR 313.6 - Strategic Plans.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Strategic Plans. 313.6 Section 313... § 313.6 Strategic Plans. (a) General. An Impacted Community that intends to apply for a grant for implementation assistance under § 313.7 shall develop and submit a Strategic Plan to EDA for evaluation and...

  1. Strategic planning: today's hot buttons.

    PubMed

    Bohlmann, R C

    1998-01-01

    The first generation of mergers and managed care hasn't slowed down group practices' need for strategic planning. Even groups that already went through one merger are asking about new mergers or ownership possibilities, the future of managed care, performance standards and physician unhappiness. Strategic planning, including consideration of bench-marking, production of ancillary services and physician involvement, can help. Even if only a short, general look at the future, strategic planning shows the proactive leadership needed in today's environment.

  2. 12 CFR 25.27 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Strategic plan. 25.27 Section 25.27 Banks and... DEPOSIT PRODUCTION REGULATIONS Regulations Standards for Assessing Performance § 25.27 Strategic plan. (a... assessment area(s) under a strategic plan if: (1) The bank has submitted the plan to the OCC as provided for...

  3. 12 CFR 345.27 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Strategic plan. 345.27 Section 345.27 Banks and... REINVESTMENT Standards for Assessing Performance § 345.27 Strategic plan. (a) Alternative election. The FDIC... strategic plan if: (1) The bank has submitted the plan to the FDIC as provided for in this section; (2) The...

  4. Creating Strategic Visions

    DTIC Science & Technology

    1990-10-15

    3010 o, AuTOVON 242-3010. - =n~m~m i ma ll lil~ m mm m i mii FOREWORD This futures study presents an analysis and discussion of a program used at the U.S...Operations Research Society, and The Planning Forum . iv CREATING STRATEGIC VISIONS 1 Introduction. The United States Army War College (USAWC) prepares its...consideration and time must be given to a program that attempts to help these potential leaders learn how to create strategic visions. In this paper

  5. Software Engineering in Ada

    DTIC Science & Technology

    1988-03-22

    and es out of the frame-you DO NOT re- raise the exception. t mru to the point where the excep- tion was raised. You can be cre- UNUUAUY ative with...type we the tesis for equality and inequality and the assignment operation. unless the type is limited.. in which case no operations awe implicitly

  6. Raising Better Boys.

    ERIC Educational Resources Information Center

    Canada, Geoffrey

    2000-01-01

    The author of "Reaching Up For Manhood" discusses troubling social/environmental conditions confronting boys. Raising better boys requires caring adults, safer risk-taking situations, positive reinforcement, and role models. Parents should monitor boys' media exposure, provide moral education, broaden their cultural and natural-world…

  7. NASA strategic plan

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The NASA Strategic Plan is a living document. It provides far-reaching goals and objectives to create stability for NASA's efforts. The Plan presents NASA's top-level strategy: it articulates what NASA does and for whom; it differentiates between ends and means; it states where NASA is going and what NASA intends to do to get there. This Plan is not a budget document, nor does it present priorities for current or future programs. Rather, it establishes a framework for shaping NASA's activities and developing a balanced set of priorities across the Agency. Such priorities will then be reflected in the NASA budget. The document includes vision, mission, and goals; external environment; conceptual framework; strategic enterprises (Mission to Planet Earth, aeronautics, human exploration and development of space, scientific research, space technology, and synergy); strategic functions (transportation to space, space communications, human resources, and physical resources); values and operating principles; implementing strategy; and senior management team concurrence.

  8. Crew and Thermal Systems Strategic Communications Initiatives in Support of NASA's Strategic Goals

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.; Lamberth, Erika Guillory; Jennings, Mallory A.

    2012-01-01

    NASA has defined strategic goals to invest in next-generation technologies and innovations, inspire students to become the future leaders of space exploration, and expand partnerships with industry and academia around the world. The Crew and Thermal Systems Division (CTSD) at the NASA Johnson Space Center actively supports these NASA initiatives. In July 2011, CTSD created a strategic communications team to communicate CTSD capabilities, technologies, and personnel to external technical audiences for business development and collaborative initiatives, and to students, educators, and the general public for education and public outreach efforts. This paper summarizes the CTSD Strategic Communications efforts and metrics through the first half of fiscal year 2012 with projections for end of fiscal year data.

  9. Crew and Thermal Systems Strategic Communications Initiatives in Support of NASA's Strategic Goals

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.

    2012-01-01

    NASA has defined strategic goals to invest in next-generation technologies and innovations, to inspire students to become the future leaders of space exploration, and to expand partnerships with industry and academia around the world. The Crew and Thermal Systems Division (CTSD) at the NASA Johnson Space Center actively supports these NASA initiatives. In July 2011, CTSD created a strategic communications team to communicate CTSD capabilities, technologies, and personnel to internal NASA and external technical audiences for business development and collaborative initiatives, and to students, educators, and the general public for education and public outreach efforts. This paper summarizes the CTSD Strategic Communications efforts and metrics through the first nine months of fiscal year 2012.

  10. 28 CFR 902.2 - Raising disputes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Raising disputes. 902.2 Section 902.2 Judicial Administration NATIONAL CRIME PREVENTION AND PRIVACY COMPACT COUNCIL DISPUTE ADJUDICATION PROCEDURES § 902.2 Raising disputes. (a) Cognizable disputes may be based upon: (1) A claim that the Council...

  11. What does God know? Supernatural agents' access to socially strategic and non-strategic information.

    PubMed

    Purzycki, Benjamin G; Finkel, Daniel N; Shaver, John; Wales, Nathan; Cohen, Adam B; Sosis, Richard

    2012-07-01

    Current evolutionary and cognitive theories of religion posit that supernatural agent concepts emerge from cognitive systems such as theory of mind and social cognition. Some argue that these concepts evolved to maintain social order by minimizing antisocial behavior. If these theories are correct, then people should process information about supernatural agents' socially strategic knowledge more quickly than non-strategic knowledge. Furthermore, agents' knowledge of immoral and uncooperative social behaviors should be especially accessible to people. To examine these hypotheses, we measured response-times to questions about the knowledge attributed to four different agents--God, Santa Claus, a fictional surveillance government, and omniscient but non-interfering aliens--that vary in their omniscience, moral concern, ability to punish, and how supernatural they are. As anticipated, participants respond more quickly to questions about agents' socially strategic knowledge than non-strategic knowledge, but only when agents are able to punish. Copyright © 2012 Cognitive Science Society, Inc.

  12. 2015 Enterprise Strategic Vision

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

    None

    2015-08-01

    This document aligns with the Department of Energy Strategic Plan for 2014-2018 and provides a framework for integrating our missions and direction for pursuing DOE’s strategic goals. The vision is a guide to advancing world-class science and engineering, supporting our people, modernizing our infrastructure, and developing a management culture that operates a safe and secure enterprise in an efficient manner.

  13. Enhancing the Strategic Capability of the Army: An Investigation of Strategic Thinking Tasks, Skills, and Development

    DTIC Science & Technology

    2016-02-01

    continually develop their ability to think strategically, they gain the power to explore all options and help “ write the rules of the game” rather than...continually develop their ability to think strategically, they gain the power to explore all options and help “ write the rules of the game,” rather than...barriers to streamline communication Convey the position of multiple distinct agencies in writing through strategic use of language to the President

  14. Strategic planning: getting from here to there.

    PubMed

    Kaleba, Richard

    2006-11-01

    Hospitals should develop a strategic plan that defines specific actions in a realistic time frame. Hospitals can follow a five-phase process to develop a strategic plan. The strategic planning process requires a project leader and medical staff buy-in.

  15. 2014 Strategic Sustainability Performance Plan

    DTIC Science & Technology

    2014-06-30

    Strategic Sourcing Initiatives, such as Blanket Purchase Agreements ( BPAs ) for office products and imaging equipment, which include sustainable...end of FY2014. Use Federal Strategic Sourcing Initiatives, such as Blanket Purchase Agreements ( BPAs ) Yes USACE is required to participate in

  16. The Science of Strategic Communication

    EPA Science Inventory

    The field of Strategic Communication involves a focused effort to identify, develop, and present multiple types of communication media on a given subject. A Strategic Communication program recognizes the limitations of the most common communication models (primarily “one s...

  17. Hospital boards and hospital strategic focus: the impact of board involvement in strategic decision making.

    PubMed

    Ford-Eickhoff, Karen; Plowman, Donde Ashmos; McDaniel, Reuben R

    2011-01-01

    Despite pressures to change the role of hospital boards, hospitals have made few changes in board composition or director selection criteria. Hospital boards have often continued to operate in their traditional roles as either "monitors" or "advisors." More attention to the direct involvement of hospital boards in the strategic decision-making process of the organizations they serve, the timing and circumstances under which board involvement occurs, and the board composition that enhances their abilities to participate fully is needed. We investigated the relationship between broader expertise among hospital board members, board involvement in the stages of strategic decision making, and the hospital's strategic focus. We surveyed top management team members of 72 nonacademic hospitals to explore the participation of critical stakeholder groups such as the board of directors in the strategic decision-making process. We used hierarchical regression analysis to explore our hypotheses that there is a relationship between both the nature and involvement of the board and the hospital's strategic orientation. Hospitals with broader expertise on their boards reported an external focus. For some of their externally-oriented goals, hospitals also reported that their boards were involved earlier in the stages of decision making. In light of the complex and dynamic environment of hospitals today, those charged with developing hospital boards should match the variety in the external issues that the hospital faces with more variety in board makeup. By developing a board with greater breadth of expertise, the hospital responds to its complex environment by absorbing that complexity, enabling a greater potential for sensemaking and learning. Rather than acting only as monitors and advisors, boards impact their hospitals' strategic focus through their participation in the strategic decision-making process.

  18. Setting Strategic Directions Using Critical Success Factors.

    ERIC Educational Resources Information Center

    Bourne, Bonnie; Gates, Larry; Cofer, James

    2000-01-01

    Describes implementation of a system-level planning model focused on institutional improvement and effectiveness at the University of Missouri. Details implementation of three phases of the strategic planning model (strategic analysis, strategic thinking/decision-making, and campus outreach/systems administration planning); identifies critical…

  19. Strategic Management or Strategic Planning for Defense?

    DTIC Science & Technology

    1989-02-01

    manage at the regional or CinC level with an appreciation of strategic planning and management concepts currently taught at business schools . Military...those not in uniform. Science, engineering, and business schools all suggest that their faculties have experience tours so that they can appreciate

  20. Strategic planning for marketers.

    PubMed

    Wilson, I

    1978-12-01

    The merits of strategic planning as a marketing tool are discussed in this article which takes the view that although marketers claim to be future-oriented, they focus too little attention on long-term planning and forecasting. Strategic planning, as defined by these authors, usually encompasses periods of between five and twenty-five years and places less emphasis on the past as an absolute predictor of the future. It takes a more probabilistic view of the future than conventional marketing strategy and looks at the corporation as but one component interacting with the total environment. Inputs are examined in terms of environmental, social, political, technological and economic importance. Because of its futuristic orientation, an important tenant of strategic planning is the preparation of several alternative scenarios ranging from most to least likely. By planning for a wide-range of future market conditions, a corporation is more able to be flexible by anticipating the course of future events, and is less likely to become a captive reactor--as the authors believe is now the case. An example of strategic planning at General Elecric is cited.

  1. Excision of a viral reprogramming cassette by delivery of synthetic Cre mRNA

    PubMed Central

    Loh, Yuin-Han; Yang, Jimmy Chen; De Los Angeles, Alejandro; Guo, Chunguang; Cherry, Anne; Rossi, Derrick J.; Park, In-Hyun; Daley, George Q.

    2012-01-01

    The generation of patient-specific induced pluripotent stem (iPS) cells provides an invaluable resource for cell therapy, in vitro modeling of human disease, and drug screening. To date, most human iPS cells have been generated with integrating retro- and lenti-viruses and are limited in their potential utility because residual transgene expression may alter their differentiation potential or induce malignant transformation. Alternatively, transgene-free methods using adenovirus and protein transduction are limited by low efficiency. This report describes a protocol for the generation of transgene-free human induced pluripotent stem cells using retroviral transfection of a single vector, which includes the coding sequences of human OCT4, SOX2, KLF4, and cMYC linked with picornaviral 2A plasmids. Moreover, after reprogramming has been achieved, this cassette can be removed using mRNA transfection of Cre recombinase. The method described herein to excise reprogramming factors with ease and efficiency facilitates the experimental generation and use of transgene-free human iPS cells. PMID:22605648

  2. Strategic planning processes and hospital financial performance.

    PubMed

    Kaissi, Amer A; Begun, James W

    2008-01-01

    Many common management practices in healthcare organizations, including the practice of strategic planning, have not been subject to widespread assessment through empirical research. If management practice is to be evidence-based, evaluations of such common practices need to be undertaken. The purpose of this research is to provide evidence on the extent of strategic planning practices and the association between hospital strategic planning processes and financial performance. In 2006, we surveyed a sample of 138 chief executive officers (CEOs) of hospitals in the state of Texas about strategic planning in their organizations and collected financial information on the hospitals for 2003. Among the sample hospitals, 87 percent reported having a strategic plan, and most reported that they followed a variety of common practices recommended for strategic planning-having a comprehensive plan, involving physicians, involving the board, and implementing the plan. About one-half of the hospitals assigned responsibility for the plan to the CEO. We tested the association between these planning characteristics in 2006 and two measures of financial performance for 2003. Three dimensions of the strategic planning process--having a strategic plan, assigning the CEO responsibility for the plan, and involving the board--are positively associated with earlier financial performance. Further longitudinal studies are needed to evaluate the cause-and-effect relationship between planning and performance.

  3. Installation Strategic Planning Guidebook

    DTIC Science & Technology

    2012-05-01

    Installation natural resource concerns (for example, wetlands , number of endangered species, water use restrictions, encroachment on training lands...Koehler Publishing, 1994 7. Strategy Safari – A Guided Tour Through the Wilds of Strategic Management by Henry Mintzberg, Bruce Ahlstrand, and...T. (1987). NY: Knopf 36. Shaping Strategic Planning: Frogs, Dragons, Bees and Turkey Tails. Pfeiffer, J. W., Goodstein, L. D. & Nolan, T. M. (1989

  4. Alternative World Scenarios for Strategic Planning

    DTIC Science & Technology

    1988-01-20

    STRATEGIC STUDIES INSTITUTE U.S. ARMY WAR COLLEGE CARLISLE BARRACKS, PENNSYLVANIA 17013-5050 20 JANUARY 198 ACN 81001 Lfl 0ALTERNATIVE WORLD...Howard D. Graves STRATEGIC STUDIES INSTITUTE Director Colonel Thomas R. Stone Author Charles W. Tayloi Editor Marianne P. Cowling Secretary Shirley A...Shearer STRATEGIC STUDIES INSTITUTE U.S. ARMY WAR COLLEGE Carlisle Barracks, Pennsylvania 17013-5050 20 January 1988 ACN 88001 4e 4’ ALTERNATIVE

  5. Asymmetry in Children's Comprehension of Raising

    ERIC Educational Resources Information Center

    Choe, Jinsun; O'Grady, William

    2017-01-01

    This paper investigates English-speaking children's acquisition of raising constructions (e.g. "John seems to Mary to be happy") and fnds an asymmetric effect of NP type on their comprehension: an improvement in performance is observed when a lexical NP is raised across a pronominal experiencer (e.g. "John seems to her to be…

  6. JMJD3 Is Crucial for the Female AVPV RIP-Cre Neuron-Controlled Kisspeptin-Estrogen Feedback Loop and Reproductive Function.

    PubMed

    Song, Anying; Jiang, Shujun; Wang, Qinghua; Zou, Jianghuan; Lin, Zhaoyu; Gao, Xiang

    2017-06-01

    The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. Although most studies have focused on the hierarchy from the brain to the gonad, many questions remain unresolved concerning the feedback from the gonad to the central nervous system, especially regarding the potential epigenetic modifications in hypothalamic neurons. In the present report, we generated genetically modified mice lacking histone H3 lysine 27 (H3K27) demethylase Jumonji domain-containing 3 (JMJD3) in hypothalamic rat-insulin-promoter-expressing neurons (RIP-Cre neurons). The female mutant mice displayed late-onset obesity owing to reduced locomotor activity and decreased energy expenditure. JMJD3 deficiency in RIP-Cre neurons also results in delayed pubertal onset, an irregular estrous cycle, impaired fertility, and accelerated ovarian failure in female mice owing to the dysregulation of the hypothalamic-ovarian axis. We found that JMJD3 directly regulates Kiss1 gene expression by binding to the Kiss1 promoter and triggering H3K27me3 demethylation in the anteroventral periventricular (AVPV) nucleus. Further study confirmed that the aberrations arose from impaired kisspeptin signaling in the hypothalamic AVPV nucleus and subsequent estrogen deficiency. Estrogen replacement therapy can reverse obesity in mutant mice. Moreover, we demonstrated that Jmjd3 is an estrogen target gene in the hypothalamus. These results provide direct genetic and molecular evidence that JMJD3 is a key mediator for the kisspeptin-estrogen feedback loop. Copyright © 2017 Endocrine Society.

  7. Strategic Planning and Information Systems.

    ERIC Educational Resources Information Center

    Shuman, Jack N.

    1982-01-01

    Discusses the functions of business planning systems and analyzes the underlying assumptions of the information systems that support strategic planning efforts within organizations. Development of a system framework, obstacles to the successful creation of strategic planning information systems, and resource allocation in organizations are…

  8. A strategic plan to accelerate development of acute stroke treatments.

    PubMed

    Marler, John R

    2012-09-01

    In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care. © 2012 New York Academy of Sciences.

  9. Strategic planning--the role of the chief executive.

    PubMed

    Daniel, A L

    1992-04-01

    Failure to see strategic planning as a process and ineffective CEO involvement are two reasons for failures in strategic planning. This article outlines the stages in an effective strategic planning process, discusses the appropriate role or roles for the CEO or leader in each stage, and defines the expected results from effective strategic planning.

  10. The Value of Strategic Partnerships

    ScienceCinema

    Gould, Josh; Narayan, Amit; McNutt, Ty

    2018-05-30

    Strong strategic partnerships can be the difference between those technologies that only achieve success in the lab and those that actually break into the marketplace. Two ARPA-E awardees—AutoGrid and APEI—have forged strategic partnerships that have positioned their technologies to achieve major success in the market. This video features remarks from ARPA-E Technology-to-Market Advisor Josh Gould and interviews with technologists at AutoGrid and APEI, who each tell the story of how their company leveraged relationships with strategic partners to broaden their customer base and bring their technology to life.

  11. Rethinking Strategy and Strategic Leadership in Schools.

    ERIC Educational Resources Information Center

    Davies, Brent

    2003-01-01

    Reviews nature of strategy and strategic leadership in schools. Considers how leaders can map and reconceptualize the nature of strategy and develop strategic capabilities for longer-term sustainability. Questions hierarchical models of leadership. Highlights three characteristics of strategically oriented schools; suggests ways to improve art of…

  12. Strategic Planning for School Administrators. Fastback 457.

    ERIC Educational Resources Information Center

    Prosise, Roger

    This fastback document examines the strategic-planning process. Intended for school administrators, the booklet offers practical advice on strategic planning, and the importance of such planning in those districts that experience high turnover. When conceptualizing a strategic plan, administrators should begin with an end in mind and then develop…

  13. Strategic Planning for Higher Education.

    ERIC Educational Resources Information Center

    Kotler, Philip; Murphy, Patrick E.

    1981-01-01

    The framework necessary for achieving a strategic planning posture in higher education is outlined. The most important benefit of strategic planning for higher education decision makers is that it forces them to undertake a more market-oriented and systematic approach to long- range planning. (Author/MLW)

  14. Strategic Marketing for Educational Systems.

    ERIC Educational Resources Information Center

    Hanson, E. Mark; Henry, Walter

    1992-01-01

    Private-sector strategic marketing processes can significantly benefit schools desiring to develop public confidence and support and establish guidelines for future development. This article defines a strategic marketing model for school systems and articulates the sequence of related research and operational steps comprising it. Although schools…

  15. Raising Responsible Teenagers.

    ERIC Educational Resources Information Center

    Myers, Bob

    Some parents raise children without knowing anything about child development and are thus bewildered about how to deal with difficult behavior. This books addresses three important areas of parenting--child development, parenting style, and discipline--and tries to help parents gain the self-control needed to become competent adults. Chapters 1,…

  16. Enhancing a College's Fund-Raising Ability. ERIC Digest.

    ERIC Educational Resources Information Center

    Leslie, Larry L.

    Suggestions on how to enhance a college's fund-raising abilities are presented. Six sections are as follows: exemplary performers (noting the relationships between amounts raised and strategies employed); what works and what does not work in fund- raising (an institution's public visibility is important, and a poverty strategy is not); whether…

  17. 5 CFR 2421.21 - Affected by issues raised.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Affected by issues raised. 2421.21 Section 2421.21 Administrative Personnel FEDERAL LABOR RELATIONS AUTHORITY, GENERAL COUNSEL OF THE FEDERAL... § 2421.21 Affected by issues raised. The phrase affected by issues raised, as used in part 2422, should...

  18. Children’s strategic theory of mind

    PubMed Central

    Sher, Itai; Koenig, Melissa; Rustichini, Aldo

    2014-01-01

    Human strategic interaction requires reasoning about other people’s behavior and mental states, combined with an understanding of their incentives. However, the ontogenic development of strategic reasoning is not well understood: At what age do we show a capacity for sophisticated play in social interactions? Several lines of inquiry suggest an important role for recursive thinking (RT) and theory of mind (ToM), but these capacities leave out the strategic element. We posit a strategic theory of mind (SToM) integrating ToM and RT with reasoning about incentives of all players. We investigated SToM in 3- to 9-y-old children and adults in two games that represent prevalent aspects of social interaction. Children anticipate deceptive and competitive moves from the other player and play both games in a strategically sophisticated manner by 7 y of age. One game has a pure strategy Nash equilibrium: In this game, children achieve equilibrium play by the age of 7 y on the first move. In the other game, with a single mixed-strategy equilibrium, children’s behavior moved toward the equilibrium with experience. These two results also correspond to two ways in which children’s behavior resembles adult behavior in the same games. In both games, children’s behavior becomes more strategically sophisticated with age on the first move. Beyond the age of 7 y, children begin to think about strategic interaction not myopically, but in a farsighted way, possibly with a view to cooperating and capitalizing on mutual gains in long-run relationships. PMID:25197065

  19. Immunologic applications of conditional gene modification technology in the mouse.

    PubMed

    Sharma, Suveena; Zhu, Jinfang

    2014-04-02

    Since the success of homologous recombination in altering mouse genome and the discovery of Cre-loxP system, the combination of these two breakthroughs has created important applications for studying the immune system in the mouse. Here, we briefly summarize the general principles of this technology and its applications in studying immune cell development and responses; such implications include conditional gene knockout and inducible and/or tissue-specific gene over-expression, as well as lineage fate mapping. We then discuss the pros and cons of a few commonly used Cre-expressing mouse lines for studying lymphocyte development and functions. We also raise several general issues, such as efficiency of gene deletion, leaky activity of Cre, and Cre toxicity, all of which may have profound impacts on data interpretation. Finally, we selectively list some useful links to the Web sites as valuable mouse resources. Copyright © 2014 John Wiley & Sons, Inc.

  20. 7 CFR 760.211 - Farm-raised fish payment calculations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Farm-raised fish payment calculations. 760.211 Section..., Honeybees, and Farm-Raised Fish Program § 760.211 Farm-raised fish payment calculations. (a) An eligible farm-raised fish producer may receive payments for fish feed losses due to an eligible adverse weather...

  1. 7 CFR 760.211 - Farm-raised fish payment calculations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Farm-raised fish payment calculations. 760.211 Section..., Honeybees, and Farm-Raised Fish Program § 760.211 Farm-raised fish payment calculations. (a) An eligible farm-raised fish producer may receive payments for fish feed losses due to an eligible adverse weather...

  2. 7 CFR 760.211 - Farm-raised fish payment calculations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Farm-raised fish payment calculations. 760.211 Section..., Honeybees, and Farm-Raised Fish Program § 760.211 Farm-raised fish payment calculations. (a) An eligible farm-raised fish producer may receive payments for fish feed losses due to an eligible adverse weather...

  3. 7 CFR 760.211 - Farm-raised fish payment calculations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Farm-raised fish payment calculations. 760.211 Section..., Honeybees, and Farm-Raised Fish Program § 760.211 Farm-raised fish payment calculations. (a) An eligible farm-raised fish producer may receive payments for fish feed losses due to an eligible adverse weather...

  4. 7 CFR 760.211 - Farm-raised fish payment calculations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Farm-raised fish payment calculations. 760.211 Section..., Honeybees, and Farm-Raised Fish Program § 760.211 Farm-raised fish payment calculations. (a) An eligible farm-raised fish producer may receive payments for fish feed losses due to an eligible adverse weather...

  5. USAF Strategic Master Plan

    DTIC Science & Technology

    2015-05-01

    objectives, and four annexes: the Human Capital Annex ( HCA ), Strategic Posture Annex (SPA), Capabilities Annex (CA), and the Science and Technology...translate the SMP’s comprehensive goals and objectives into tangible actions and priorities. The four annexes are as follows:  Human Capital Annex ( HCA ...Figure 1: Internal Structure of the SMP Through the HCA , SPA, CA, and STA, the SMP consolidates and transmits strategic direction to staffs

  6. Strategic Activism, Educational Leadership and Social Justice

    ERIC Educational Resources Information Center

    Ryan, James

    2016-01-01

    This article describes the strategic activism of educational leaders who promote social justice. Given the risks, educational leaders need to be strategic about the ways in which they pursue their activism. Citing current research, this article explores the ways in which leaders strategically pursue their social justice agendas within their own…

  7. National Weather Service - Strategic Planning and Policy

    Science.gov Websites

    Service Select to go to the NWS homepage Strategic Planning and Policy Site Map News Organization Search button to submit request City, St Go Homepage - Strategic Planning and Policy NWS Strategic Plan Current Plan Archive Policy Issues Public/Private Data Rights International Data Presentations/Tools

  8. o,p'-DDT induces cyclooxygenase-2 gene expression in murine macrophages: Role of AP-1 and CRE promoter elements and PI3-kinase/Akt/MAPK signaling pathways

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

    Han, Eun Hee; Kim, Ji Young; Kim, Hyung-Kyun

    Dichlorodiphenyltrichloroethane (DDT) has been used as an insecticide to prevent the devastation of malaria in tropical zones. However, many reports suggest that DDT may act as an endocrine disruptor and may have possible carcinogenic effects. Cyclooxygenase-2 (COX-2) acts as a link between inflammation and carcinogenesis through its involvement in tumor promotion. In the present study, we examined the effect of o,p'-DDT on COX-2 gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. Exposure to o,p'-DDT markedly enhanced the production of prostaglandin E{sub 2} (PGE{sub 2}), a major COX-2 metabolite, in murine macrophages. Furthermore, o,p'-DDTmore » dose-dependently increased the levels of COX-2 protein and mRNA. Transfection with human COX-2 promoter construct, electrophoretic mobility shift assays and DNA-affinity protein-binding assay experiments revealed that o,p'-DDT activated the activator protein 1 (AP-1) and cyclic AMP response element (CRE) sites, but not the NF-{kappa}B site. Phosphatidylinositol 3 (PI3)-kinase, its downstream signaling molecule, Akt, and mitogen-activated protein kinases (MAPK) were also significantly activated by the o,p'-DDT-induced AP-1 and CRE activation. These results demonstrate that o,p'-DDT induced COX-2 expression via AP-1 and CRE activation through the PI3-K/Akt/ERK, JNK, and p38 MAP kinase pathways. These findings provide further insight into the signal transduction pathways involved in the carcinogenic effects of o,p'-DDT.« less

  9. Transformational Assessment: A Simplified Model of Strategic Planning

    ERIC Educational Resources Information Center

    Bardwell, Rebecca

    2008-01-01

    Strategic planning is a way to evaluate a present situation and set a course for the future. While there is no dearth of literature on Strategic Planning, there appears to be reluctance on the part of K-12 educators to engage in strategic planning. Besides the cynicism about change, another roadblock to strategic planning is the time it takes.…

  10. The Ethics of Strategic Ambiguity.

    ERIC Educational Resources Information Center

    Paul, Jim; Strbiak, Christy A.

    1997-01-01

    Examines the concept of strategic ambiguity in communication, and addresses the ethics of strategic ambiguity from an intrapersonal perspective that considers the congruity of communicators' espoused-ethics, ethics-in-use, and behavior, where ethical judgements are based on the congruity between espoused-ethics and actual behavior. Poses questions…

  11. Strategic Human Resource Development. Symposium.

    ERIC Educational Resources Information Center

    2002

    This document contains three papers on strategic human resource (HR) development. "Strategic HR Orientation and Firm Performance in India" (Kuldeep Singh) reports findings from a study of Indian business executives that suggests there is a positive link between HR policies and practices and workforce motivation and loyalty and…

  12. NASA Space Sciences Strategic Planning

    NASA Technical Reports Server (NTRS)

    Crane, Philippe

    2004-01-01

    The purpose of strategic planning roadmap is to:Fulfill the strategic planning requirements; Provide a guide to the science community in presenting research requests to NASA; Inform and inspire; Focus investments in technology and research for future missions; and Provide the scientific and technical justification for augmentation requests.

  13. CRE dating on the scarps of large landslides affecting the Belledonne massif ( French Alps)

    NASA Astrophysics Data System (ADS)

    Lebrouc, V.; Baillet, L.; Schwartz, S.; Jongmans, D.; Gamond, J. F.; Bourles, D.; Le Roux, O.; Carcaillet, J.; Braucher, R.

    2012-04-01

    The southwestern edge of the Belledonne Massif (French Alps) consists of micaschists unconformably covered with Mesozoic sediments and Quaternary deposits. The morphology corresponds to a glacial plateau (Mont Sec plateau) bordered by steep slopes (around 40°), where moraines and peat bog subsist. The massif is incised by the East-West trending Romanche valley that was shaped by several cycles of quaternary glaciations and deglaciations. Slopes are affected by several active or past large scale rock mass instabilities. Cosmic Ray Exposure (CRE) dating was applied on the head scarps of three large landslides, one of which being the active Séchilienne landslide whose headscarp was already dated by Leroux et al. [2009]. Dating results suggest a concomitant initiation of these instabilities at about 7 ± 2 10Be ka, thousands years after the total downwastage of the valley. A different kinematic behaviour was however observed on two contiguous landslides for which continuous exposure profiles were obtained. On the Séchilienne landslide, 23 samples were collected from internal and lateral scarps, as well as on polished bedrock surfaces, with the aim of dating the internal kinematics of the landslide. Preliminary dating results obtained on polished surfaces and near the top of the scarps show unexpected low 10Be concentrations, suggesting the existence of thin moraine or peat bog deposits masking the bedrock, which have been subsequently eroded. The minimum thickness of these deposits was estimated assuming a constant denudation rate over time. Exposure date profiles show that the studied lateral and internal scarps were initiated at the same period as the Sechilienne headscarp. An increase in the exposure rate was also observed between 2 and 1 ka, in agreement with that evidenced along the headscarp. Forty other samples have been collected in the landslide to corroborate these results. Reference Le Roux, O., S. Schwartz , J.-F. Gamond, D. Jongmans, D. Bourles, R

  14. Raising Sensitive Issues in a Team

    ERIC Educational Resources Information Center

    Lindoerfer, Dennis

    2008-01-01

    Have you ever wondered how to deal with a sensitive issue within your team? For example, how do you raise the issue that the women rarely get listened to? How do you bring up your observation that the team members from Marketing always dominate the meetings? This guidebook focuses on ways to determine whether to raise such an issue in a team…

  15. A Strategic Plan Is Just the Beginning

    ERIC Educational Resources Information Center

    Wilson, E. B.

    2009-01-01

    The process of strategic planning wears out institutions. Strategic planning, pursued with high purpose and energy, is enervating and exhausting. In this article, the author describes the value-added work of trustees in high-performing boards and discusses the role boards of trustees play as the process of continuous strategic planning unfolds.…

  16. What is strategic management?

    PubMed

    Jasper, Melanie; Crossan, Frank

    2012-10-01

    To discuss the theoretical concept of strategic management and explore its relevance for healthcare organisations and nursing management. Despite being a relatively new approach, the growth of strategic management within organisations has been consistently and increasingly promoted. However, comprehensive definitions are scarce and commonalities of interpretation are limited. This paper presents an exploratory discussion of the construct of strategic management, drawing on the literature and questioning its relevance within health-care organisations. Literature relating to strategic management across a number of fields was accessed, drawing primarily on meta-studies within management literature, to identify key concepts and attempt to present a consistent definition. The concept within health care is explored in relation to nursing management. Inconsistency in definitions and utilisation of key concepts within this management approach results in the term being loosely applied in health-care organisations without recourse to foundational principles and a deep understanding of the approach as a theory as opposed to an applied term. Nurse managers are increasingly asked to adopt the 'next-best-thing' in managerial theories, yet caution needs to be taken in nurses agreeing to use systems that lack an evidence base in terms of both efficacy and relevance of context. © 2012 Blackwell Publishing Ltd.

  17. Excellence in Educational Fund Raising at America's Community Colleges and a Key Resources Guide for Educational Fund Raising.

    ERIC Educational Resources Information Center

    Ryan, G. Jeremiah

    Designed to encourage and inform community college efforts to secure private financial support, this literature review and resource guide examine the current status of fund raising at community colleges and list pertinent information sources. After introductory comments advocate increased community college involvement in fund raising, the paper…

  18. Strategic Planning and Online Learning

    ERIC Educational Resources Information Center

    McLaughlin-Graham, Karen; Berge, Zane L.

    2005-01-01

    Strategic planning is a critical part of sustaining distance education. Through such planning, the organization can solve business problems that involve training and education in an effective and often cost savings manner compared to in-person training efforts. This paper examines the strategic planning process as it relates to sustaining distance…

  19. Strategic business planning linking strategy with financial reality.

    PubMed

    Bachrodt, Andrew K; Smyth, J Patrick

    2004-11-01

    To succeed in today's complex and often adverse business environment, a healthcare organization's strategic direction must be calculated, focused, and financially sustainable. Strategic business planning is an essential tool to help organizations focus strategic choices within the financial realities of their environment. An effective strategic business planning cycle includes conducting an assessment, identifying business objectives, developing strategy, conducting an impact analysis, and developing an implementation plan.

  20. The French Strategic Dilemma.

    DTIC Science & Technology

    1984-03-01

    THE FRENCH STRATEGIC DILEMMA This paper identifies a basic strategic dilemma for France . On the one hand, French leaders identify the political purpose...are inducing a need for France to provide a more explicit definition of the role of French nuclear weapons in the West European security system. In...defense policy in France . This section concludes with an assessment of the alternative scenarios for the evolution of French defense policy in the 1980s

  1. Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP.

    PubMed

    Bi, Yanzhen; Hua, Zaidong; Liu, Ximei; Hua, Wenjun; Ren, Hongyan; Xiao, Hongwei; Zhang, Liping; Li, Li; Wang, Zhirui; Laible, Götz; Wang, Yan; Dong, Faming; Zheng, Xinmin

    2016-08-17

    Predictable, clean genetic modification (GM) in livestock is important for reliable phenotyping and biosafety. Here we reported the generation of isozygous, functional myostatin (MSTN) knockout cloned pigs free of selectable marker gene (SMG) by CRISPR/Cas9 and Cre/LoxP. CRISPR/Cas9-mediated homologous recombination (HR) was exploited to knock out (KO) one allele of MSTN in pig primary cells. Cre recombinase was then used to excise the SMG with an efficiency of 82.7%. The SMG-free non-EGFP cells were isolated by flow cytometery and immediately used as donor nuclei for nuclear transfer. A total of 685 reconstructed embryos were transferred into three surrogates with one delivering two male live piglets. Molecular testing verified the mono-allelic MSTN KO and SMG deletion in these cloned pigs. Western blots showed approximately 50% decrease in MSTN and concurrent increased expression of myogenic genes in muscle. Histological examination revealed the enhanced myofiber quantity but myofiber size remained unaltered. Ultrasonic detection showed the increased longissimus muscle size and decreased backfat thickness. Precision editing of pig MSTN gene has generated isozygous, SMG-free MSTN KO cloned founders, which guaranteed a reliable route for elite livestock production and a strategy to minimize potential biological risks.

  2. A Primer on Strategic Financial Assessments.

    ERIC Educational Resources Information Center

    Richman, Naomi; Fitzgerald, Susan

    2003-01-01

    Describes how to perform a strategic financial assessment to enable the board to understand the fundamental internal and external challenges and opportunities confronting the institution when decision making and strategic capital planning. (EV)

  3. 12 CFR 563e.27 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Strategic plan. 563e.27 Section 563e.27 Banks... for Assessing Performance § 563e.27 Strategic plan. (a) Alternative election. The OTS will assess a... strategic plan if: (1) The savings association has submitted the plan to the OTS as provided for in this...

  4. Promise or Peril: The Strategic Defense Initiative.

    ERIC Educational Resources Information Center

    Brzezinski, Zbigniew, Ed.; And Others

    The major policy debate touched off by President Reagan's March 1983 speech announcing the Strategic Defense Initiative (SDI) was the reopening of one that had begun 35 years before. Then and now the ultimate question is what kind of strategic posture is most likely to contribute to mutual strategic stability? The answer is central to national…

  5. 50 CFR 14.23 - Live farm-raised fish and farm-raised fish eggs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF WILDLIFE AND PLANTS IMPORTATION, EXPORTATION, AND TRANSPORTATION OF WILDLIFE Importation and... and farm-raised fish eggs meet the definition of “bred in captivity” as stated in 50 CFR 17.3. Except...

  6. A Strategic Culture Assessment of the Transatlantic Divide

    DTIC Science & Technology

    2008-03-01

    security divide through the strategic culture lens, taking a comparative case study approach . It analyzes the emergent EU strategic culture by looking...utilize the strategic culture approach in the ensuing case study comparisons. B. WHY THE USE OF STRATEGIC CULTURE? In a study published in 2004...analysis use a comparative cultural approach when a previous comparison of U.S. and EU behavior found these actors’ behavior most aligned with realism’s

  7. Hospital strategic preparedness planning: the new imperative.

    PubMed

    Ginter, Peter M; Duncan, W Jack; Abdolrasulnia, Maziar

    2007-01-01

    Strategic preparedness planning is an important new imperative for many hospitals. Strategic preparedness planning goes beyond traditional product/market strategic planning by focusing on disaster prevention, containment, and response roles. Hospitals, because of their unique mission, size, complexity, the types of materials they handle, and the types of patients they encounter, are especially vulnerable to natural and human-initiated disasters. In addition, when disasters occur, hospitals must develop well-conceived first responder (receiver) strategies. This paper argues the case for strategic preparedness planning for hospitals and proposes a process for this relatively new and much needed type of planning.

  8. Strategic Planning Is an Oxymoron

    ERIC Educational Resources Information Center

    Bassett, Patrick F.

    2012-01-01

    The thinking on "strategic thinking" has evolved significantly over the years. In the previous century, the independent school strategy was to focus on long-range planning, blithely projecting 10 years into the future. For decades this worked well enough, but in the late 20th century, independent schools shifted to "strategic planning," with its…

  9. 77 FR 25706 - Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ..., Command and Control, Science and Technology, Missile Defense. Meeting Accessibility: Pursuant to 5 U.S.C... DEPARTMENT OF DEFENSE Notice of Advisory Committee Closed Meeting; U.S. Strategic Command Strategic Advisory Group AGENCY: Department of Defense. ACTION: Notice of Advisory Committee closed meeting...

  10. Strategic Purchasing in Practice: Comparing Ten European Countries.

    PubMed

    Klasa, Katarzyna; Greer, Scott L; van Ginneken, Ewout

    2018-02-05

    Strategic purchasing of health care services is widely recommended as a policy instrument. We conducted a review of literature of material drawn from the European Observatory on Health Systems and Policies Health Systems in Transition series, other European Observatory databases, and selected country-specific literature to augment the comparative analysis by providing the most recent healthcare trends in ten selected countries. There is little evidence of purchasing being strategic according to any of the established definitions. There is little or no literature suggesting that existing purchasing mechanisms in Europe deliver improved population health, citizen empowerment, stronger governance and stewardship, or develop purchaser organization and capacity. Strategic purchasing has not generally been implemented. Policymakers considering adopting strategic purchasing policies should be aware of this systemic implementation problem. Policymakers in systems with strategic purchasing built into policy should not assume that a purchasing system is strategic or that it is delivering any expected objectives. However, there are individual components of strategic purchasing that are worth pursuing and can provide benefits to health systems. Copyright © 2018. Published by Elsevier B.V.

  11. Thinking strategically about capitation.

    PubMed

    Boland, P

    1997-05-01

    All managed care stakeholders--health plan members, employers, providers, community organizations, and government entitites--share a common interest in reducing healthcare costs while improving the quality of care health plan members receive. Although capitation is a usually thought of primarily as a payment mechanism, it can be a powerful tool providers and health plans can use to accomplish these strategic objectives and others, such as restoring and maintaining the health of plan members or improving a community's health status. For capitation to work effectively as a strategic tool, its use must be tied to a corporate agenda of partnering with stakeholders to achieve broader strategic goals. Health plans and providers must develop a partnership strategy in which each stakeholder has well-defined roles and responsibilities. The capitation structure must reinforce interdependence, shift focus from meeting organizational needs to meeting customer needs, and develop risk-driven care strategies.

  12. Fund Raising with Panache.

    ERIC Educational Resources Information Center

    Dedman, Robert

    1985-01-01

    The key to fund raising is the donor, and fund raisers should learn to cultivate potential donors, approach them with goals compatible with their own, supplement their thinking, get them involved, and swamp them with gratitude. (MSE)

  13. An Exploration of Strategic Planning Perspectives and Processes within Community Colleges Identified as Being Distinctive in Their Strategic Planning Practices

    ERIC Educational Resources Information Center

    Augustyniak, Lisa J.

    2015-01-01

    Community college leaders face unprecedented change, and some have begun reexamining their institutional strategic planning processes. Yet, studies in higher education strategic planning spend little time examining how community colleges formulate their strategic plans. This mixed-method qualitative study used an expert sampling method to identify…

  14. United States Strategic Plan for International Affairs.

    DTIC Science & Technology

    1998-01-01

    Humanitarian Response 39 Global Issues 41 US Strategic Plan for International Affairs International Affairs Strategic Plan Summary and Introduction...minimize the human costs of conflict and natural disasters. Global Issues : • Secure a sustainable global environment in order to protect the United States...involvement in addressing crises. 40 US Strategic Plan for International Affairs NATIONAL INTEREST: Global Issues The global environment has a

  15. Microgravity strategic planning exercise

    NASA Technical Reports Server (NTRS)

    Halpern, Richard; Downey, Jim; Harvey, Harold

    1991-01-01

    The Center for Space and Advanced Technology supported a planning exercise for the Microgravity Program management at the Marshall Space Flight Center. The effort focused on the status of microgravity work at MSFC and elsewhere with the objective of preparing a goal-oriented strategic planning document which could be used for informational/brochure purposes. The effort entailed numerous interactions and presentations with Field Center programmatic components and Headquarters personnel. Appropriate material was consolidated in a draft format for a MSFC Strategic Plan.

  16. Surrogate mothers: aboriginal grandmothers raising grandchildren in Taiwan.

    PubMed

    Chang, Yu-Ting; Hayter, Mark

    2011-05-01

    The purpose of this qualitative study was to understand the experiences of Taiwanese aboriginal grandmothers when raising their grandchildren. Adopting a phenomenological approach, interviews were conducted with 15 Taiwanese aboriginal grandmothers who served as primary caregiver to a grandchild or grandchildren. Data were analyzed using Giorgi's phenomenological method. Four themes emerged from the data analysis, reflecting the parenting experience of grandmothers: using aged bodies to do energetic work: represented the physical effects of raising grandchildren; conflicting emotions: reflected the psychological effects of raising grandchildren; lifelong and privative obligation: described the cultural and societal beliefs of raising grandchildren; and coping strategies for raising grandchildren outlined methods the grandmothers used to cope with parenting their grandchildren. The results of this study offers insights into surrogate parenting within an underresearched group in Taiwan and will enable health care providers to be more aware of the physical, emotional, and social effects of the role of grandparent parenting.

  17. Theater gateway closure: a strategic level barricade

    DTIC Science & Technology

    that at the strategic level the effects are based on the economic and diplomatic elements of the national power, affecting proportionally sustainment...Seven months of detrimental political implications, expensive effects on military operations, and strategic level barricades during 2011 and 2012 in...logistical planners at the strategic level can anticipate or mitigate the effects of a theater gateway closure on military operations. Through two

  18. Metrics for NASA Aeronautics Research Mission Directorate (ARMD) Strategic Thrust 3B Vertical Lift Strategic Direction

    NASA Technical Reports Server (NTRS)

    Hochstetler, Ronald D.; Salvano, Dan; Gorton, Susan A.

    2017-01-01

    The NASA Aeronautics Research Mission Directorate (ARMD) Strategic Implementation Plan details an ambitious plan for aeronautical research for the next quarter century and beyond. It includes a number of advanced technologies needed to address requirements of the overall aviation community (domestic and international), with an emphasis on safety, efficiency, operational flexibility, and alternative propulsion air transport options. The six ARMD Strategic Thrust Areas (STAs) represent a specific set of multi-decade research agendas for creating the global aviation improvements most in demand by the aviation service consumers and the general public. To provide NASA with a measurement of the preeminent value of these research areas, it was necessary to identify and quantify the measurable benefits to the aviation community from capabilities delivered by the research programs. This paper will describe the processes used and the conclusions reached in defining the principal metrics for ARMD Strategic Thrust Area 3B "Vertical Lift Strategic Direction."

  19. Against Raising Hope of Raising the Dead: Contra Moody and Kubler-Ross.

    ERIC Educational Resources Information Center

    Vicchio, Stephen J.; And Others

    1979-01-01

    Kubler-Ross and Moody have made assertions about survival after death. They argued that the subjects were not dead, but in the process of dying. An alternative explanation to this "glimpse of the afterlife" approach is offered. Other theological objections are raised to the Moody/Kubler-Ross approach. (Author)

  20. Experiences that develop the ability to think strategically.

    PubMed

    Goldman, Ellen; Cahill, Terrence; Filho, Rubens Pessanha

    2009-01-01

    The ability to think strategically is an admired and a sought-after leadership requirement, yet we know little about how it develops. The purpose of this study is to identify specific experiences that contribute to the development of an individual's ability to think strategically. We identified eight work experiences, including different types of organizational projects, processes, and relationships, that contribute to an individual's strategic thinking ability. We also delineate specific characteristics material to each experience. These characteristics indicate that considerable time and focus are required to develop the ability to think strategically. In addition, the experiences are not all accessed equally: Women are less likely to have nonrelational experiences, while chief executive officers are more likely to have the most challenging ones. In addition, we found differences regarding work-related continuing education activities. Respondents rated nonhealthcare conferences and reading behind all other identified experiences that contribute to strategic thinking ability. Individuals can implement several strategies to improve their strategic thinking ability, including deliberately incorporating the requisite experiences into their development plans, ensuring that the experiences incorporate the required characteristics, and improving the benefit received from attending educational programs in nonhealthcare industries. Organizations can implement several strategies to ensure the experiences are as effective as possible, such as appraising gender differences across the experiences and reviewing the organization's strategic planning processes for the characteristics that best encourage strategic thinking.

  1. Children's Difficulty with Raising: A Performance Account

    ERIC Educational Resources Information Center

    Choe, Jinsun; Deen, Kamil

    2016-01-01

    This article explores English-speaking children's acquisition of raising structures with an experiencer (e.g.," John seems to Mary to be happy"). We review and address previously unnoticed issues in the methodologies of existing studies testing the acquisition of raising, thus providing a more reliable picture of children's abilities…

  2. Strategic Analysis of Terrorism

    NASA Astrophysics Data System (ADS)

    Arce, Daniel G.; Sandler, Todd

    Two areas that are increasingly studied in the game-theoretic literature on terrorism and counterterrorism are collective action and asymmetric information. One contribution of this chapter is a survey and extension of continuous policy models with differentiable payoff functions. In this way, policies can be characterized as strategic substitutes (e. g., proactive measures), or strategic complements (e. g., defensive measures). Mixed substitute-complement models are also introduced. We show that the efficiency of counterterror policy depends upon (i) the strategic substitutes-complements characterization, and (ii) who initiates the action. Surprisingly, in mixed-models the dichotomy between individual and collective action may disappear. A second contribution is the consideration of a signaling model where indiscriminant spectacular terrorist attacks may erode terrorists’ support among its constituency, and proactive government responses can create a backlash effect in favor of terrorists. A novel equilibrium of this model reflects the well-documented ineffectiveness of terrorism in achieving its stated goals.

  3. Characterization of a new Gsx2-cre line in the developing mouse telencephalon.

    PubMed

    Qin, Shenyue; Madhavan, Mayur; Waclaw, Ronald R; Nakafuku, Masato; Campbell, Kenneth

    2016-10-01

    In this study, we generated a transgenic mouse line driving Cre and EGFP expression with two putative cis-regulatory modules (CRMs) (i.e., hs687 and hs678) upstream of the homeobox gene Gsx2 (formerly Gsh2), a critical gene for establishing lateral ganglionic eminence (LGE) identity. The combination of these two CRMs drives transgene expression within the endogenous Gsx2 expression domains along the anterior-posterior neuraxis. By crossing this transgenic line with the Rosa tdTomato (Ai14) reporter mouse line, we observed a unique recombination pattern in the lateral ventral telencephalon, namely the LGE and the dorsal half of the medial GE (MGE), but not in the septum. We found robust recombination in many cell types derived from these embryonic regions, including olfactory bulb and amygdala interneurons and striatal projection neurons from the LGE, as well as cortical interneurons from the MGE and caudal GE (CGE). In summary, this transgenic mouse line represents a new tool for genetic manipulation in the LGE/CGE and the dorsal half of MGE. © 2016 Wiley Periodicals, Inc.

  4. Strategic Capability Development in the Higher Education Sector

    ERIC Educational Resources Information Center

    Brown, Paul

    2004-01-01

    The research adopts a case study approach (in higher education) to investigate how strategic capabilities might be developed in an organisation through strategic management development (SMD). SMD is defined as "Management development interventions which are intended to enhance the strategic capability and corporate performance of an…

  5. Verb-raising and Numeral Classifiers in Japanese: Incompatible Bedfellows.

    ERIC Educational Resources Information Center

    Fukushima, Kazuhiko

    2003-01-01

    Examines verb raising in Japanese and looks at Koizumi's (2000) evidence for verb-raising based on data involving, among other things, numeral classifiers. Demonstrates that Koizumi's evidence based on numeral classifiers does not support his claim that verb-raising occurs in Japanese. (Author/VWL)

  6. Strategic Leader Development for a 21st Century Army

    DTIC Science & Technology

    2008-04-30

    Fall of Strategic Planning. New York, NY: The Free Press, 1994. Northouse , Peter G. Leadership : Theory and Practice. Thousand Oaks, CA: Sage...TERMS Strategic Leadership ; Strategic Thinking; Contemporary Operational Environment; Adaptability; Self Awareness; Complexity; Officer Education...managing today’s fluid operational environment. The concept of strategic leadership , therefore, must be examined closely in Army doctrine. Social

  7. Transformation and Change Management for Strategic Leaders

    DTIC Science & Technology

    2002-04-09

    TRANSFORMATION AND CHANGE MANAGEMENT FOR STRATEGIC LEADERS BY MR. KENNETH L. WRIGHT Department of the Army DISTRIBUTION STATEMENT A: Approved for Public...PROJECT TRANSFORMATION AND CHANGE MANAGEMENT FOR STRATEGIC LEADERS BY MR. KENNETH L. WRIGHT DEPARTMENT OF THE ARMY Dr. Robert M. Murphy Project Advisor The...STRATEGIC LEADERS FORMAT: Strategy Research Project DATE: 09 April 2002 PAGES: 33 CLASSIFICATION: Unclassified The objective of this work is to examine

  8. A novel CBL-Bflox/flox mouse model allows tissue-selective fully conditional CBL/CBL-B double-knockout: CD4-Cre mediated CBL/CBL-B deletion occurs in both T-cells and hematopoietic stem cells

    PubMed Central

    Goetz, Benjamin; An, Wei; Mohapatra, Bhopal; Zutshi, Neha; Iseka, Fany; Storck, Matthew D.; Meza, Jane; Sheinin, Yuri; Band, Vimla; Band, Hamid

    2016-01-01

    CBL-family ubiquitin ligases are critical negative regulators of tyrosine kinase signaling, with a clear redundancy between CBL and CBL-B evident in the immune cell and hematopoietic stem cell studies. Since CBL and CBL-B are negative regulators of immune cell activation, elimination of their function to boost immune cell activities could be beneficial in tumor immunotherapy. However, mutations of CBL are associated with human leukemias, pointing to tumor suppressor roles of CBL proteins; hence, it is critical to assess the tumor-intrinsic roles of CBL and CBL-B in cancers. This has not been possible since the only available whole-body CBL-B knockout mice exhibit constitutive tumor rejection. We engineered a new CBL-Bflox/flox mouse, combined this with an existing CBLflox/flox mouse to generate CBLflox/flox; CBL-Bflox/flox mice, and tested the tissue-specific concurrent deletion of CBL and CBL-B using the widely-used CD4-Cre transgenic allele to produce a T-cell-specific double knockout. Altered T-cell development, constitutive peripheral T-cell activation, and a lethal multi-organ immune infiltration phenotype largely resembling the previous Lck-Cre driven floxed-CBL deletion on a CBL-B knockout background establish the usefulness of the new model for tissue-specific CBL/CBL-B deletion. Unexpectedly, CD4-Cre-induced deletion in a small fraction of hematopoietic stem cells led to expansion of certain non-T-cell lineages, suggesting caution in the use of CD4-Cre for T-cell-restricted gene deletion. The establishment of a new model of concurrent tissue-selective CBL/CBL-B deletion should allow a clear assessment of the tumor-intrinsic roles of CBL/CBL-B in non-myeloid malignancies and help test the potential for CBL/CBL-B inactivation in immunotherapy of tumors. PMID:27276677

  9. On operator strategic behavior

    NASA Technical Reports Server (NTRS)

    Hancock, P. A.

    1991-01-01

    Deeper and more detailed knowledge as to how human operators such as pilots respond, singly and in groups, to demands on their performance which arise from technical systems will support the manipulation of such systems' design in order to accommodate the foibles of human behavior. Efforts to understand how self-autonomy impacts strategic behavior and such related issues as error generation/recognition/correction are still in their infancy. The present treatment offers both general and aviation-specific definitions of strategic behavior as precursors of prospective investigations.

  10. 29 CFR 780.616 - Operations included in raising livestock.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Operations included in raising livestock. 780.616 Section... Employment in Agriculture and Livestock Auction Operations Under the Section 13(b)(13) Exemption Requirements for Exemption § 780.616 Operations included in raising livestock. Raising livestock includes such...

  11. 29 CFR 780.126 - Contract arrangements for raising poultry.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Contract arrangements for raising poultry. 780.126 Section... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.126 Contract arrangements for raising poultry. Feed dealers and processors sometimes enter into contractual...

  12. Strategic Help in User Interfaces for Information Retrieval.

    ERIC Educational Resources Information Center

    Brajnik, Giorgio; Mizzaro, Stefano; Tasso, Carlo; Venuti, Fabio

    2002-01-01

    Discussion of search strategy in information retrieval by end users focuses on the role played by strategic reasoning and design principles for user interfaces. Highlights include strategic help based on collaborative coaching; a conceptual model for strategic help; and a prototype knowledge-based system named FIRE. (Author/LRW)

  13. Robin Newmark - Executive Director for Strategic Initiatives | NREL

    Science.gov Websites

    Robin Newmark - Executive Director for Strategic Initiatives Robin Newmark - Executive Director for Strategic Initiatives A photo of Robin Newmark. At NREL, Robin Newmark focuses on the development of size and diversified its support. She previously served as the Director of the Strategic Energy

  14. Managing Uncertainty: Thinking and Planning Strategically.

    ERIC Educational Resources Information Center

    Lorenzo, Albert L.

    1993-01-01

    Argues that rapid change and tight resources demand reality-based planning, rather than planning models that ignore internal and external customers or emphasize process over product. Describes the Strategic Guidance Model (SGM) which provides colleges with strategic visioning, organizational assessment, environmental scanning, quality improvement,…

  15. Distance Education Strategy: Mental Models and Strategic Choices

    ERIC Educational Resources Information Center

    Adams, John C.; Seagren, Alan T.

    2004-01-01

    What issues do distance education (DE) leaders believe will influence the future of DE? What are their colleges' DE strategies? This qualitative study compares DE strategic thinking and strategic choices at three community colleges. Two propositions are investigated: (1) each college's DE leaders use common strategic mental models (ways of…

  16. The determinants of strategic thinking in preschool children.

    PubMed

    Brocas, Isabelle; Carrillo, Juan D

    2018-01-01

    Strategic thinking is an essential component of rational decision-making. However, little is known about its developmental aspects. Here we show that preschoolers can reason strategically in simple individual decisions that require anticipating a limited number of future decisions. This ability is transferred only partially to solve more complex individual decision problems and to efficiently interact with others. This ability is also more developed among older children in the classroom. Results indicate that while preschoolers potentially have the capacity to think strategically, it does not always translate into the ability to behave strategically.

  17. The determinants of strategic thinking in preschool children

    PubMed Central

    Brocas, Isabelle

    2018-01-01

    Strategic thinking is an essential component of rational decision-making. However, little is known about its developmental aspects. Here we show that preschoolers can reason strategically in simple individual decisions that require anticipating a limited number of future decisions. This ability is transferred only partially to solve more complex individual decision problems and to efficiently interact with others. This ability is also more developed among older children in the classroom. Results indicate that while preschoolers potentially have the capacity to think strategically, it does not always translate into the ability to behave strategically. PMID:29851954

  18. Strategic avionics technology planning

    NASA Technical Reports Server (NTRS)

    Cox, Kenneth J.; Brown, Don C.

    1991-01-01

    NASA experience in development and insertion of technology into programs had led to a recognition that a Strategic Plan for Avionics is needed for space. In the fall of 1989 an Avionics Technology Symposium was held in Williamsburg, Virginia. In early 1990, as a followon, a NASA wide Strategic Avionics Technology Working Group was chartered by NASA Headquarters. This paper will describe the objectives of this working group, technology bridging, and approaches to incentivize both the federal and commercial sectors to move toward rapidly developed, simple, and reliable systems with low life cycle cost.

  19. Integrating Risk Management and Strategic Planning

    ERIC Educational Resources Information Center

    Achampong, Francis K.

    2010-01-01

    Strategic planning is critical to ensuring that institutions of higher education thoughtfully and systematically position themselves to accomplish their mission, vision, and strategic goals, particularly when these institutions face a myriad of risks that can negatively impact their continued financial viability and compromise their ability to…

  20. Developing a Model for Strategic Leadership in Schools

    ERIC Educational Resources Information Center

    Davies, Barbara J.; Davies, Brent

    2006-01-01

    Strategic leadership is a critical component in the effective development of schools. Currently the educational debate is shifting to focus on how short-term improvements can become strategically sustainable. This article will put forward the view that renewed attention needs to be paid to the strategic dimension of leadership to ensure this…

  1. Peace and war: a study of morality and US strategic nuclear policies. Study project report

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

    Ginder, D.B.; Hicks, I.

    1983-05-01

    The paper examines the quesitons of peace and war and the morality of nuclear deterrence. These vital and enduring questions have been again become a focus of societal debate, especially in the light of the Catholic Bishop's pastoral letter. The nuclear debate is all encompassing, raising philosophical, political, social, strategic an religious questions. These issues present problems that each informed citizen will have to discern both morally and politically. The purpose of the paper is not to evaluate the morality of the defense and deterrent policies/strategies of the United States, but to provide the reader with the information to allowmore » him to formulate judgment on this important question and be able to reconcile personal moral values with national policy and strategy.« less

  2. The College President's Role in Fund Raising.

    ERIC Educational Resources Information Center

    Miller, Michael T.

    The role of the college president as one of the chief actors in academic fund raising is examined against the background of today's period of financial caution and increased competition for philanthropic support. The paper first provides an overview of the state of the art of fund raising and some ways in which college and universities have…

  3. Creating a nursing strategic planning framework based on evidence.

    PubMed

    Shoemaker, Lorie K; Fischer, Brenda

    2011-03-01

    This article describes an evidence-informed strategic planning process and framework used by a Magnet-recognized public health system in California. This article includes (1) an overview of the organization and its strategic planning process, (2) the structure created within nursing for collaborative strategic planning and decision making, (3) the strategic planning framework developed based on the organization's balanced scorecard domains and the new Magnet model, and (4) the process undertaken to develop the nursing strategic priorities. Outcomes associated with the structure, process, and key initiatives are discussed throughout the article. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Transforming Student Affairs Strategic Planning into Tangible Results

    ERIC Educational Resources Information Center

    Taylor, Simone Himbeault; Matney, Malinda M.

    2007-01-01

    The Division of Student Affairs at the University of Michigan has engaged in an iterative strategic process to create and implement a set of long-range goals. This strategic journey continues to evolve, bringing together the guiding framework of strategic planning steps, a reflective process with an assessment component within each step, and a…

  5. Collaborative Strategic Planning in Higher Education

    ERIC Educational Resources Information Center

    Sanaghan, Patrick

    2009-01-01

    This book outlines a simple, five-phase collaborative approach to strategic planning that has worked effectively on many campuses. Specifically, Collaborative Strategic Planning (CSP) refers to the disciplined and thoughtful process of meaningfully engaging relevant stakeholders in creating a shared future vision and goals for their institution.…

  6. 24 CFR 91.315 - Strategic plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Strategic plan. 91.315 Section 91... CONSOLIDATED SUBMISSIONS FOR COMMUNITY PLANNING AND DEVELOPMENT PROGRAMS State Governments; Contents of Consolidated Plan § 91.315 Strategic plan. (a) General. For the categories described in paragraphs (b), (c), (d...

  7. Achieving competitive advantage through strategic human resource management.

    PubMed

    Fottler, M D; Phillips, R L; Blair, J D; Duran, C A

    1990-01-01

    The framework presented here challenges health care executives to manage human resources strategically as an integral part of the strategic planning process. Health care executives should consciously formulate human resource strategies and practices that are linked to and reinforce the broader strategic posture of the organization. This article provides a framework for (1) determining and focusing on desired strategic outcomes, (2) identifying and implementing essential human resource management actions, and (3) maintaining or enhancing competitive advantage. The strategic approach to human resource management includes assessing the organization's environment and mission; formulating the organization's business strategy; assessing the human resources requirements based on the intended strategy; comparing the current inventory of human resources in terms of numbers, characteristics, and human resource management practices with respect to the strategic requirements of the organization and its services or product lines; formulating the human resource strategy based on the differences between the assessed requirements and the current inventory; and implementing the appropriate human resource practices to reinforce the strategy and attain competitive advantage.

  8. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

    DOE PAGES

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; ...

    2015-06-08

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

  9. Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

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

    Wang, Yang; Xu, Zhidong; Mao, Jian -Hua

    Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

  10. An exploratory study of healthcare strategic planning in two metropolitan areas.

    PubMed

    Begun, James W; Kaissi, Amer A

    2005-01-01

    Little is known about empirical variation in the extent to which healthcare organizations conduct formal strategic planning or the extent to which strategic planning affects performance. Structural contingency and complexity science theory offer differing interpretations of the value of strategic planning. Structural contingency theory emphasizes adaptation to achieve organizational fit with a changing environment and views strategic planning as a way to chart the organization's path. Complexity science argues that planning is largely futile in changing environments. Interviews of leaders in 20 healthcare organizations in the metropolitan areas of Minneapolis/St. Paul, Minnesota, and San Antonio, Texas, reveal that strategic planning is a common and valued function in healthcare organizations. Respondents emphasized the need to continuously update strategic plans, involve physicians and the governing board, and integrate strategic plans with other organizational plans. Most leaders expressed that strategic planning contributes to organizational focus, fosters stakeholder participation and commitment, and leads to achievement of strategic goals. Because the widespread belief in strategic planning is based largely on experience, intuition, and faith, we present recommendations for developing an evidence base for healthcare strategic planning.

  11. Strategic Sealift Supporting Army Deployments

    DTIC Science & Technology

    2016-06-10

    Approved for Public Release; Distribution is Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Mobility is a key element of the US Army’s ability to...together. There are three means the Army relies on for strategic mobility : airlift, sealift, and pre-positioning. Each of these modes has advantages...important than ever. Strategic mobility by either airlift or sealift is among the largest of the force’s routine expenditures and as such demands

  12. Strategic Sourcing in the Army

    DTIC Science & Technology

    2013-09-01

    200 words) The objective of this project is to examine how the Army is utilizing strategic sourcing as an effective process for getting the best...redundancy in the acquisition process. The discussions will also look at how important internal customer requirements and external marketplace ...to examine how the Army is utilizing strategic sourcing as an effective process for getting the best overall value for acquiring goods and services

  13. 29 CFR 780.125 - Raising of poultry in general.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Raising of poultry in general. 780.125 Section 780.125... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.125 Raising of poultry in general. (a) The term “poultry” includes domesticated fowl and game birds. Ducks and...

  14. Strategic Planning towards a World-Class University

    NASA Astrophysics Data System (ADS)

    Usoh, E. J.; Ratu, D.; Manongko, A.; Taroreh, J.; Preston, G.

    2018-02-01

    Strategic planning with a focus on world-class university status is an option that cannot be avoided by universities today to survive and succeed in competition as a provider of higher education. The objective of this research is to obtain exploratory research results on the strategic plans of universities that are prepared to generate world-class university status. This research utilised exploratory qualitative research method and data was collected by in-depth interviews method. Interview transcripts were analyzed by using thematic content analysis through NVivo software analysis and manual systems. The main finding of interview shows that most interviewees agreed that UNIMA has been engaged in strategic planning. Contribution from faculties and schools are acknowledged and inform the planning process. However, a new model of strategic planning should be adopted by UNIMA due to the shift towards a “corporate university”. The finding results from documents, literature review and interview were the addition of world-class university characteristics and features to current strategic planning of UNIMA and how to upgrade by considering to use the characteristics and features towards world-class university.

  15. The U.S. Geological Survey Strategic Plan 1999-2009

    USGS Publications Warehouse

    ,

    1999-01-01

    This new version of the USGS Strategic Plan builds on our first strategic plan, which was developed in 1996, and focuses specifically on strategic goals in four areas: customers, programs, people, and operations of the USGS.

  16. Strategic group stability: evidence from the health care industry.

    PubMed

    Churchman, Richard L; Woodard, Beth

    2004-01-01

    To better understand strategic group stability and the associated mobility barriers concept, we surveyed health care administrators on their reasons for remaining in their current strategic group. We offer administrators' responses to the strategic group stability (mobility barrier) question. Decision-makers may be unaware of these cognitive biases (e.g., group-level world-view and resource similarity) and may not recognize the extent to which they are reducing their strategic alternatives.

  17. A strategic informatics approach to autoverification.

    PubMed

    Jones, Jay B

    2013-03-01

    Autoverification is rapidly expanding with increased functionality provided by middleware tools. It is imperative that autoverification of laboratory test results be viewed as a process evolving into a broader, more sophisticated form of decision support, which will require strategic planning to form a foundational tool set for the laboratory. One must strategically plan to expand autoverification in the future to include a vision of instrument-generated order interfaces, reflexive testing, and interoperability with other information systems. It is hoped that the observations, examples, and opinions expressed in this article will stimulate such short-term and long-term strategic planning. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Strategic orientations of small multihospital systems.

    PubMed Central

    Luke, R D; Begun, J W

    1988-01-01

    Strategic behaviors of organizations can be classified along two dimensions--growth orientations, or patterns of evolution over time, and action orientations, or strategic aggressiveness in undertaking a particular growth orientation. We create measures of growth and action orientations for small multihospital systems and test the validity of the growth and action orientation typologies, using data from a sample of small multihospital systems. Growth and action orientations do appear to exist independently of each other, and they are related to the ownership status of the systems. Not-for-profit and church-other systems exhibit similar strategic orientations, unlike those of Catholic and investor-owned systems. PMID:3060448

  19. Evolution in strategic forces and doctrine

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

    Canavan, G.H.

    The era of the deterrence through the threat of retaliation is ending. Strategic defense opens new options for deep reductions without loss of stability, which could be a guide for shifting from the residual forces from the offensive era into those appropriate for a multipolar world. There are strong arguments for retiring missiles under the cover of missile defenses and returning to fewer but more capable aircraft for strategic roles. Developing the technologies for theater and strategic defenses could largely eliminate the incentive for the development of missiles by the third world and shift their efforts into more stabilizing areas.more » 20 refs.« less

  20. 75 FR 47346 - Draft Strategic Plan for FY 2010-2015

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ...://www.treas.gov/offices/management/budget/strategic-plan/2007-2012/strategic-plan2007-2012.pdf . The....ustreas.gov/offices/management/budget/strategic-plan/ and by clicking on the comment link. Comments may... DEPARTMENT OF THE TREASURY Draft Strategic Plan for FY 2010-2015 AGENCY: United States Department...

  1. 29 CFR 780.124 - Raising of fur-bearing animals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Raising of fur-bearing animals. 780.124 Section 780.124... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.124 Raising of fur-bearing animals. (a) The term “fur-bearing animals” has reference to animals which bear fur of...

  2. 29 CFR 780.124 - Raising of fur-bearing animals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Raising of fur-bearing animals. 780.124 Section 780.124... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.124 Raising of fur-bearing animals. (a) The term “fur-bearing animals” has reference to animals which bear fur of...

  3. 29 CFR 780.124 - Raising of fur-bearing animals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Raising of fur-bearing animals. 780.124 Section 780.124... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.124 Raising of fur-bearing animals. (a) The term “fur-bearing animals” has reference to animals which bear fur of...

  4. 29 CFR 780.124 - Raising of fur-bearing animals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Raising of fur-bearing animals. 780.124 Section 780.124... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.124 Raising of fur-bearing animals. (a) The term “fur-bearing animals” has reference to animals which bear fur of...

  5. 29 CFR 780.124 - Raising of fur-bearing animals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Raising of fur-bearing animals. 780.124 Section 780.124... General Scope of Agriculture Raising of Livestock, Bees, Fur-Bearing Animals, Or Poultry § 780.124 Raising of fur-bearing animals. (a) The term “fur-bearing animals” has reference to animals which bear fur of...

  6. Advancing the state of the art in healthcare strategic planning.

    PubMed

    Zuckerman, Alan M

    2006-01-01

    A recent survey of the state of strategic planning among healthcare organizations indicates that planners and executives believe that healthcare strategic planning practices are effective and provide the appropriate focus and direction for their organizations. When compared to strategic planning practices employed outside of the healthcare field, however, most healthcare strategic planning processes have not evolved to the more advanced, state-of-the-art levels of planning being used successfully outside of healthcare. While organizations that operate in stable markets may be able to survive using basic strategic planning practices, the volatile healthcare market demands that providers be nimble competitors with advanced, ongoing planning processes that drive growth and organizational effectiveness. What should healthcare organizations do to increase the rigor and sophistication of their strategic planning practices? This article identifies ten current healthcare strategic planning best practices and recommends five additional innovative approaches from pathbreaking companies outside of healthcare that have used advanced strategic planning practices to attain high levels of organizational success.

  7. Using Appropriate Tools Strategically for Instruction

    ERIC Educational Resources Information Center

    Sherman, Milan; Cayton, Charity

    2015-01-01

    Students' ability to use appropriate tools strategically is an important skill of mathematically proficient students (SMP 5, CCSSI 2010, p. 7). A parallel practice for teachers is using appropriate tools strategically for mathematics instruction. An important element of this practice is that the use of technology depends on the goals of…

  8. Introduction of International Microgravity Strategic Planning Group

    NASA Technical Reports Server (NTRS)

    Rhome, Robert

    1998-01-01

    Established in May 6, 1995, the purpose of this International Strategic Planning Group for Microgravity Science and Applications Research is to develop and update, at least on a biennial basis, an International Strategic Plan for Microgravity Science and Applications Research. The member space agencies have agreed to contribute to the development of a Strategic Plan, and seek the implementation of the cooperative programs defined in this Plan. The emphasis of this plan is the coordination of hardware construction and utilization within the various areas of research including biotechnology, combustion science, fluid physics, materials science and other special topics in physical sciences. The Microgravity Science and Applications International Strategic Plan is a joint effort by the present members - ASI, CNES, CSA, DLR, ESA, NASA, and NASDA. It represents the consensus from a series of discussions held within the International Microgravity Strategic Planning Group (IMSPG). In 1996 several space agencies initiated multilateral discussions on how to improve the effectiveness of international microgravity research during the upcoming Space Station era. These discussions led to a recognition of the need for a comprehensive strategic plan for international microgravity research that would provide a framework for cooperation between international agencies. The Strategic Plan is intended to provide a basis for inter-agency coordination and cooperation in microgravity research in the environment of the International Space Station (ISS) era. This will be accomplished through analysis of the interests and goals of each participating agency and identification of mutual interests and program compatibilities. The Plan provides a framework for maximizing the productivity of space-based research for the benefit of our societies.

  9. Implementing successful strategic plans: a simple formula.

    PubMed

    Blondeau, Whitney; Blondeau, Benoit

    2015-01-01

    Strategic planning is a process. One way to think of strategic planning is to envision its development and design as a framework that will help your hospital navigate through internal and external changing environments over time. Although the process of strategic planning can feel daunting, following a simple formula involving five steps using the mnemonic B.E.G.I.N. (Begin, Evaluate, Goals & Objectives, Integration, and Next steps) will help the planning process feel more manageable, and lead you to greater success.

  10. Measuring strategic control in implicit learning: how and why?

    PubMed

    Norman, Elisabeth

    2015-01-01

    Several methods have been developed for measuring the extent to which implicitly learned knowledge can be applied in a strategic, flexible manner. Examples include generation exclusion tasks in Serial Reaction Time (SRT) learning (Goschke, 1998; Destrebecqz and Cleeremans, 2001) and 2-grammar classification tasks in Artificial Grammar Learning (AGL; Dienes et al., 1995; Norman et al., 2011). Strategic control has traditionally been used as a criterion for determining whether acquired knowledge is conscious or unconscious, or which properties of knowledge are consciously available. In this paper I first summarize existing methods that have been developed for measuring strategic control in the SRT and AGL tasks. I then address some methodological and theoretical questions. Methodological questions concern choice of task, whether the measurement reflects inhibitory control or task switching, and whether or not strategic control should be measured on a trial-by-trial basis. Theoretical questions concern the rationale for including measurement of strategic control, what form of knowledge is strategically controlled, and how strategic control can be combined with subjective awareness measures.

  11. Measuring strategic control in implicit learning: how and why?

    PubMed Central

    Norman, Elisabeth

    2015-01-01

    Several methods have been developed for measuring the extent to which implicitly learned knowledge can be applied in a strategic, flexible manner. Examples include generation exclusion tasks in Serial Reaction Time (SRT) learning (Goschke, 1998; Destrebecqz and Cleeremans, 2001) and 2-grammar classification tasks in Artificial Grammar Learning (AGL; Dienes et al., 1995; Norman et al., 2011). Strategic control has traditionally been used as a criterion for determining whether acquired knowledge is conscious or unconscious, or which properties of knowledge are consciously available. In this paper I first summarize existing methods that have been developed for measuring strategic control in the SRT and AGL tasks. I then address some methodological and theoretical questions. Methodological questions concern choice of task, whether the measurement reflects inhibitory control or task switching, and whether or not strategic control should be measured on a trial-by-trial basis. Theoretical questions concern the rationale for including measurement of strategic control, what form of knowledge is strategically controlled, and how strategic control can be combined with subjective awareness measures. PMID:26441809

  12. Capital raising of aerospace companies: equities or debts?

    NASA Astrophysics Data System (ADS)

    Hui-Shan, L.; Taw-Onn, Y.; Wai-Mun, H.

    2016-10-01

    Aerospace products enhance national and economic activities, thus maintaining the sustainability of aerospace industry is crucial. One of the perspectives in ensuring sustainability of aerospace companies is expansion of firms by raising funds for research and development in order to provide a reasonable profitability to the firms. This study comprises a sample of 47 aerospace companies from 2009 to 2015 to analyze the impact of raising fund by equities or debts to the profitability of the firms. The result indicates that capital raising through equities is preferable than debts. Moreover, the study also identifies that the profit of aerospace industry is volatile and there is cyclical reduction of the net income in the first quarter of the year. The management needs to make wise decisions in raising fund to ensure a healthy growth of the aerospace company.

  13. [Design and application of medical electric leg-raising machine].

    PubMed

    Liang, Jintang; Chen, Jinyuan; Zhao, Zixian; Lin, Jinfeng; Li, Juanhong; Zhong, Jingliang

    2017-08-01

    Passive leg raising is widely used in clinic, but it lacks of specialized mechanical raise equipment. It requires medical staff to raise leg by hand or requires a multi-functional bed to raise leg, which takes time and effort. Therefore we have developed a new medical electric leg-raising machine. The equipment has the following characteristics: simple structure, stable performance, easy operation, fast and effective, safe and comfortable. The height range of the lifter is 50-120 cm, the range of the angle of raising leg is 10degree angle-80degree angle, the maximum supporting weight is 40 kg. Because of raising the height of the lower limbs and making precise angle, this equipment can completely replace the traditional manner of lifting leg by hand with multi-functional bed to lift patients' leg and can reduce the physical exhaustion and time consumption of medical staff. It can change the settings at any time to meet the needs of the patient; can be applied to the testing of PLR and dynamically assessing the hemodynamics; can prevent deep vein thrombosis and some related complications of staying in bed; and the machine is easy to be cleaned and disinfected, which can effectively avoid hospital acquired infection and cross infection; and can also be applied to emergency rescue of various disasters and emergencies.

  14. The Strategic Data Project's Strategic Performance Indicators

    ERIC Educational Resources Information Center

    Page, Lindsay C.; Fullerton, Jon; Bacher-Hicks, Andrew; Owens, Antoniya; Cohodes, Sarah R.; West, Martin R.; Glover, Sarah

    2013-01-01

    Strategic Performance Indicators (SPIs) are summary measures derived from parallel, descriptive analyses conducted across educational agencies. The SPIs are designed to inform agency management and efforts to improve student outcomes. We developed the SPIs to reveal patterns common across partner agencies, to highlight exceptions to those…

  15. Aligning business and information technology domains: strategic planning in hospitals.

    PubMed

    Henderson, J C; Thomas, J B

    1992-01-01

    This article develops a framework for strategic information technology (IT) management in hospitals, termed the Strategic Alignment Model. This model is defined in terms of four domains--business strategy, IT strategy, organizational infrastructure, and IT infrastructure--each with its constituent components. The concept of strategic alignment is developed using two fundamental dimensions--strategic fit and integration. Different perspectives that hospitals use for aligning the various domains are discussed, and a prescriptive model of strategic IT planning is proposed.

  16. Modernization and unification: Strategic goals for NASA STI program

    NASA Technical Reports Server (NTRS)

    Blados, W.; Cotter, Gladys A.

    1993-01-01

    Information is increasingly becoming a strategic resource in all societies and economies. The NASA Scientific and Technical Information (STI) Program has initiated a modernization program to address the strategic importance and changing characteristics of information. This modernization effort applies new technology to current processes to provide near-term benefits to the user. At the same time, we are developing a long-term modernization strategy designed to transition the program to a multimedia, global 'library without walls.' Notwithstanding this modernization program, it is recognized that no one information center can hope to collect all the relevant data. We see information and information systems changing and becoming more international in scope. We are finding that many nations are expending resources on national systems which duplicate each other. At the same time that this duplication exists, many useful sources of aerospace information are not being collected because of resource limitations. If nations cooperate to develop an international aerospace information system, resources can be used efficiently to cover expanded sources of information. We must consider forming a coalition to collect and provide access to disparate, multidisciplinary sources of information, and to develop standardized tools for documenting and manipulating this data and information. In view of recent technological developments in information science and technology, as well as the reality of scarce resources in all nations, it is time to explore the mutually beneficial possibilities offered by cooperation and international resource sharing. International resources need to be mobilized in a coordinated manner to move us towards this goal. This paper reviews the NASA modernization program and raises for consideration new possibilities for unification of the various aerospace database efforts toward a cooperative international aerospace database initiative that can optimize the cost

  17. [Strategic planning and mental health policies].

    PubMed

    Tonini, Nelsi Salete; Kantorski, Luciane Prado

    2007-03-01

    This article discusses how mental health policies are prioritized in the process of strategic planning of mental health actions within the context of Brazilian psychiatric reform. The theoretical support of strategic planning provide health professionals, particularly those involved in metal health, with elements fir deepening discussions on existing mental health actions and policies.

  18. Cypress College Strategic Plan, 2000-2004.

    ERIC Educational Resources Information Center

    Cypress Coll., CA.

    This document outlines Cypress College's Strategic Plan to be used to guide decision-making and resource allocation for the years 2000 through 2004. The Strategic Plan begins with the Cypress College Vision Statement: building a college-wide learning community for student success. The Mission Statement states that Cypress College is committed to…

  19. 24 CFR 91.415 - Strategic plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Strategic plan. 91.415 Section 91... Plan § 91.415 Strategic plan. Strategies and priority needs must be described in the consolidated plan... addressing underserved needs. (Approved by the Office of Management and Budget under control number 2506-0117) ...

  20. 24 CFR 91.415 - Strategic plan.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Strategic plan. 91.415 Section 91... Plan § 91.415 Strategic plan. Strategies and priority needs must be described in the consolidated plan... addressing underserved needs. (Approved by the Office of Management and Budget under control number 2506-0117) ...

  1. Executive plan summary, an ITS strategic plan for Texas.

    DOT National Transportation Integrated Search

    2016-07-01

    The TxDOT ITS Strategic Plan supports the goals and objectives of the TxDOT agency Strategic : Plan. It has the same four goals as the TxDOT Strategic Plan: : - Maintain a safe system. : - Address congestion. : - Connect Texas communities. : - Become...

  2. Strategic Planning and Strategic Thinking Clothed in STRATEGO

    ERIC Educational Resources Information Center

    Baaki, John; Moseley, James L.

    2011-01-01

    This article shares experiences that participants had playing the game of STRATEGO and how the activity may be linked to strategic planning and thinking. Among the human performance technology implications of playing this game are that gamers agreed on a framework for rules, took stock on where they wanted to go in the future, and generated a risk…

  3. Factors affecting strategic plan implementation using interpretive structural modeling (ISM).

    PubMed

    Bahadori, Mohammadkarim; Teymourzadeh, Ehsan; Tajik, Hamidreza; Ravangard, Ramin; Raadabadi, Mehdi; Hosseini, Seyed Mojtaba

    2018-06-11

    Purpose Strategic planning is the best tool for managers seeking an informed presence and participation in the market without surrendering to changes. Strategic planning enables managers to achieve their organizational goals and objectives. Hospital goals, such as improving service quality and increasing patient satisfaction cannot be achieved if agreed strategies are not implemented. The purpose of this paper is to investigate the factors affecting strategic plan implementation in one teaching hospital using interpretive structural modeling (ISM). Design/methodology/approach The authors used a descriptive study involving experts and senior managers; 16 were selected as the study sample using a purposive sampling method. Data were collected using a questionnaire designed and prepared based on previous studies. Data were analyzed using ISM. Findings Five main factors affected strategic plan implementation. Although all five variables and factors are top level, "senior manager awareness and participation in the strategic planning process" and "creating and maintaining team participation in the strategic planning process" had maximum drive power. "Organizational structure effects on the strategic planning process" and "Organizational culture effects on the strategic planning process" had maximum dependence power. Practical implications Identifying factors affecting strategic plan implementation is a basis for healthcare quality improvement by analyzing the relationship among factors and overcoming the barriers. Originality/value The authors used ISM to analyze the relationship between factors affecting strategic plan implementation.

  4. Departure Queue Prediction for Strategic and Tactical Surface Scheduler Integration

    NASA Technical Reports Server (NTRS)

    Zelinski, Shannon; Windhorst, Robert

    2016-01-01

    A departure metering concept to be demonstrated at Charlotte Douglas International Airport (CLT) will integrate strategic and tactical surface scheduling components to enable the respective collaborative decision making and improved efficiency benefits these two methods of scheduling provide. This study analyzes the effect of tactical scheduling on strategic scheduler predictability. Strategic queue predictions and target gate pushback times to achieve a desired queue length are compared between fast time simulations of CLT surface operations with and without tactical scheduling. The use of variable departure rates as a strategic scheduler input was shown to substantially improve queue predictions over static departure rates. With target queue length calibration, the strategic scheduler can be tuned to produce average delays within one minute of the tactical scheduler. However, root mean square differences between strategic and tactical delays were between 12 and 15 minutes due to the different methods the strategic and tactical schedulers use to predict takeoff times and generate gate pushback clearances. This demonstrates how difficult it is for the strategic scheduler to predict tactical scheduler assigned gate delays on an individual flight basis as the tactical scheduler adjusts departure sequence to accommodate arrival interactions. Strategic/tactical scheduler compatibility may be improved by providing more arrival information to the strategic scheduler and stabilizing tactical scheduler changes to runway sequence in response to arrivals.

  5. Tamoxifen dosing for Cre-mediated recombination in experimental bronchopulmonary dysplasia.

    PubMed

    Ruiz-Camp, Jordi; Rodríguez-Castillo, José Alberto; Herold, Susanne; Mayer, Konstantin; Vadász, István; Tallquist, Michelle D; Seeger, Werner; Ahlbrecht, Katrin; Morty, Rory E

    2017-02-01

    Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth characterized by blunted post-natal lung development. BPD can be modelled in mice by exposure of newborn mouse pups to elevated oxygen levels. Little is known about the mechanisms of perturbed lung development associated with BPD. The advent of transgenic mice, where genetic rearrangements can be induced in particular cell-types at particular time-points during organogenesis, have great potential to explore the pathogenic mechanisms at play during arrested lung development. Many inducible, conditional transgenic technologies available rely on the application of the estrogen-receptor modulator, tamoxifen. While tamoxifen is well-tolerated and has been widely employed in adult mice, or in healthy developing mice; tamoxifen is not well-tolerated in combination with hyperoxia, in the most widely-used mouse model of BPD. To address this, we set out to establish a safe and effective tamoxifen dosing regimen that can be used in newborn mouse pups subjected to injurious stimuli, such as exposure to elevated levels of environmental oxygen. Our data reveal that a single intraperitoneal dose of tamoxifen of 0.2 mg applied to newborn mouse pups in 10 μl Miglyol vehicle was adequate to successfully drive Cre recombinase-mediated genome rearrangements by the fifth day of life, in a murine model of BPD. The number of recombined cells was comparable to that observed in regular tamoxifen administration protocols. These findings will be useful to investigators where tamoxifen dosing is problematic in the background of injurious stimuli and mouse models of human and veterinary disease.

  6. Purdue Extended Campus: Transparency, Accountability, and Assessment in Strategic Planning

    ERIC Educational Resources Information Center

    Cunningham, Robin; Eddy, Michael; Pagano, Mark; Ncube, Lisa

    2011-01-01

    In 2002 President Martin Jischke initiated a new era in strategic planning at Purdue. Under his leadership, strategic planning became a centralized activity with unit plans aligned to the university plan. Strategic goals were designed to have maximum impact, which would be measurable through metrics. Strategic planning at Purdue would be an…

  7. U.S. Department of Transportation strategic plan

    DOT National Transportation Integrated Search

    2010-01-01

    This Strategic Plan describes the Department of Transportations new ideas through : goals, strategies and the results we will achieve to improve the United States : transportation sector. We have set policy goals in five strategic areas: Safety, R...

  8. Strategic planning for pain practice growth.

    PubMed

    Van Horn, L M

    2000-01-01

    Strategy formation involves understanding the environment and strengths and weaknesses of a practice to develop a game plan to achieve goals. It starts with the creation of a mission statement that defines a long-term vision of what the practice seeks to be and the markets it seeks to serve. Once the mission of the practice is understood, the target markets and competition must be analyzed prior to defining the goals. Once a strategic plan is developed, communication with all employees is crucial. Everything that the practice does should be in support of the strategic plan and in pursuit of obtaining the goals contained within. Once created, the strategic plan is the foundation of the practice and should only be changed for compelling reasons such as a competitive threat, environmental changes, or trends in purchasing behavior. Reviewing the strategic plan once a year, making periodic reappraisals and fine-tuning adjustments as the environment changes is crucial. This helps ensure that the practice avoids complacency and affirms that it is in the right business and achieving the desired results.

  9. Definitions of Tactical and Strategic: An Informal Study

    NASA Technical Reports Server (NTRS)

    Schutte, Paul C.

    2004-01-01

    Seventeen subject matter experts defined tactical and strategic within the aviation domain. They provided five verbs and a sentence describing both behaviors. The verbs for strategic behavior were Plan, Think, Arrange, Formulate, Intend, Devise, Anticipate, and Order. The verbs for tactical behavior were Act, Fly, Respond, Do, Avoid, Control, React, and Move. Verbs that were common to both were Get Information, Navigate, Know, Execute, Manage, Perceive, Understand, Direct, Concentrate, and Point. The responses highlight the difference between planning (strategic) and carrying out those plans (tactical). Tactical verbs are more action-oriented that change the state of the world after they have been accomplished. Strategic verbs are more prescriptive in that they do not change the state of the world but offer a procedure or program for changing the world. The pilot is in a tactical mode when actually moving the aircraft and in a strategic mode when thinking about moving it.

  10. CNES Strategic Plan 2001-2005

    NASA Astrophysics Data System (ADS)

    Janichewski, S.; Ben Aı̈m, H.

    2004-04-01

    CNES's latest strategic plan defines the French space agency's strategic focus and charts its course for the 2001-2005 timeframe. Based on a vision of how the space sector will evolve over the period up to 2010, the Strategic Plan sets out the agency's ambition for 2005: " CNES—space technology serving society". This ambition is structured around four challenges: Focusing actions on society's needs in three areas where space technology can make a major difference—environment, science and the information society and mobility. Building the foundation for success by ensuring competitive access to space and boosting basic research and technological innovation. Strengthening national and European synergies to ensure complementarity between: the ESA European framework, which is well adapted for major projects and the development of a European Space Strategy (ESS); and the national framework to support activities of national responsibility such as defence, science and technology development, and to improve competitiveness through direct international cooperation with other space agencies. Forging effective partnerships with its research and industry partners in Europe and France to enhance performance by: developing a service culture; building partnerships; concentrating on core competencies where it can most add value; improving skills and responsiveness in line with its strategic position; ensuring transparent and rigorous management of public funds. This Strategic Plan will be implemented in the 2001-2005 timeframe at all management levels. Implementation will be eased by the fact that the plan has been drawn up through a specific process designed to make internal management aware of the analysis underlying it. This will ensure that all stakeholders understand and appropriate the plan's orientations and thus play an active role in CNES' development. This process involved five successive steps: shared assessment of the space sector's evolution, providing a common

  11. NATO Cyberspace Capability: A Strategic and Operational Evolution

    DTIC Science & Technology

    2016-06-01

    Coalition 2012 was run concur- 24 rently with the annual NATO Crisis Management Ex - ercise (CMX), an internal command post exercise that does not involve...concerning the role of ground forces in achieving national security objectives. The Strategic Studies Institute publishes national security and...international audience, and honor Soldiers—past and present. STRATEGIC STUDIES INSTITUTE The Strategic Studies Institute (SSI) is part of the U.S

  12. Department of Defense Civilian Human Resources Strategic Plan

    DTIC Science & Technology

    2005-04-01

    the strategic plan. A balanced scorecard approach was used to build the strategic plan. The balanced scorecard is a strategic management tool that...in the balanced scorecard format. Details of how the balanced scorecard addresses the DoD Human Capital Initiative are outlined in the Office of...mission- ready civilian workforce 8 GOALS AND OBJECTIVES The balanced scorecard approach reflects the changes the Department is undergoing and

  13. Cell-type specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing

    PubMed Central

    Sun, Yanjun; Nguyen, Amanda; Nguyen, Joseph; Le, Luc; Saur, Dieter; Choi, Jiwon; Callaway, Edward M.; Xu, Xiangmin

    2014-01-01

    Summary We applied a new Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to CA1 excitatory and inhibitory neuron types in mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, entorhinal cortex and the medial septum (MS), and unexpectedly also from the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons while inhibitory CA1 neurons receive a great majority of input from GABAergic MS neurons; both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons receive much stronger input than SOM+ neurons from CA3, entorhinal cortex and MS. Differential input from CA3 to specific CA1 cell types was also demonstrated functionally using laser scanning photostimulation and whole cell recordings. PMID:24656815

  14. Corporate strategic philanthropy: implications for social work.

    PubMed

    Marx, J D

    1998-01-01

    Corporate contributions to health and human services have declined from a high of 42.0 percent of total corporate giving in 1972 to 25.3 percent in 1994. At the same time, "strategic philanthropy" has become the state of the art in corporate contributions management. Strategic philanthropy is defined in this article as the process by which contributions are targeted to meet both business objectives and recipient needs. This concept represents the integration of philanthropy into the overall strategic planning of the corporation. This article describes a national survey of corporate philanthropy programs that examined the activities that characterize the strategic management of corporate philanthropy. Results suggest that corporations do not frequently evaluate their philanthropy programs. Social work professionals may use this information to increase their opportunities to provide evaluative input and to increase corporate funding of health and human services.

  15. Learning Spaces as a Strategic Priority

    ERIC Educational Resources Information Center

    George, Gene; Erwin, Tom; Barnes, Briony

    2009-01-01

    In April 2007 Butler Community College made learning spaces one of its five strategic priorities. The college had just completed a major renovation of the work spaces for the IT division and had started a project to build a student union and create informal learning spaces at the Andover campus. With learning spaces becoming a strategic priority,…

  16. Rocky Mountain Research Station: Strategic Framework

    Treesearch

    Lane Eskew

    2003-01-01

    A strategic plan is a tool for charting a path into the future. This Strategic Framework will help guide the USDA Forest Service Rocky Mountain Research Station over the next decade during inevitable socioeconomic and environmental change. It is the product of a dialog with our stakeholders and employees to examine the Station's capabilities, anticipate research...

  17. Strategic Human Resource Planning in Academia

    ERIC Educational Resources Information Center

    Ulferts, Gregory; Wirtz, Patrick; Peterson, Evan

    2009-01-01

    A strategic plan guides a college in successfully meeting its mission. Based on the strategic plan, a college can develop a human resource plan that will allow it to make management decisions in the present to support the future direction of the college. The overall purpose of human resource management is to: (1) ensure the organization has…

  18. Strategic planning in healthcare organizations.

    PubMed

    Rodríguez Perera, Francisco de Paula; Peiró, Manel

    2012-08-01

    Strategic planning is a completely valid and useful tool for guiding all types of organizations, including healthcare organizations. The organizational level at which the strategic planning process is relevant depends on the unit's size, its complexity, and the differentiation of the service provided. A cardiology department, a hemodynamic unit, or an electrophysiology unit can be an appropriate level, as long as their plans align with other plans at higher levels. The leader of each unit is the person responsible for promoting the planning process, a core and essential part of his or her role. The process of strategic planning is programmable, systematic, rational, and holistic and integrates the short, medium, and long term, allowing the healthcare organization to focus on relevant and lasting transformations for the future. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  19. Improving the Success of Strategic Management Using Big Data.

    PubMed

    Desai, Sapan S; Wilkerson, James; Roberts, Todd

    2016-01-01

    Strategic management involves determining organizational goals, implementing a strategic plan, and properly allocating resources. Poor access to pertinent and timely data misidentifies clinical goals, prevents effective resource allocation, and generates waste from inaccurate forecasting. Loss of operational efficiency diminishes the value stream, adversely impacts the quality of patient care, and hampers effective strategic management. We have pioneered an approach using big data to create competitive advantage by identifying trends in clinical practice, accurately anticipating future needs, and strategically allocating resources for maximum impact.

  20. Preliminary Strategic Environmental Assessment of the Great Western Development Strategy: Safeguarding Ecological Security for a New Western China

    NASA Astrophysics Data System (ADS)

    Li, Wei; Liu, Yan-Ju; Yang, Zhifeng

    2012-02-01

    The Great Western Development Strategy (GWDS) is a long term national campaign aimed at boosting development of the western area of China and narrowing the economic gap between the western and the eastern parts of China. The Strategic Environmental Assessment (SEA) procedure was employed to assess the environmental challenges brought about by the western development plans. These plans include five key developmental domains (KDDs): water resource exploitation and use, land utilization, energy generation, tourism development, and ecological restoration and conservation. A combination of methods involving matrix assessment, incorporation of expert judgment and trend analysis was employed to analyze and predict the environmental impacts upon eight selected environmental indicators: water resource availability, soil erosion, soil salinization, forest destruction, land desertification, biological diversity, water quality and air quality. Based on the overall results of the assessment, countermeasures for environmental challenges that emerged were raised as key recommendations to ensure ecological security during the implementation of the GWDS. This paper is intended to introduce a consensus-based process for evaluating the complex, long term pressures on the ecological security of large areas, such as western China, that focuses on the use of combined methods applied at the strategic level.

  1. Preliminary strategic environmental assessment of the Great Western Development Strategy: safeguarding ecological security for a new western China.

    PubMed

    Li, Wei; Liu, Yan-ju; Yang, Zhifeng

    2012-02-01

    The Great Western Development Strategy (GWDS) is a long term national campaign aimed at boosting development of the western area of China and narrowing the economic gap between the western and the eastern parts of China. The Strategic Environmental Assessment (SEA) procedure was employed to assess the environmental challenges brought about by the western development plans. These plans include five key developmental domains (KDDs): water resource exploitation and use, land utilization, energy generation, tourism development, and ecological restoration and conservation. A combination of methods involving matrix assessment, incorporation of expert judgment and trend analysis was employed to analyze and predict the environmental impacts upon eight selected environmental indicators: water resource availability, soil erosion, soil salinization, forest destruction, land desertification, biological diversity, water quality and air quality. Based on the overall results of the assessment, countermeasures for environmental challenges that emerged were raised as key recommendations to ensure ecological security during the implementation of the GWDS. This paper is intended to introduce a consensus-based process for evaluating the complex, long term pressures on the ecological security of large areas, such as western China, that focuses on the use of combined methods applied at the strategic level.

  2. Strategic Learning Capability: Through the Lens of Environmental Jolts

    ERIC Educational Resources Information Center

    Moon, Hanna; Lee, Chan

    2015-01-01

    Purpose: This paper aims to deepen the understanding of strategic learning through the lens of environmental jolts. Design/methodology/approach: Strategic learning is explained from the three paradigms of organizational learning. Findings: Organizational learning provides a firm foundation to develop and elaborate the concept of strategic learning…

  3. Strategic planning: the first step in the planning process.

    PubMed

    Gelinas, Marc A

    2003-01-01

    Strategic planning is a systematic process through which an organization builds commitment among key stakeholders to goals and priorities which are essential to its mission and vision, and responsive to the operating environment. Strategic planning is the first step in a comprehensive planning process that also includes business planning and implementation planning. If all three steps are carried out in sequence, strategic planning can be a very effective means of educating the stakeholders about where the cancer program is and where it is going, gaining support and commitment for the direction that the cancer program will take, and assuring that everyone's expectations can be managed effectively. Unfortunately, some organizations and cancer program leaders misunderstand the process. Too often, strategic planning is used as a stand-alone activity. This article will describe what strategic planning is, how it should smoothly lead into business planning and implementation planning, and how to avoid the pitfalls that sometimes arise during the strategic planning effort.

  4. The Role of Public Relations in a Successful Fund-Raising Campaign.

    ERIC Educational Resources Information Center

    Adams, Michael F.; Bumgardner, Larry G.

    1991-01-01

    Pepperdine University's (California) 1980s fund-raising campaign was designed to raise overall institutional visibility, establish an image of quality education, improve institutional image in the business community, increase fund-raising momentum, and raise significant money for immediate capital needs. Theme, staffing, and advertising were key…

  5. Achilles Tendon Loading During Heel-Raising and -Lowering Exercises

    PubMed Central

    Revak, Andrew; Diers, Keith; Kernozek, Thomas W.; Gheidi, Naghmeh; Olbrantz, Christina

    2017-01-01

    Context: Achilles tendinopathies are common injuries during sport participation, although men are more prone to Achilles tendon injuries than women. Heel-raising and -lowering exercises are typically suggested for Achilles tendon rehabilitation. Objective: To compare the estimated Achilles tendon loading variables and the ankle range of motion (ROM) using a musculoskeletal model during commonly performed heel-raising and -lowering exercises. Design: Controlled laboratory study. Setting: University biomechanics laboratory. Patients or Other Participants: Twenty-one healthy men (age = 21.59 ± 1.92 years, height = 178.22 ± 8.02 cm, mass = 75.81 ± 11.24 kg). Intervention(s): Each participant completed 4 exercises: seated heel raising and lowering, bilateral standing heel raising and lowering, bilateral heel raising and unilateral lowering, and unilateral heel raising and lowering. Main Outcome Measure(s): A repeated-measures multivariate analysis of variance (α = .05) was used to compare Achilles tendon stress, force, and strain and ankle ROM for each exercise. Kinematic data were recorded at 180 Hz with 15 motion-analysis cameras synchronized with kinetic data collected from a force platform sampled at 1800 Hz. These data were then entered in a musculoskeletal model to estimate force in the triceps surae. For each participant, we determined Achilles tendon stress by measuring cross-sectional images using ultrasound. Results: Peak Achilles tendon loading was lowest when performing the seated heel-raising and -lowering exercise and highest when performing the unilateral heel-raising and -lowering exercise. Loading was greater for the unilateral exercise or portions of the exercise that were performed unilaterally. Conclusions: Bilateral and seated exercises with less weight-bearing force resulted in less Achilles tendon loading. These exercises may serve as progressions during the rehabilitation process before full-body weight-bearing, unilateral exercises are

  6. Connecting the Learning Organization, Strategic Planning, and Public Relations.

    ERIC Educational Resources Information Center

    Thornton, Bill; Perreault, George

    2002-01-01

    Examines common perceptions about barriers to effective strategic planning in school districts. Argues that primary barrier to effective use of strategic planning in schools is the failure of educators to fully understand the strategic planning process itself. Discusses the components of a learning organization. Links learning organizations with…

  7. 75 FR 80850 - Development of Strategic Plan 2011-2015

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ... intended for use as LSC embarks on its planning process. LSC anticipates publishing a draft Strategic Plan... process to develop a Strategic Plan for the years 2011-2015. Toward that end, LSC is soliciting... strategic planning efforts. In addition, Among other sources, LSC is considering the guidance provided by...

  8. Newspaper reporting on child raising in Japan.

    PubMed

    Basnet, Narayan Bahadur; Kato, Hitoshi; Nakamura, Yoshihiro; Watanabe, Hiroshi; Igarashi, Takashi

    2004-04-01

    Study of child-raising issues published in newspapers is lacking. The purpose of this article is to determine the spectrum of issues associated with child raising based on a newspaper. We conducted a cross-sectional study of items related to children (aged <19 years) reported in a Japanese newspaper from July 1, 2001, to June 30, 2002. A total of 1287 child-related items were published. The percentages of reports regarding individual health, health-related issues, topics on two or more issues, and global child issues were 5.9%, 28.8%, 62.9%, and 2.4%, respectively. The most common singly reported issues from 446 items were on child play and recreation, welfare activities, security, child abuse, child death, sports, and parenting. These reports assist parents, families, nurses, pediatricians, and child care workers in providing information on healthy child raising.

  9. MnDOT Library strategic plan : final report.

    DOT National Transportation Integrated Search

    2017-06-01

    MnDOTs Senior Leadership asked MnDOT Library to develop a Strategic Plan that identifies and reviews the challenges facing the Library over the next five years to better address the evolving needs of the department and users. The strategic plan is...

  10. State of Tennessee strategic highway safety plan

    DOT National Transportation Integrated Search

    2007-08-01

    The State of Tennessee's Strategic Highway Safety Plan was developed by the Tennessee Strategic Highway Safety Committee with the goal of reaching a 10% fatality rate reduction, based on CY 2002 data, by the end of CY 2008, with a projected saving of...

  11. RoMo: An efficient strategy for functional mosaic analysis via stochastic Cre recombination and gene targeting in the ROSA26 locus.

    PubMed

    Movahedi, Kiavash; Wiegmann, Robert; De Vlaminck, Karen; Van Ginderachter, Jo A; Nikolaev, Viacheslav O

    2018-07-01

    Functional mosaic analysis allows for the direct comparison of mutant cells with differentially marked control cells in the same organism. While this offers a powerful approach for elucidating the role of specific genes or signalling pathways in cell populations of interest, genetic strategies for generating functional mosaicism remain challenging. We describe a novel and streamlined approach for functional mosaic analysis, which combines stochastic Cre/lox recombination with gene targeting in the ROSA26 locus. With the RoMo strategy a cell population of interest is randomly split into a cyan fluorescent and red fluorescent subset, of which the latter overexpresses a chosen transgene. To integrate this approach into high-throughput gene targeting initiatives, we developed a procedure that utilizes Gateway cloning for the generation of new targeting vectors. RoMo can be used for gain-of-function experiments or for altering signaling pathways in a mosaic fashion. To demonstrate this, we developed RoMo-dnGs mice, in which Cre-recombined red fluorescent cells co-express a dominant-negative Gs protein. RoMo-dnGs mice allowed us to inhibit G protein-coupled receptor activation in a fraction of cells, which could then be directly compared to differentially marked control cells in the same animal. We demonstrate how RoMo-dnGs mice can be used to obtain mosaicism in the brain and in peripheral organs for various cell types. RoMo offers an efficient new approach for functional mosaic analysis that extends the current toolbox and may reveal important new insights into in vivo gene function. © 2018 Wiley Periodicals, Inc.

  12. Strong Horses-Systems Thinking-Strategic Communication

    DTIC Science & Technology

    2009-04-30

    nature into how strategic leaders think about strategic communication prove salient when attempting to test the system with messages and actions...tools are equal nor found in each government agency. Those tools include but are not limited to: Information and Psychological operations (IO/PSYOP...25 Ludwig von Bertalanffy, General System Theory,1968. 26 Robert Lilienfeld , The Rise in System’s

  13. Unmasking the Capability of Strategic Learning: A Validation Study

    ERIC Educational Resources Information Center

    Siren, Charlotta A.

    2012-01-01

    Purpose: The strategic learning perspective has attracted increased interest among strategic management scholars, yet the operationalisation of this concept is still in its infancy. The aim of this study is to develop a multidimensional understanding of the strategic learning process and to build an instrument to measure this concept.…

  14. Strategic Planning and Open Learning: Turkey Tails and Frogs.

    ERIC Educational Resources Information Center

    Pacey, Lucille

    This paper discusses the principles of strategic planning and how they can be applied in open and distance learning for greater student success. The model selected for discussion is the Applied Strategic Planning Model which proposes nine important steps for strategic planning: planning to plan, values audit, mission formulation, strategic…

  15. Strategic communication related to academic performance: Evidence from China.

    PubMed

    Zhao, Li; Chen, Lulu; He, Luwei; Heyman, Gail D

    2017-09-01

    We examined a range of forms of strategic communication relevant to academic performance among 151 seventh- and eleventh-grade adolescents in China. Participants were asked to rate the frequency of their engagement of strategic communication and to evaluate the possible motives for each strategy. The most commonly adopted strategy was to give a vague response about one's own performance, and the predominant motives for strategic communication were the desires to outcompete others, to be prosocial, and to be modest. Males were more likely than females to focus on gaining social approval, and eleventh graders were more likely than seventh graders to focus on being prosocial and modest when engaging in strategic communication. These findings provide insight into the development of strategic communication beyond Western culture. Statement of contribution What is already known on this subject? Adolescents in the West often hide their effort to appear more competent or to gain social acceptance. Little is known about other communication strategies related to academic performance. Little is known about the development of these strategies in non-Western samples. What does this study add? We show that in China, as in Western cultures, children often engage in strategic communication. We demonstrate links between different forms of strategic communication and specific motives. We demonstrate that strategic communication can be motivated by outcompeting others, by being prosocial, and by being modest. © 2017 The British Psychological Society.

  16. VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease

    PubMed Central

    An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid

    2016-01-01

    CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297

  17. Conservation of Strategic Aerospace Materials (COSAM)

    NASA Technical Reports Server (NTRS)

    Stephens, J. R.

    1981-01-01

    Research efforts to reduce the dependence of the aerospace industry on strategic metals, such as cobalt (Co), columbium (Cb), tantalum (Ta), and chromium (Cr), by providing the materials technology needed to minimize the strategic metal content of critical aerospace components for gas turbine engines are addressed. Thrusts in three technology areas are identified: near term activities in the area of strategic element substitution; intermediate-range activities in the area of materials processing; and long term, high risk activities in the area of 'new classes' of high temprature metallic materials. Specifically, the role of cobalt in nickel-base and cobalt-base superalloys vital to the aerospace industry is examined along with the mechanical and physical properties of intermetallics that will contain a minimum of the stragetic metals.

  18. Comprehensive U.S. Government Strategic Communication Policy: The Way Forward

    DTIC Science & Technology

    2009-06-12

    franchised cell. It costs little, is easy to distribute, and has near- immediate worldwide impact. (White 2007) The Smith-Mundt Act The historical...lack of ability to communicate strategically. The United States‘ strategic communication failure has cost the country friends and allies, and it...to communicate strategically. The United States‘ strategic communication failure has cost the country friends and allies, and it also hurts the

  19. Strategic Thinking: The Untapped Resource for Leaders.

    ERIC Educational Resources Information Center

    Alfred, Richard L.

    2001-01-01

    Strategic thinking is an organized, analytical process by which college leaders can assess: (1) existing and potential competitors; (2) sources of competitive advantage; and (3) college capabilities and competitive position. Three outcomes of strategic thinking are: (1) clear institutional strategy and direction; (2) improved institutional…

  20. Teaching Strategic Management with a Business Game.

    ERIC Educational Resources Information Center

    Knotts, Ulysses S., Jr.; Keys, J. Bernard

    1997-01-01

    Management games are increasingly used to teaching strategic management by integrating functional areas of business and providing a working knowledge of the strategic management process. This article summarizes the experience of two veteran instructors, presenting course learning objectives, game pedagogy, team organization and management, game…

  1. Strategic planning in an academic radiation medicine program.

    PubMed

    Hamilton, J L; Foxcroft, S; Moyo, E; Cooke-Lauder, J; Spence, T; Zahedi, P; Bezjak, A; Jaffray, D; Lam, C; Létourneau, D; Milosevic, M; Tsang, R; Wong, R; Liu, F F

    2017-12-01

    In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp) at the Princess Margaret Cancer Centre. The rmp conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations.

  2. Strategic Staffing

    ERIC Educational Resources Information Center

    Clark, Ann B.

    2012-01-01

    Business and industry leaders do not flinch at the idea of placing top talent in struggling departments and divisions. This is not always the case in public education. The Charlotte-Mecklenburg Schools made a bold statement to its community in its strategic plan by identifying two key reform levers--(1) an effective principal leading each school;…

  3. Leveraging strategic planning for improved financial performance.

    PubMed

    Zuckerman, A

    2000-12-01

    Healthcare providers increasingly are relying on strategic planning to guide the allocation of capital and other resources. Strategic planning helps identify and prioritize opportunities for financial improvement, particularly revenue-generating initiatives, which offer the greatest opportunity for significant long-term benefits. New revenue usually can be generated in one of five ways: increase market share, expand service area, fill gaps in the continuum of services, develop niche services where needed in the service area, and repackage existing services to address specific market segments. Once a strategic plan is implemented, it should be reviewed periodically and modified as necessary.

  4. Conceptualizing strategic environmental assessment: Principles, approaches and research directions

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

    Noble, Bram, E-mail: b.noble@usask.ca; Nwanekezie, Kelechi

    Increasing emphasis has been placed in recent years on transitioning strategic environmental assessment (SEA) away from its environmental impact assessment (EIA) roots. Scholars have argued the need to conceptualize SEA as a process designed to facilitate strategic thinking, thus enabling transitions toward sustainability. The practice of SEA, however, remains deeply rooted in the EIA tradition and scholars and practitioners often appear divided on the nature and purpose of SEA. This paper revisits the strategic principles of SEA and conceptualizes SEA as a multi-faceted and multi-dimensional assessment process. It is suggested that SEA can be conceptualized as series of approaches operatingmore » along a spectrum from less to more strategic – from impact assessment-based to strategy-based – with each approach to SEA differentiated by the specific objectives of SEA application and the extent to which strategic principles are reflected in its design and implementation. Advancing the effectiveness of SEA requires a continued research agenda focused on improving the traditional SEA approach, as a tool to assess the impacts of policies, plans and programs (PPPs). Realizing the full potential of SEA, however, requires a new research agenda — one focused on the development and testing of a deliberative governance approach to SEA that can facilitate strategic innovations in PPP formulation and drive transitions in short-term policy and initiatives based on longer-term thinking. - Highlights: • SEA facilitates strategic thinking, enabling transitions toward sustainability. • SEA is conceptualized as a spectrum of approaches, from IA-based to strategy-based. • Each approach variably emphasizes strategic principles in its design and practice. • There is no one conceptualization of SEA that is best, SEA is fit for PPP purpose. • Research is needed to advance SEA to facilitate strategic PPP transformations.« less

  5. The strategic use of outcome information.

    PubMed

    Thompson, D I; Sirio, C; Holt, P

    2000-10-01

    Most health care executives see outcome measurement as a technical or tactical matter rather than as a strategic tool. Accordingly, provider investment in outcome measurement and management is relatively small. Nevertheless, outcome information can be key to achieving an organization's strategic objectives. Advances in risk adjustment and improvements in technology for data collection and analysis have made outcome measurement a practical tool for individual hospital use. Strategically integrated outcome measurement efforts can give providers a competitive advantage over organizations that only use outcomes tactically. One of the best examples of an acute care provider that has used outcome information for strategic advantage is Intermountain Health Care (IHC; Salt Lake City). In 1997 IHC made clinical quality and outcomes the primary focus of its five-year strategic plan. To support the new strategy IHC's board of trustees approved the development of an outcome information system that generated data along clinical processes of care and the creation of a new management structure to use these data to hold professionals accountable and to set and achieve clinical improvement goals. From 1996 to 1999, IHC's share of the commercial health care market in Utah increased from roughly 50% to about 62% of the market, with the result that it has stopped actively marketing its services. Health care executives will not willingly invest in outcomes until they believe that they have business value. Therefore, making the business case for outcomes can help improve the quality of health care and the lives of individuals.

  6. Strategic Planning for Educational Reform and Improvement.

    ERIC Educational Resources Information Center

    D'Amico, Joseph J.

    1988-01-01

    Defines strategic planning, outlines its key elements and activities, and summarizes the difficulties of applying a top-down, profit-driven process to education. Explains Strategic Planning for Educational Reform and Improvement (SPERI), a set of manageable, concise procedures for top school administrators. Describes SPERI applications in an…

  7. 7 CFR 65.235 - Raised.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Raised. 65.235 Section 65.235 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL...

  8. Measuring strategic success.

    PubMed

    Gish, Ryan

    2002-08-01

    Strategic triggers and metrics help healthcare providers achieve financial success. Metrics help assess progress toward long-term goals. Triggers signal market changes requiring a change in strategy. All metrics may not move in concert. Organizations need to identify indicators, monitor performance.

  9. Decoupling the use and meaning of strategic plans in public healthcare

    PubMed Central

    2013-01-01

    Background The culture of New Public Management has promoted the diffusion of strategic management tools throughout Public Healthcare Organisations (PHOs). There is consensus that better strategic planning tools are required to achieve higher levels of organisational performance. This paper provides evidence and understanding of the emergent uses and scope of strategic planning in PHOs, in order to answer three research questions: (i) has the New Public Management approach changed the organisational culture of PHOs in terms of how they adopt, diffuse, and use strategic planning documents? (ii) how coherent are strategic planning documents in PHOs? and (iii) what are the main purposes of strategic documents in PHOs? Methods An analysis was carried out in three Italian Local Health Authorities. We analysed the number and types of formal strategic documents adopted between 2004 and 2012, evaluating their degree of coherence and coordination, their hierarchy, their degree of disclosure, and the consistency of their strategic goals. A content analysis was performed to investigate overlap in terms of content and focus, and a qualitative analysis was carried out to study and represent the relationships between documents. Results The analysis showed that a rich set of strategic documents were adopted by each PHO. However, these are often uncoordinated and overlap in terms of content. They adopt different language and formats for various stakeholders. The presence of diverse external drivers may explain the divergent focus, priorities and inconsistent goals in the strategic documents. This planning complexity makes it difficult to determine how the overall goals and mission of an organisation are defined and made visible. Conclusions The evidence suggests that PHOs use a considerable number of strategic documents. However, they employ no clear or explicit overarching strategy currently, and strategic planning appears to be externally oriented. All the documents communicate

  10. Decoupling the use and meaning of strategic plans in public healthcare.

    PubMed

    Lega, Federico; Longo, Francesco; Rotolo, Andrea

    2013-01-04

    The culture of New Public Management has promoted the diffusion of strategic management tools throughout Public Healthcare Organisations (PHOs). There is consensus that better strategic planning tools are required to achieve higher levels of organisational performance. This paper provides evidence and understanding of the emergent uses and scope of strategic planning in PHOs, in order to answer three research questions: (i) has the New Public Management approach changed the organisational culture of PHOs in terms of how they adopt, diffuse, and use strategic planning documents? (ii) how coherent are strategic planning documents in PHOs? and (iii) what are the main purposes of strategic documents in PHOs? An analysis was carried out in three Italian Local Health Authorities. We analysed the number and types of formal strategic documents adopted between 2004 and 2012, evaluating their degree of coherence and coordination, their hierarchy, their degree of disclosure, and the consistency of their strategic goals. A content analysis was performed to investigate overlap in terms of content and focus, and a qualitative analysis was carried out to study and represent the relationships between documents. The analysis showed that a rich set of strategic documents were adopted by each PHO. However, these are often uncoordinated and overlap in terms of content. They adopt different language and formats for various stakeholders. The presence of diverse external drivers may explain the divergent focus, priorities and inconsistent goals in the strategic documents. This planning complexity makes it difficult to determine how the overall goals and mission of an organisation are defined and made visible. The evidence suggests that PHOs use a considerable number of strategic documents. However, they employ no clear or explicit overarching strategy currently, and strategic planning appears to be externally oriented. All the documents communicate similar topics to different

  11. Rethinking schools of public health: a strategic alliance model.

    PubMed

    Moloughney, Brent W; Skinner, Harvey A

    2006-01-01

    Canada is in the midst of rejuvenation of public health organizations, mandates and infrastructure. Major planning exercises are underway regarding public health human resources, where academic institutions have a key role to play. To what extent could schools of public health be part of the solution? Many universities across Canada are considering or in the process of implementing MPH programs (some 17 programs planned and/or underway) and possible schools of public health. However, concerns are raised about critical mass, quality and standards. We encourage innovation and debate about ways to enhance collaborative and structural arrangements for education programs. A school of public health model might emerge from this, but so too might other models. Also, novel types of organizational structure need consideration. One example is a "strategic alliance" model that is broad-based, integrative and adaptive--building on the interdisciplinary focus needed for addressing public health concerns in the 21st century. From our perspective, the central question is: what (new) types of organizational structures and, equally important, collaborative networks will enable Canada to strengthen its public health workforce so that it may better address local and global challenges to public health?

  12. Strategic plan for infrastructure optimization

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

    Donley, C.D.

    This document represents Fluor Daniel Hanford`s and DynCorp`s Tri-Cities Strategic Plan for Fiscal Years 1998--2002, the road map that will guide them into the next century and their sixth year of providing safe and cost effective infrastructure services and support to the Department of Energy (DOE) and the Hanford Site. The Plan responds directly to the issues raised in the FDH/DOE Critical Self Assessment specifically: (1) a strategy in place to give DOE the management (systems) and physical infrastructure for the future; (2) dealing with the barriers that exist to making change; and (3) a plan to right-size the infrastructuremore » and services, and reduce the cost of providing services. The Plan incorporates initiatives from several studies conducted in Fiscal Year 1997 to include: the Systems Functional Analysis, 200 Area Water Commercial Practices Plan, $ million Originated Cost Budget Achievement Plan, the 1OO Area Vacate Plan, the Railroad Shutdown Plan, as well as recommendations from the recently completed Review of Hanford Electrical Utility. These and other initiatives identified over the next five years will result in significant improvements in efficiency, allowing a greater portion of the infrastructure budget to be applied to Site cleanup. The Plan outlines a planning and management process that defines infrastructure services and structure by linking site technical base line data and customer requirements to work scope and resources. The Plan also provides a vision of where Site infrastructure is going and specific initiatives to get there.« less

  13. Building a team through a strategic planning process.

    PubMed

    Albert, Debra; Priganc, Dave

    2014-01-01

    Strategic planning is a process often left to senior hospital leadership, with limited input from unit-level, bedside patient care providers. This frequent approach to strategic planning misses the opportunity to engage a wide range of employees, build a shared sense of commitment, produce a collaborative team environment, and to generate greater acceptance of the plan. The Patient Care Services division at the University of Chicago Medicine used a strategic planning process that incorporated 360-degree input from both within the Patient Care Services division and outside of the division. The result is a strategic vision and plan that, shaped by broad-based input from both internal and external constituencies, is strengthened by the team that emerged from the process. Through the process of identifying a common understanding of the group's future direction, a shared purpose was created that transcended traditional professional boundaries and shaped a cohesive team focused on effective and efficient patient care. Now, with a focused strategic plan and a team centered on a shared purpose, the team is beginning to effectively deliver on the plan.

  14. Molecular characterization and analysis of the acrB gene of Aspergillus nidulans: a gene identified by genetic interaction as a component of the regulatory network that includes the CreB deubiquitination enzyme.

    PubMed Central

    Boase, Natasha A; Lockington, Robin A; Adams, Julian R J; Rodbourn, Louise; Kelly, Joan M

    2003-01-01

    Mutations in the acrB gene, which were originally selected through their resistance to acriflavine, also result in reduced growth on a range of sole carbon sources, including fructose, cellobiose, raffinose, and starch, and reduced utilization of omega-amino acids, including GABA and beta-alanine, as sole carbon and nitrogen sources. The acrB2 mutation suppresses the phenotypic effects of mutations in the creB gene that encodes a regulatory deubiquitinating enzyme, and in the creC gene that encodes a WD40-repeat-containing protein. Thus AcrB interacts with a regulatory network controlling carbon source utilization that involves ubiquitination and deubiquitination. The acrB gene was cloned and physically analyzed, and it encodes a novel protein that contains three putative transmembrane domains and a coiled-coil region. AcrB may play a role in the ubiquitination aspect of this regulatory network. PMID:12750323

  15. 30 CFR 56.14211 - Blocking equipment in a raised position.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... raised position. (a) Persons shall not work on top of, under, or work from mobile equipment in a raised... accidentally. (b) Persons shall not work on top of, under, or work from a raised component of mobile equipment... prevent accidental lowering when persons are working on or around mobile equipment and are exposed to the...

  16. Fosmid Cre-LoxP Inverse PCR Paired-End (Fosmid CLIP-PE), a Novel Method for Constructing Fosmid Pair-End Library (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

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

    Peng, Ze

    2012-06-01

    Ze Peng from DOE JGI presents "Fosmid Cre-LoxP Inverse PCR Paired-End (Fosmid CLIP-PE), a Novel Method for Constructing Fosmid Pair-End Library" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  17. Fosmid Cre-LoxP Inverse PCR Paired-End (Fosmid CLIP-PE), a Novel Method for Constructing Fosmid Pair-End Library (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    Peng, Ze

    2018-01-24

    Ze Peng from DOE JGI presents "Fosmid Cre-LoxP Inverse PCR Paired-End (Fosmid CLIP-PE), a Novel Method for Constructing Fosmid Pair-End Library" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  18. Long-Range Strategic Planning: The Rochester Experience.

    ERIC Educational Resources Information Center

    Schultz, John M.; Anthony, Deborah L.

    The administration of Rochester Community Schools (Michigan) initiated a process for long-range strategic planning in 1984, described in this synopsis. Strategic planning is an ongoing, evolutionary process of defining the business one is in or should be in; establishing organizational goals and objectives; and developing and implementing…

  19. SSC San Diego Strategic Plan. Revision 1

    DTIC Science & Technology

    1998-04-01

    information dominance . This Strategic Plan is SSC San Diego’s blueprint to meet that challenge. The plan is both a vehicle for carrying us into the...provider of integrated C4ISR solutions for warrior information dominance - is our enduring goal. Our plan specifies five long-range strategic

  20. Using Strategic Planning To Improve Rural Schools.

    ERIC Educational Resources Information Center

    D'Amico, Joseph J.

    This paper describes the elements of strategic planning and applies them to educational reform and improvement. The paper also describes how a planning model, Strategic Planning for Educational Reform and Improvement (SPERI), was used by Rural Assistance Councils (RACs) in Pennsylvania and Delaware, with technical assistance from Research for…

  1. Developing Strategic Planning for the Retail Market.

    ERIC Educational Resources Information Center

    Greenawalt, Richard A.

    1983-01-01

    Retailers need a strategic plan that will enable them to adapt to changing trends and work with new ideas. Questions retailers should ask to shape the strategic plan and generic strategies--overall cost leadership, differentiation, and marketing to a particular group or offering a special service--are discussed. (SR)

  2. Strategic Retrieval in a Reality Monitoring Task

    ERIC Educational Resources Information Center

    Rosburg, Timm; Mecklinger, Axel; Johansson, Mikael

    2011-01-01

    Strategic recollection refers to control processes that allow the retrieval of information that is relevant for a specific situation. These processes can be studied in memory exclusion tasks, which require the retrieval of particular kinds of episodic information. In the current study, we investigated strategic recollection in reality monitoring…

  3. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

    PubMed

    do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

    2011-05-01

    Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

  4. FY16-20 Strategic Plan.

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

    Harwell, Amber Suzanne

    2015-07-01

    Welcome to our FY16–FY20 Strategic Plan, which both refects our continued dedication to the work we do and reinforces the importance of the integrated Laboratories’ strategic framework to our future. This document is the result of the leadership team’s journey over the past few years in response to the needs of our nation. In an external environment that continues to change, sometimes in unexpected ways, it is critical that our mission areas and our foundation become increasingly synergistic, forming a whole whose parts are interdependent.

  5. A Handbook for Strategic Planning

    DTIC Science & Technology

    1994-01-01

    sale; its / 94 dig Is Ulc and Uindo Al. 10oherty, *q** 3 About the TQL Office I ie mission of the Total Quality Leadership 0 QL) Office, Office of the...Strategic Planning DeieL. Wells u.1da M4. Doherty. Ph.D. NI.gpOpmwHG CRA141ZAM01 NAME() AN4D A060111(li; L. PINORUMU4OGNIZAMSN Total Qu~ality Leadership ...Total Quality Leadership , 48 mtrategic direction, strategic intent, organizational planning, 11tinaiCMc MIisiing.mysteusth nking, gap analysis 17 1CUPMtlI

  6. Strategic planning in an academic radiation medicine program

    PubMed Central

    Hamilton, J.L.; Foxcroft, S.; Moyo, E.; Cooke-Lauder, J.; Spence, T.; Zahedi, P.; Bezjak, A.; Jaffray, D.; Lam, C.; Létourneau, D.; Milosevic, M.; Tsang, R.; Wong, R.; Liu, F.F.

    2017-01-01

    Background In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp) at the Princess Margaret Cancer Centre. The rmp conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. Methods Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. Results The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. Conclusions The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations. PMID:29270061

  7. The Campus Green: Fund Raising in Higher Education. ERIC Digest.

    ERIC Educational Resources Information Center

    Brittingham, Barbara E.; Pezzullo, Thomas R.

    This digest summarizes issues raised in a research report on fund raising in higher education. The following questions are addressed: What are the changes and trends since the early days of educational fund raising? What are the implications? What is known about spending? What is known about donor behavior? What are the major ethical issues? What…

  8. Strategic Decision to Utilize Abu Ghraib

    DTIC Science & Technology

    2012-03-22

    manuscript is submitted in partial fulfillment of the requirements of the Master of Strategic Studies Degree. The views expressed in this student academic...submitted in partial fulfillment of the requirements of the Master of Strategic Studies Degree. The U.S. Army War College is accredited by the Commission...operations. Endnotes 1 Catharine MacKinnon, ― Feminism Unmodified: Discourses on Life and Law,‖ 1987, http://www.brainyquote.com/quotes

  9. SSC San Diego Strategic Plan. Revision 2

    DTIC Science & Technology

    2000-05-01

    information dominance . This Strategic Plan is SSC San Diego’s blueprint to meet that challenge. The plan is both a vehicle for carrying us into the...provider of integrated C4ISR solutions for warrior information dominance is our enduring goal. Our plan specifies five long-range strategic objectives. SSC

  10. The first powerful steps in strategic development.

    PubMed

    Chang, Y N; Platt, W

    1986-11-01

    In an ever-changing business climate, the need for strategically oriented management increases, for the organization that is insensitive and unresponsive to its environment will not survive. The authors of this "Action Plan" examine the challenges facing the health industry and outline a series of actions for initiating strategic-driven management.

  11. Strategic plan creates a blueprint for budgeting.

    PubMed

    Cook, D

    1990-05-01

    Effective healthcare organizations develop budgets that reflect and support a strategic plan. Senior managers set a framework that expresses the hospital's future strategic objectives. The budget enables executives to determine which specific service lines are profitable or unprofitable. Administrators and clinicians at all levels are involved in the budgeting process.

  12. Information Technology (IT) Strategic Alignment: A Correlational Study between the Impact of IT Governance Structures and IT Strategic Alignment

    ERIC Educational Resources Information Center

    Asante, Keith K.

    2010-01-01

    This dissertation explored the extent to which Information Technology (IT) strategic alignment are impacted by IT governance structures. The study discusses several strategic alignment and IT governance literature that presents a gap in the literature domain. Subsequent studies researched issues surrounding why organizations are not able to align…

  13. Robinson Rancheria Strategic Energy Plan; Middletown Rancheria Strategic Energy Plan, Scotts Valley Rancheria Strategic Energy Plan, Elem Indian Colony Strategic Energy Plan, Upperlake Rancheria Strategic Energy Plan, Big Valley Rancheria Strategic Energy Plan

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

    McGinnis and Associates LLC

    2008-08-01

    The Scotts Valley Band of Pomo Indians is located in Lake County in Northern California. Similar to the other five federally recognized Indian Tribes in Lake County participating in this project, Scotts Valley Band of Pomo Indians members are challenged by generally increasing energy costs and undeveloped local energy resources. Currently, Tribal decision makers lack sufficient information to make informed decisions about potential renewable energy resources. To meet this challenge efficiently, the Tribes have committed to the Lake County Tribal Energy Program, a multi Tribal program to be based at the Robinson Rancheria and including The Elem Indian Colony, Bigmore » Valley Rancheria, Middletown Rancheria, Habematolel Pomo of Upper Lake and the Scotts Valley Pomo Tribe. The mission of this program is to promote Tribal energy efficiency and create employment opportunities and economic opportunities on Tribal Lands through energy resource and energy efficiency development. This program will establish a comprehensive energy strategic plan for the Tribes based on Tribal specific plans that capture economic and environmental benefits while continuing to respect Tribal cultural practices and traditions. The goal is to understand current and future energy consumption and develop both regional and Tribe specific strategic energy plans, including action plans, to clearly identify the energy options for each Tribe.« less

  14. The Science of Strategic Communication | Science Inventory ...

    EPA Pesticide Factsheets

    The field of Strategic Communication involves a focused effort to identify, develop, and present multiple types of communication media on a given subject. A Strategic Communication program recognizes the limitations of the most common communication models (primarily “one size fits all” and “presenting everything and letting the audience decide what is important”) and specifically focuses on building a communication framework that is composed of three interlinked pillars: (1) Message – Identifying the right content for a given audience and a vehicle, (2) Audience – Identify the right target group for a given message and vehicle, (3) Vehicle – Identifying the right types of media for a given message and audience. In addition to serving as an organizational framework, the physical structure of a Strategic Communication plan also can serve as a way to show an audience where they, the message, and vehicle fit into the larger picture (i.e., “you are here”). This presentation explores the tenets of Strategic Communication and its use in natural resources management as it relates to advancing restoration activities in the Greater Everglades. This presentation is aimed at restoration practitioners and decision makers. This presentation provides an introduction to the field of strategic communication and presents a generalizable framework for use in the natural sciences. The presentation also gives an example of a communication implementation matrix,

  15. A Comparative, Holistic, Multiple-Case Study of the Implementation of the Strategic Thinking Protocol© and Traditional Strategic Planning Processes at a Southeastern University

    ERIC Educational Resources Information Center

    Robinson, Deborah J.

    2012-01-01

    This study explores the strategic thinking and strategic planning efforts in a department, college and university in the Southeastern United States. The goal of the study was to identify elements of strategic planning processes that meet the unique organizational features and complexities of a higher education institution. The study employed a…

  16. Comparative Strategic Cultures Curriculum Project: Assessing Strategic Culture as a Methodological Approach to Understanding WMD Decision-Making by States and Non-State Actors

    DTIC Science & Technology

    2006-10-31

    International Security and Arms Control;: Stanford University Press, 1994. Lin, Chong-Pin. China’s Nuclear Weapons Strategy : Tradition within Evolution ...analysts tend to posit interests, emphasize strategic interaction , and discount bureaucratic influence. - Paul DiMaggio, “Culture and Cognition...Additional Sources - Henry Rowen, "The Evolution of Strategic Nuclear Doctrine," in Laurence Martin, ed., Strategic Thought in the Nuclear Age

  17. 15 CFR 1160.22 - Goal of the Strategic Partnership initiative.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INNOVATION Strategic Partnership Initiative § 1160.22 Goal of the Strategic Partnership initiative. (a) This... the innovation activities for a broad range of applications made possible by that technology. The... precompetitive stage of innovation. In contrast, Strategic Partnerships are made up generally of noncompeting...

  18. 15 CFR 1160.22 - Goal of the Strategic Partnership initiative.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INNOVATION Strategic Partnership Initiative § 1160.22 Goal of the Strategic Partnership initiative. (a) This... the innovation activities for a broad range of applications made possible by that technology. The... precompetitive stage of innovation. In contrast, Strategic Partnerships are made up generally of noncompeting...

  19. 15 CFR 1160.22 - Goal of the Strategic Partnership initiative.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INNOVATION Strategic Partnership Initiative § 1160.22 Goal of the Strategic Partnership initiative. (a) This... the innovation activities for a broad range of applications made possible by that technology. The... precompetitive stage of innovation. In contrast, Strategic Partnerships are made up generally of noncompeting...

  20. Applying Mixed Methods Techniques in Strategic Planning

    ERIC Educational Resources Information Center

    Voorhees, Richard A.

    2008-01-01

    In its most basic form, strategic planning is a process of anticipating change, identifying new opportunities, and executing strategy. The use of mixed methods, blending quantitative and qualitative analytical techniques and data, in the process of assembling a strategic plan can help to ensure a successful outcome. In this article, the author…