Radiation-induced leukemia: Comparative studies in mouse and man. Annual performance report, June 1, 1991--October 31, 1991

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

Haas, M.

1991-12-31

We now have a clear understanding of the mechanism by which radiation-induced (T-cell) leukemia occurs. In irradiated mice (radiation-induced thymic leukemia) and in man (acute lymphoblastic T-cell leukemia, T-ALL) the mechanism of leukemogenesis is surprisingly similar. Expressed in the most elementary terms, T-cell leukemia occurs when T-cell differentiation is inhibited by a mutation, and pre-T cells attempt but fail to differentiate in the thymus. Instead of leaving the thymus for the periphery as functional T-cells they continue to proliferate in the thymus. The proliferating pre- (pro-) T-cells constitute the (early) acute T-cell leukemia (A-TCL). This model for the mechanism ofmore » T-cell leukemogenesis accounts for all the properties of both murine and human A-TCL. Important support for the model has recently come from work by Ilan Kirsch and others, who have shown that mutations/deletions in the genes SCL (TAL), SIL, and LCK constitute primary events in the development of T-ALL, by inhibiting differentiation of thymic pre- (pro-) T-cells. This mechanism of T-cell leukemogenesis brings several specific questions into focus: How do early A-TCL cells progress to become potently tumorigenic and poorly treatable? Is it feasible to genetically suppress early and/or progressed A-TCL cells? What is the mechanism by which the differentiation-inhibited (leukemic) pre-T cells proliferate? During the first grant year we have worked on aspects of all three questions.« less

Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells.

PubMed

Watanabe, Toshiki

2017-03-02

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor-NF-κB signaling such as PLCG1 , PRKCB , and CARD11 and gain-of function mutations in CCR4 and CCR7 Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-κB. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1-infected CD4 + T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemogenesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated. © 2017 by The American Society of Hematology.

Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia

USDA-ARS?s Scientific Manuscript database

TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine, possibly leading to loss of DNA methylation. TET2 mutations are common in myeloid leukemia and were proposed to contribute to leukemogenesis through DNA methylation. To expand on this concept, we studied chronic myelomonocyti...

Scientist | Center for Cancer Research

Cancer.gov

KEY ROLES/RESPONSIBILITIES The Scientist I will support research efforts to define the role of transcriptional regulators in myeloid cell development, and their potential role in leukemogenesis.  This work will be accomplished performing both molecular and stem cell biology techniques, cloning and construction of retroviral vectors, quantitative RT-PCR, cloning of conditional

A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia.

PubMed

Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

2014-04-10

Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, we demonstrate that both 3q rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. Genomic excision of the ectopic enhancer restored EVI1 silencing and led to growth inhibition and differentiation of AML cells, which could be replicated by pharmacologic BET inhibition. Our data show that structural rearrangements involving the chromosomal repositioning of a single enhancer can cause deregulation of two unrelated distal genes, with cancer as the outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

[Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial].

PubMed

Chen, Sai-Juan; Chen, Li-Juan; Zhou, Guang-Biao

2005-02-01

In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival time. With the median survival of 18 months, none of the 20 cases in combination treatment relapsed, whereas 7 relapsed in 37 cases in mono-treatment. This is the best clinical effect achieved in treating adult acute leukemia to this day, possibly making APL the first adult curable leukemia. Based on the great success of the pathogenetic gene target therapy in APL, this strategy may extend to other leukemias. Combination of Gleevec and arsenic agents in treating chronic myeloid leukemia has already make a figure both in clinical and laboratory research, aiming at counteracting the abnormal tyrosine kinase activity of ABL and the degradating BCR-ABL fusion protein. In acute myeloid leukemia M(2b), using new target therapy degradating AML1-ETO fusion protein and reducing the abnormal tyrosine kinase activity of c-kit will also lead to new therapeutic management in acute leukemias.

Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation

USDA-ARS?s Scientific Manuscript database

PU.1 transcription factor is a critical regulator of hematopoiesis and leukemogenesis. Because PU.1 interacts with transcription factors GATA-2 and C/EBPa, both of which are involved in the regulation of adipogenesis, we investigated whether PU.1 also plays a role in the regulation of adipocyte diff...

CHEMICAL AND RADIATION LEUKEMOGENESIS IN HUMANS AND RODENTS AND THE VALUE OF RODENT MODELS FOR ASSESSING RISKS OF LYMPHOHEMATOPOIETIC CANCERS

EPA Science Inventory

This report is intended to provide an up-to-date overview of the lymphoid and hematopoietic diseases induced in humans and rodents following exposure to chemical agents. It includes a brief introduction to hematopoiesis and leukemia-inducing agents and their effects in mice and r...

Vitamin C: C-ing a New Way to Fight Leukemia.

PubMed

Schönberger, Katharina; Cabezas-Wallscheid, Nina

2017-11-02

Metabolic cues and (epi-)genetic factors are emerging regulators of hematopoietic stem cell (HSC) potency. Two new studies in Nature and Cell, from Agathocleous et al. (2017) and Cimmino et al. (2017), respectively, show that vitamin C regulates HSC function and suppresses leukemogenesis by modulating Tet2 activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Leukemogenesis Induced by an Activating β-catenin mutation in Osteoblasts

PubMed Central

Kode, Aruna; Manavalan, John S.; Mosialou, Ioanna; Bhagat, Govind; Rathinam, Chozha V.; Luo, Na; Khiabanian, Hossein; Lee, Albert; Vundavalli, Murty; Friedman, Richard; Brum, Andrea; Park, David; Galili, Naomi; Mukherjee, Siddhartha; Teruya-Feldstein, Julie; Raza, Azra; Rabadan, Raul; Berman, Ellin; Kousteni, Stavroula

2014-01-01

Summary Cells of the osteoblast lineage affect homing, 1, 2 number of long term repopulating hematopoietic stem cells (HSCs) 3, 4, HSC mobilization and lineage determination and B lymphopoiesis 5-8. More recently osteoblasts were implicated in pre-leukemic conditions in mice 9, 10. Yet, it has not been shown that a single genetic event taking place in osteoblasts can induce leukemogenesis. We show here that in mice, an activating mutation of β-catenin in osteoblasts alters the differentiation potential of myeloid and lymphoid progenitors leading to development of acute myeloid leukemia (AML) with common chromosomal aberrations and cell autonomous progression. Activated β-catenin stimulates expression of the Notch ligand Jagged-1 in osteoblasts. Subsequent activation of Notch signaling in HSC progenitors induces the malignant changes. Demonstrating the pathogenetic role of the Notch pathway, genetic or pharmacological inhibition of Notch signaling ameliorates AML. Nuclear accumulation and increased β-catenin signaling in osteoblasts was also identified in 38% of patients with MDS/AML. These patients showed increased Notch signaling in hematopoietic cells. These findings demonstrate that genetic alterations in osteoblasts can induce AML, identify molecular signals leading to this transformation and suggest a potential novel pharmacotherapeutic approach to AML. PMID:24429522

Down syndrome and leukemia: insights into leukemogenesis and translational targets

PubMed Central

Barbaric, Draga; Byatt, Sally-Anne; Sutton, Rosemary; Marshall, Glenn M.

2015-01-01

Children with Down syndrome (DS) have a significantly increased risk of childhood leukemia, in particular acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (DS-ALL). A pre-leukemia, called transient myeloproliferative disorder (TMD), characterised by a GATA binding protein 1 (GATA1) mutation, affects up to 30% of newborns with DS. In most cases, the pre-leukemia regresses spontaneously, however one-quarter of these children will go on to develop AMKL or myelodysplastic syndrome (MDS) . AMKL and MDS occurring in young children with DS and a GATA1 somatic mutation are collectively termed myeloid leukemia of Down syndrome (ML-DS). This model represents an important multi-step process of leukemogenesis, and further study is required to identify therapeutic targets to potentially prevent development of leukemia. DS-ALL is a high-risk leukemia and mutations in the JAK-STAT pathway are frequently observed. JAK inhibitors may improve outcome for this type of leukemia. Genetic and epigenetic studies have revealed likely candidate drivers involved in development of ML-DS and DS-ALL. Overall this review aims to identify potential impacts of new research on how we manage children with DS, pre-leukemia and leukemia. PMID:26835364

The transcriptional landscape of hematopoietic stem cell ontogeny

PubMed Central

McKinney-Freeman, Shannon; Cahan, Patrick; Li, Hu; Lacadie, Scott A.; Huang, Hsuan-Ting; Curran, Matthew; Loewer, Sabine; Naveiras, Olaia; Kathrein, Katie L.; Konantz, Martina; Langdon, Erin M.; Lengerke, Claudia; Zon, Leonard I.; Collins, James J.; Daley, George Q.

2012-01-01

Transcriptome analysis of adult hematopoietic stem cells (HSC) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSC purified from >2500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knock-down in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSC, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource (http://hsc.hms.harvard.edu) will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification. PMID:23122293

Excess congenital non-synonymous variation in leukemia-associated genes in MLL− infant leukemia: a Children's Oncology Group report

PubMed Central

Valentine, M C; Linabery, A M; Chasnoff, S; Hughes, A E O; Mallaney, C; Sanchez, N; Giacalone, J; Heerema, N A; Hilden, J M; Spector, L G; Ross, J A; Druley, T E

2014-01-01

Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. Although most cases are accompanied by MLL rearrangements and harbor very few somatic mutations, less is known about the genetics of the cases without MLL translocations. We performed the largest exome-sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared with randomly selected genes within the same patients and unaffected pediatric controls. IL acute myeloid leukemia (AML) patients had more overall variation than IL acute lymphocytic leukemia (ALL) patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins. PMID:24301523

Recombinant MCF247 Virus, Leukemogenesis, and Immunosuppression in AKR Mice

DTIC Science & Technology

1990-06-01

knowledge of thymic leukemia and lymphoma in the AKR mouse system. Early leukemia and lymphoma development in the AKR mouse strain is caused by the ...inevitable in all individuals in a high incidence strain (e.g. AKR), as the retrovirus is integrated into the germline and is transmitted by vertical...Only those strains in which virus could induce suppressor cells * developed leukemia (Kumar et al., 1976). The association of immunosuppression and

The immune receptor Trem1 cooperates with diminished DNA damage response to induce preleukemic stem cell expansion.

PubMed

Du, W; Amarachintha, S; Wilson, A; Pang, Q

2017-02-01

Fanconi anemia (FA) is an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Here we investigate the relationship between DNA damage response (DDR) and leukemogenesis using the Fanca knockout mouse model. We found that chronic exposure of the Fanca -/- hematopoietic stem cells to DNA crosslinking agent mitomycin C in vivo leads to diminished DDR, and the emergence/expansion of pre-leukemia stem cells (pre-LSCs). Surprisingly, although genetic correction of Fanca deficiency in the pre-LSCs restores DDR and reduces genomic instability, but fails to prevent pre-LSC expansion or delay leukemia development in irradiated recipients. Furthermore, we identified transcription program underlying dysregulated DDR and cell migration, myeloid proliferation, and immune response in the Fanca -/- pre-LSCs. Forced expression of the downregulated DNA repair genes, Rad51c or Trp53i13, in the Fanca -/- pre-LSCs partially rescues DDR but has no effect on leukemia, whereas shRNA knockdown of the upregulated immune receptor genes Trem1 or Pilrb improves leukemia-related survival, but not DDR or genomic instability. Furthermore, Trem1 cooperates with diminished DDR in vivo to promote Fanca -/- pre-LSC expansion and leukemia development. Our study implicates diminishing DDR as a root cause of FA leukemogenesis, which subsequently collaborates with other signaling pathways for leukemogenic transformation.

Requirement for CDK6 in MLL-rearranged acute myeloid leukemia

PubMed Central

Placke, Theresa; Faber, Katrin; Nonami, Atsushi; Putwain, Sarah L.; Salih, Helmut R.; Heidel, Florian H.; Krämer, Alwin; Root, David E.; Barbie, David A.; Krivtsov, Andrei V.; Armstrong, Scott A.; Hahn, William C.; Huntly, Brian J.; Sykes, Stephen M.; Milsom, Michael D.; Scholl, Claudia

2014-01-01

Chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) trigger aberrant gene expression in hematopoietic progenitors and give rise to an aggressive subtype of acute myeloid leukemia (AML). Insights into MLL fusion-mediated leukemogenesis have not yet translated into better therapies because MLL is difficult to target directly, and the identity of the genes downstream of MLL whose altered transcription mediates leukemic transformation are poorly annotated. We used a functional genetic approach to uncover that AML cells driven by MLL-AF9 are exceptionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the preferential growth inhibition induced by CDK6 depletion is mediated through enhanced myeloid differentiation. CDK6 essentiality is also evident in AML cells harboring alternate MLL fusions and a mouse model of MLL-AF9–driven leukemia and can be ascribed to transcriptional activation of CDK6 by mutant MLL. Importantly, the context-dependent effects of lowering CDK6 expression are closely phenocopied by a small-molecule CDK6 inhibitor currently in clinical development. These data identify CDK6 as critical effector of MLL fusions in leukemogenesis that might be targeted to overcome the differentiation block associated with MLL-rearranged AML, and underscore that cell-cycle regulators may have distinct, noncanonical, and nonredundant functions in different contexts. PMID:24764564

Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia.

PubMed

Nakamae, Ikuko; Kato, Jun-Ya; Yokoyama, Takashi; Ito, Hidenori; Yoneda-Kato, Noriko

2017-09-12

C/EBPα is a key transcription factor regulating myeloid differentiation and leukemogenesis. The Trib1-COP1 complex is an E3 ubiquitin ligase that targets C/EBPα for degradation, and its overexpression specifically induces acute myeloid leukemia (AML). Here we show that myeloid leukemia factor 1 (MLF1) stabilizes C/EBPα protein levels by inhibiting the ligase activity of the Trib1-COP1 complex. MLF1 directly interacts with COP1 in the nucleus and interferes with the formation of the Trib1-COP1 complex, thereby blocking its ability to polyubiquitinate C/EBPα for degradation. MLF1 overexpression suppressed the Trib1-induced growth advantage in a murine bone marrow (BM) culture and Trib1-induced AML development in BM-transplanted mouse models. MLF1 was expressed in hematopoietic stem cells and myeloid progenitors (common myeloid progenitors and granulocyte-macrophage progenitors) in normal hematopoiesis, which is consistent with the distribution of C/EBPα. An MLF1 deficiency conferred a more immature phenotype on Trib1-induced AML development. A higher expression ratio of Trib1 to MLF1 was a key determinant for AML development in mouse models, which was also confirmed in human patient samples with acute leukemia. These results indicate that MLF1 is a positive regulator that is critical for C/EBPα stability in the early phases of hematopoiesis and leukemogenesis.

Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia

PubMed Central

Nakamae, Ikuko; Kato, Jun-ya; Yokoyama, Takashi; Ito, Hidenori

2017-01-01

C/EBPα is a key transcription factor regulating myeloid differentiation and leukemogenesis. The Trib1-COP1 complex is an E3 ubiquitin ligase that targets C/EBPα for degradation, and its overexpression specifically induces acute myeloid leukemia (AML). Here we show that myeloid leukemia factor 1 (MLF1) stabilizes C/EBPα protein levels by inhibiting the ligase activity of the Trib1-COP1 complex. MLF1 directly interacts with COP1 in the nucleus and interferes with the formation of the Trib1-COP1 complex, thereby blocking its ability to polyubiquitinate C/EBPα for degradation. MLF1 overexpression suppressed the Trib1-induced growth advantage in a murine bone marrow (BM) culture and Trib1-induced AML development in BM-transplanted mouse models. MLF1 was expressed in hematopoietic stem cells and myeloid progenitors (common myeloid progenitors and granulocyte-macrophage progenitors) in normal hematopoiesis, which is consistent with the distribution of C/EBPα. An MLF1 deficiency conferred a more immature phenotype on Trib1-induced AML development. A higher expression ratio of Trib1 to MLF1 was a key determinant for AML development in mouse models, which was also confirmed in human patient samples with acute leukemia. These results indicate that MLF1 is a positive regulator that is critical for C/EBPα stability in the early phases of hematopoiesis and leukemogenesis. PMID:29296815

Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis

PubMed Central

Yuan, Hongfeng; Wang, Zhiqiang; Li, Ling; Zhang, Hao; Modi, Hardik; Horne, David

2012-01-01

The tyrosine kinase inhibitor imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but primary and acquired resistance of CML cells to the drug offset its efficacy. Molecular mechanisms for resistance of CML to tyrosine kinase inhibitors are not fully understood. In the present study, we show that BCR-ABL activates the expression of the mammalian stress response gene SIRT1 in hematopoietic progenitor cells and that this involves STAT5 signaling. SIRT1 activation promotes CML cell survival and proliferation associated with deacetylation of multiple SIRT1 substrates, including FOXO1, p53, and Ku70. Imatinib-mediated inhibition of BCR-ABL kinase activity partially reduces SIRT1 expression and SIRT1 inhibition further sensitizes CML cells to imatinib-induced apoptosis. Knockout of SIRT1 suppresses BCR-ABL transformation of mouse BM cells and the development of a CML-like myeloproliferative disease, and treatment of mice with the SIRT1 inhibitor tenovin-6 deters disease progression. The combination of SIRT1 gene knockout and imatinib treatment further extends the survival of CML mice. Our results suggest that SIRT1 is a novel survival pathway activated by BCR-ABL expression in hematopoietic progenitor cells, which promotes oncogenic transformation and leukemogenesis. Our findings suggest further exploration of SIRT1 as a therapeutic target for CML treatment to overcome resistance. PMID:22207735

Temporal Changes in FLT3 ITD Regulation of Stem Cell Self Renewal and Leukemogenesis

DTIC Science & Technology

2016-11-01

JAM is a 661   scholar of the Child Health Research Center for Excellence in Developmental 662   Biology at Washington University (K12-HD076224...SUPPLEMENTARY NOTES 14. ABSTRACT My goal is to understand how mechanisms that regulate normal hematopoietic development can also influence the mutation...pathways) in fetal, neonatal and adult progenitors. STAT5 was activated by FLT3-ITD at all stages of development , but MAPK was activated only in post

Temporal Changes in FLT3-ITD Regulation of Stem Cell Self-Renewal and Leukemogenesis

DTIC Science & Technology

2015-09-01

whether FLT3-ITD depletes HSCs, expands restricted progenitors and promotes a myeloproliferative neoplasm during the adult, but not fetal stage of...goals: Aim 1: To test whether FLT3-ITD depletes HSCs, expands restricted progenitors and promotes a myeloproliferative neoplasm during the adult, but...progenitor pool and myeloproliferative neoplasms (MPN) were also evident in 14 day old FLT3-ITD mice but not fetal mice (Fig. 1F and not shown). FLT3-ITD

Lmo2 expression defines tumor cell identity during T-cell leukemogenesis.

PubMed

García-Ramírez, Idoia; Bhatia, Sanil; Rodríguez-Hernández, Guillermo; González-Herrero, Inés; Walter, Carolin; González de Tena-Dávila, Sara; Parvin, Salma; Haas, Oskar; Woessmann, Wilhelm; Stanulla, Martin; Schrappe, Martin; Dugas, Martin; Natkunam, Yasodha; Orfao, Alberto; Domínguez, Verónica; Pintado, Belén; Blanco, Oscar; Alonso-López, Diego; De Las Rivas, Javier; Martín-Lorenzo, Alberto; Jiménez, Rafael; García Criado, Francisco Javier; García Cenador, María Begoña; Lossos, Izidore S; Vicente-Dueñas, Carolina; Borkhardt, Arndt; Hauer, Julia; Sánchez-García, Isidro

2018-06-07

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300.

PubMed

Mori, N; Morishita, M; Tsukazaki, T; Giam, C Z; Kumatori, A; Tanaka, Y; Yamamoto, N

2001-04-01

Human T-cell leukemia virus type I (HTLV-I) Tax is a potent transcriptional regulator that can activate or repress specific cellular genes and that has been proposed to contribute to leukemogenesis in adult T-cell leukemia. Previously, HTLV-I- infected T-cell clones were found to be resistant to growth inhibition by transforming growth factor (TGF)-beta. Here it is shown that Tax can perturb Smad-dependent TGF-beta signaling even though no direct interaction of Tax and Smad proteins could be detected. Importantly, a mutant Tax of CREB-binding protein (CBP)/p300 binding site, could not repress the Smad transactivation function, suggesting that the CBP/p300 binding domain of Tax is essential for the suppression of Smad function. Because both Tax and Smad are known to interact with CBP/p300 for the potentiation of their transcriptional activities, the effect of CBP/p300 on suppression of Smad-mediated transactivation by Tax was examined. Overexpression of CBP/p300 reversed Tax-mediated inhibition of Smad transactivation. Furthermore, Smad could repress Tax transcriptional activation, indicating reciprocal repression between Tax and Smad. These results suggest that Tax interferes with the recruitment of CBP/p300 into transcription initiation complexes on TGF-beta-responsive elements through its binding to CBP/p300. The novel function of Tax as a repressor of TGF-beta signaling may contribute to HTLV-I leukemogenesis. (Blood. 2001;97:2137-2144)

BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein

PubMed Central

Mackenzie, Ryan J.; Besson, Arnaud; Jeng, Sophia; Carey, Alyssa; LaTocha, Dorian H.; Fleischman, Angela G.; Duquesnes, Nicolas; Eide, Christopher A.; Vasudevan, Kavin B.; Loriaux, Marc M.; Firpo, Eduardo; Cortes, Jorge E.; McWeeney, Shannon; O’Hare, Thomas; Roberts, James M.; Druker, Brian J.; Deininger, Michael W.

2014-01-01

Recent studies have revealed that p27, a nuclear cyclin-dependent kinase (Cdk) inhibitor and tumor suppressor, can acquire oncogenic activities upon mislocalization to the cytoplasm. To understand how these antagonistic activities influence oncogenesis, we dissected the nuclear and cytoplasmic functions of p27 in chronic myeloid leukemia (CML), a well-characterized malignancy caused by the BCR-ABL1 tyrosine kinase. p27 is predominantly cytoplasmic in CML and nuclear in normal cells. BCR-ABL1 regulates nuclear and cytoplasmic p27 abundance by kinase-dependent and -independent mechanisms, respectively. p27 knockdown in CML cell lines with predominantly cytoplasmic p27 induces apoptosis, consistent with a leukemogenic role of cytoplasmic p27. Accordingly, a p27 mutant (p27CK−) devoid of Cdk inhibitory nuclear functions enhances leukemogenesis in a murine CML model compared with complete absence of p27. In contrast, p27 mutations that enhance its stability (p27T187A) or nuclear retention (p27S10A) attenuate leukemogenesis over wild-type p27, validating the tumor-suppressor function of nuclear p27 in CML. We conclude that BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. These findings suggest that cytoplasmic mislocalization of p27 despite BCR-ABL1 inhibition by tyrosine kinase inhibitors may contribute to drug resistance, and effective therapeutic strategies to stabilize nuclear p27 must also prevent cytoplasmic mislocalization. PMID:25293778

34 CFR 350.5 - What definitions apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... classified on a continuum from basic to applied: (1) Basic research is research in which the investigator is... immediate application or utility. (2) Applied research is research in which the investigator is primarily... rehabilitation problem or need. Applied research builds on selected findings from basic research. (Authority: Sec...

The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

PubMed Central

Janczar, Szymon; Janczar, Karolina; Pastorczak, Agata; Harb, Hani; Paige, Adam J. W.; Zalewska-Szewczyk, Beata; Danilewicz, Marian; Mlynarski, Wojciech

2017-01-01

While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis. PMID:28054944

Diet and risk of leukemia in the Iowa Women's Health Study.

PubMed

Ross, Julie A; Kasum, Christine M; Davies, Stella M; Jacobs, David R; Folsom, Aaron R; Potter, John D

2002-08-01

Nearly 30,000 individuals ages over 21 years are diagnosed with leukemia each year in the United States. Other than benzene, radiation, and chemotherapy, which account for a small proportion of cases, there are few identified risk factors for adult leukemia. Although recent data from animal studies indicate a potentially protective role for dietary restriction in leukemogenesis, few data exist on dietary relationships in adult leukemia. Food frequency data collected at baseline (1986) were analyzed from the prospective Iowa Women's Health Study to begin to address the role of diet in adult leukemia. Data from 35,221 women ages 55-69 years were analyzed. A total of 138 women developed leukemia during the 14-year follow-up period of 1986 to 1999. With the exception of an inverse association (P trend = 0.08) with increasing consumption of all vegetables (relative risk, 0.56 and 95% confidence interval, 0.36-0.88; relative risk, 0.69 and 95% confidence interval, 0.44-1.07 for medium and high consumption, respectively), there was little evidence of an important role for other dietary factors in leukemogenesis. Analyses that excluded cases diagnosed in the first 2 years from baseline did not notably alter the results. Leukemia subgroups, including acute myeloid leukemia and chronic lymphoblastic leukemia, were also analyzed, but no statistically significant associations with dietary factors were revealed. This study provides evidence that increased vegetable consumption may decrease the risk of adult leukemia. However, given that our study focused on older women from a defined geographical area, analyses of prospective studies in other populations are needed to confirm or refute these results.

Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance.

PubMed

Vukovic, Milica; Guitart, Amelie V; Sepulveda, Catarina; Villacreces, Arnaud; O'Duibhir, Eoghan; Panagopoulou, Theano I; Ivens, Alasdair; Menendez-Gonzalez, Juan; Iglesias, Juan Manuel; Allen, Lewis; Glykofrydis, Fokion; Subramani, Chithra; Armesilla-Diaz, Alejandro; Post, Annemarie E M; Schaak, Katrin; Gezer, Deniz; So, Chi Wai Eric; Holyoake, Tessa L; Wood, Andrew; O'Carroll, Dónal; Ratcliffe, Peter J; Kranc, Kamil R

2015-12-14

Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance. © 2015 Vukovic et al.

Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance

PubMed Central

Vukovic, Milica; Guitart, Amelie V.; Sepulveda, Catarina; Villacreces, Arnaud; O'Duibhir, Eoghan; Panagopoulou, Theano I.; Ivens, Alasdair; Menendez-Gonzalez, Juan; Iglesias, Juan Manuel; Allen, Lewis; Glykofrydis, Fokion; Subramani, Chithra; Armesilla-Diaz, Alejandro; Post, Annemarie E.M.; Schaak, Katrin; Gezer, Deniz; So, Chi Wai Eric; Holyoake, Tessa L.; Wood, Andrew; O'Carroll, Dónal; Ratcliffe, Peter J.

2015-01-01

Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance. PMID:26642852

Histone acetyltransferase activity of MOF is required for MLL-AF9 leukemogenesis

PubMed Central

Valerio, Daria G.; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E.; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J.; Huang, Chun-Hao; Lujambio, Amaia; Zheng, George; Zuber, Johannes; Pandita, Tej K.; Lowe, Scott W.; Armstrong, Scott A.

2017-01-01

Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore Mof inactivation suppressed leukemia development in a NUP98-HOXA9 driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. PMID:28202522

SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasia

PubMed Central

Gu, Shengqing; Sayad, Azin; Chan, Gordon; Yang, Wentian; Lu, Zhibin; Virtanen, Carl; Van Etten, Richard A.; Neel, Benjamin G.

2017-01-01

BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+ B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia. Ptpn11 deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+ B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+ pre-B cells, but is only required for the proliferation of BCR-ABL1+ cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+ pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+ and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, represses MXD3/4 to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells. PMID:28804122

Targeting of the BLT2 in chronic myeloid leukemia inhibits leukemia stem/progenitor cell function

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

Xiao, Meifang; Ai, Hongmei; Li, Tao

Imatinib, a tyrosine kinase inhibitor (TKI) has significantly improved clinical outcome for chronic myeloid leukemia (CML) patients. However, patients develop resistance when the disease progresses to the blast phase (BP) and the mechanisms are not well understood. Here we show that BCR-ABL activates BLT2 in hematopoietic stem/progenitor cells to promote leukemogenesis and this involves the p53 signaling pathway. Compared to normal bone marrow (NBM), the mRNA and protein levels of BLT2 are significantly increased in BP-CML CD34{sup +} stem/progenitor cells. This is correlated with increasing BCR-ABL expression. In contrast, knockdown of BCR-ABL or inhibition of its tyrosine kinase activity decreasesmore » Blt2 protein level. BLT2 inhibition induces apoptosis, inhibits proliferation, colony formation and self-renewal capacity of CD34{sup +} cells from TKI-resistant BP-CML patients. Importantly, the inhibitory effects of BCR-ABL TKI on CML stem/progenitor cells are further enhanced upon combination with BLT2 inhibition. We further show that BLT2 activation selectively suppresses p53 but not Wnt or BMP-mediated luciferase activity and transcription. Our results demonstrate that BLT2 is a novel pathway activated by BCR-ABL and critically involved in the resistance of BP-CML CD34{sup +} stem/progenitors to TKIs treatment. Our findings suggest that BLT2 and p53 can serve as therapeutic targets for CML treatment. - Highlights: • BCR-ABL regulates BLT2 expression to promote leukemogenesis. • BLT2 is essential to maintain CML cell function. • Activation of BLT2 suppresses p53 signaling pathway in CML cells. • Inhibition of BLT2 and BCR-ABL synergize in eliminating CML CD34{sup +} stem/progenitors.« less

Elevated MLF1 expression correlates with malignant progression from myelodysplastic syndrome.

PubMed

Matsumoto, N; Yoneda-Kato, N; Iguchi, T; Kishimoto, Y; Kyo, T; Sawada, H; Tatsumi, E; Fukuhara, S

2000-10-01

MLF1 is a novel protein identified as the NPM-MLF1 chimeric protein produced by a t(3;5)(q25.1;q34) chromosomal translocation, which is associated with myelodysplastic syndrome (MDS), often prior to acute myeloid leukemia (AML), except for M3. The clinical features of t(3;5)-positive myeloid disorders suggest that this chimeric protein is involved in dysregulation of progenitor cells with the capability to differentiate into multiple lineages. So far, involvement of wild-type MLF1 in hematopoiesis or in leukemogenesis has not been fully investigated. In the present study, 65 patients with AML and 44 patients with MDS were tested for the expression of MLF1 using the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. A significantly higher level of MLF1 expression (ratio of MLF1/beta-actin mRNA >0.4) was readily detected in seven of 65 patients with de novo AML, three of 12 with post-MDS AML and seven of 44 with MDS, but not in any patients with ALL (n = 18). According to the FAB classification, high levels of MLF1 were found in patients with relatively immature subtypes of AML (M1, M2, M6 and M7) and high risk MDS (RAEB and RAEB-T). These findings indicate that the pattern of MLF1 expression is identical to the clinical morphology appearing in the t(3;5)-positive myeloid disorders and is correlated to the MDS-associated AML and transformation phase of MDS in t(3;5)-negative myeloid disorders. A CD34+ population of normal bone marrow cells preferentially expressed MLF1 with obviously decreasing levels of expression during maturation. Therefore, MLF1 normally functions in multi-potent progenitor cells and its dysregulation may take part in leukemogenesis from MDS.

Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

PubMed

Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

2017-04-01

Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9 -driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof -deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9 -driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL -rearranged leukemias. Cancer Res; 77(7); 1753-62. ©2017 AACR . ©2017 American Association for Cancer Research.

Translational research in behavior analysis: historical traditions and imperative for the future.

PubMed

Mace, F Charles; Critchfield, Thomas S

2010-05-01

"Pure basic" science can become detached from the natural world that it is supposed to explain. "Pure applied" work can become detached from fundamental processes that shape the world it is supposed to improve. Neither demands the intellectual support of a broad scholarly community or the material support of society. Translational research can do better by seeking innovation in theory or practice through the synthesis of basic and applied questions, literatures, and methods. Although translational thinking has always occurred in behavior analysis, progress often has been constrained by a functional separation of basic and applied communities. A review of translational traditions in behavior analysis suggests that innovation is most likely when individuals with basic and applied expertise collaborate. Such innovation may have to accelerate for behavior analysis to be taken seriously as a general-purpose science of behavior. We discuss the need for better coordination between the basic and applied sectors, and argue that such coordination compromises neither while benefiting both.

Speaking of food: connecting basic and applied plant science.

PubMed

Gross, Briana L; Kellogg, Elizabeth A; Miller, Allison J

2014-10-01

The Food and Agriculture Organization (FAO) predicts that food production must rise 70% over the next 40 years to meet the demands of a growing population that is expected to reach nine billion by the year 2050. Many facets of basic plant science promoted by the Botanical Society of America are important for agriculture; however, more explicit connections are needed to bridge the gap between basic and applied plant research. This special issue, Speaking of Food: Connecting Basic and Applied Plant Science, was conceived to showcase productive overlaps of basic and applied research to address the challenges posed by feeding billions of people and to stimulate more research, fresh connections, and new paradigms. Contributions to this special issue thus illustrate some interactive areas of study in plant science-historical and modern plant-human interaction, crop and weed origins and evolution, and the effects of natural and artificial selection on crops and their wild relatives. These papers provide examples of how research integrating the basic and applied aspects of plant science benefits the pursuit of knowledge and the translation of that knowledge into actions toward sustainable production of crops and conservation of diversity in a changing climate. © 2014 Botanical Society of America, Inc.

A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus Oncoprotein Tax-1-Driven Transformation In Vivo

PubMed Central

Shirinian, Margret; Kambris, Zakaria; Hamadeh, Lama; Grabbe, Caroline; Journo, Chloé; Mahieux, Renaud

2015-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. HTLV-2 is genetically related to HTLV-1 but does not cause any malignant disease. HTLV-1 Tax transactivator (Tax-1) contributes to leukemogenesis via NF-κB. We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. We demonstrate that Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte proliferation and that the eye phenotype is dependent on Kenny (IKKγ/NEMO), thus validating this new in vivo model. PMID:25995252

Down syndrome, RASopathies, and other rare syndromes.

PubMed

Kratz, Christian P; Izraeli, Shai

2017-04-01

In this article we discuss the occurrence of myeloid neoplasms in patients with a range of syndromes that are due to germline defects of the RAS signaling pathway and in patients with trisomy 21. Both RAS mutations and trisomy 21 are common somatic events contributing to leukemogenis. Thus, the increased leukemia risk observed in children affected by these conditions is biologically highly plausible. Children with myeloid neoplasms in the context of these syndromes require different treatments than children with sporadic myeloid neoplasms and provide an opportunity to study the role of trisomy 21 and RAS signaling during leukemogenesis and development. Copyright © 2017 Elsevier Inc. All rights reserved.

The Relationship between Basic and Applied Research in Universities

ERIC Educational Resources Information Center

Bentley, Peter James; Gulbrandsen, Magnus; Kyvik, Svein

2015-01-01

What is the central research activity in modern universities? This paper uses a comprehensive survey among individuals from 15 countries to map differences in orientation towards basic/fundamental research, applied/practical research and a combination of the two. Despite some claims in the literature that basic research is no longer a…

Basic research needed for stimulating the development of behavioral technologies

PubMed Central

Mace, F. Charles

1994-01-01

The costs of disconnection between the basic and applied sectors of behavior analysis are reviewed, and some solutions to these problems are proposed. Central to these solutions are collaborations between basic and applied behavioral scientists in programmatic research that addresses the behavioral basis and solution of human behavior problems. This kind of collaboration parallels the deliberate interactions between basic and applied researchers that have proven to be so profitable in other scientific fields, such as medicine. Basic research questions of particular relevance to the development of behavioral technologies are posed in the following areas: response allocation, resistance to change, countercontrol, formation and differentiation/discrimination of stimulus and response classes, analysis of low-rate behavior, and rule-governed behavior. Three interrelated strategies to build connections between the basic and applied analysis of behavior are identified: (a) the development of nonhuman animal models of human behavior problems using operations that parallel plausible human circumstances, (b) replication of the modeled relations with human subjects in the operant laboratory, and (c) tests of the generality of the model with actual human problems in natural settings. PMID:16812734

Money Management and the Consumer, Basic Economic Skills: "Baffled, Bothered, Bewildered".

ERIC Educational Resources Information Center

Florida State Dept. of Education, Tallahassee. Div. of Elementary and Secondary Education.

This document, one in a series of six Project SCAT (Skills for Consumers Applied Today) units for senior high school students, provides an overview of basic economic skills and consumer practices. Project SCAT is designed to help students develop basic skills, solve problems, and apply consumer knowledge necessary for making wise choices in the…

Can an Understanding of Basic Research Facilitate the Effectiveness of Practitioners? Reflections and Personal Perspectives

ERIC Educational Resources Information Center

Sidman, Murray

2011-01-01

I have written before about the importance of applied behavior analysis to basic researchers. That relationship is, however, reciprocal; it is also critical for practitioners to understand and even to participate in basic research. Although applied problems are rarely the same as those investigated in the laboratory, practitioners who understand…

32 CFR 34.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Basic, applied, and advanced research activities. Basic research is defined as efforts directed toward increasing knowledge or understanding in science and engineering. Applied research is defined as efforts that...). TIAs are covered by part 37 of the DoDGARs (32 CFR part 37). Portions of this part may apply to a TIA...

48 CFR 27.404-4 - Contractor's release, publication, and use of data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... reporting on the results of unclassified basic or applied research, except as provided in applicable U.S... applied research. Agencies may also preclude a contractor from asserting copyright in any computer... purpose for which the software is acquired. (b) Except for the results of basic or applied research under...

A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus Oncoprotein Tax-1-Driven Transformation In Vivo.

PubMed

Shirinian, Margret; Kambris, Zakaria; Hamadeh, Lama; Grabbe, Caroline; Journo, Chloé; Mahieux, Renaud; Bazarbachi, Ali

2015-08-01

Human T-cell lymphotropic virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. HTLV-2 is genetically related to HTLV-1 but does not cause any malignant disease. HTLV-1 Tax transactivator (Tax-1) contributes to leukemogenesis via NF-κB. We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. We demonstrate that Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte proliferation and that the eye phenotype is dependent on Kenny (IKKγ/NEMO), thus validating this new in vivo model. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

76 FR 38666 - Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... actively involved in both basic and applied research in coastal waters of the northern Gulf of Mexico. The... between the Center for Food Safety and Applied Nutrition (CFSAN) and the Marine Environmental Sciences Consortium/Dauphin Island Sea Lab (DISL). The goal of the DISL is marine science education, basic and applied...

Basic and Applied Research on Education and Social Inequality: Proceedings of the New York Education Policy Seminar (6th, Albany, New York, November 1988).

ERIC Educational Resources Information Center

Alexander, Karl L.; And Others

A seminar paper concerning the relationship between applied and basic research in the study of educational and social inequality, and two commentaries are presented. The paper--"In Defense of Ivory-Towerism: Confessions of an Unreconstructed Basic Researcher," by Karl L. Alexander, the seminar's main speaker, presents the point of view of a…

Novel adapter proteins that link the human GM-CSF receptor to the phosphatidylino-sitol 3-kinase and Shc/Grb2/ras signaling pathways.

PubMed

Jücker, M; Feldman, R A

1996-01-01

We have used a human GM-CSF-dependent hematopoietic cell line that responds to physiological concentrations of hGM-CSF to analyze a set of signaling events that occur in normal myelopoiesis and whose deregulation may lead to leukemogenesis. Stimulation of these cells with hGM-CSF induced the assembly of multimeric complexes that contained known and novel phosphotyrosyl proteins. One of the new proteins was a major phosphotyrosyl substrate of 76-85 kDa (p80) that was directly associated with the p85 subunit of phosphatidylinositol (PI) 3-kinase through the SH2 domains of p85. p80 also associated with the beta subunit of the activated hGM-CSF receptor, and assembly of this complex correlated with activation of PI 3-kinase. A second phosphotyrosyl protein we identified, p140, associated with the Shc and Grb2 adapter proteins by direct binding to a novel phosphotyrosine-interacting domain located at the N-terminus of Shc. and to the SH3 domains of Grb2, respectively. The Shc/p140/Grb2 complex was found to be constitutively activated in acute myeloid leukemia cells, indicating that activation of this pathway may be a necessary step in the development of some leukemias. The p80/p85/PI 3-kinase and the Shc/Grb2/p140 complexes were tightly associated with Src family kinases, which were prime candidates for phosphorylation of Shc, p80, p140 and other phosphotyrosyl substrates present in these complexes. Our studies suggest that p80 and p140 may link the hGM-CSF receptor to the PI 3-kinase and Shc/Grb2/ras signaling pathways, respectively, and that abnormal activation of hGM-CSF-dependent targets may play a role in leukemogenesis.

EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia

PubMed Central

Charmsaz, Sara; Beckett, Kirrilee; Smith, Fiona M.; Bruedigam, Claudia; Moore, Andrew S.; Al-Ejeh, Fares; Lane, Steven W.; Boyd, Andrew W.

2015-01-01

Members of the Eph family of receptor tyrosine kinases and their membrane bound ephrin ligands have been shown to play critical roles in many developmental processes and more recently have been implicated in both normal and pathological processes in post-embryonic tissues. In particular, expression studies of Eph receptors and limited functional studies have demonstrated a role for the Eph/ephrin system in hematopoiesis and leukemogenesis. In particular, EphA2 was reported on hematopoietic stem cells and stromal cells. There are also reports of EphA2 expression in many different types of malignancies including leukemia, however there is a lack of knowledge in understanding the role of EphA2 in hematopoiesis and leukemogenesis. We explored the role of EphA2 in hematopoiesis by analyzing wild type and EphA2 knockout mice. Mature, differentiated cells, progenitors and hematopoietic stem cells derived from knockout and control mice were analyzed and no significant abnormality was detected. These studies showed that EphA2 does not have an obligatory role in normal hematopoiesis. Comparative studies using EphA2-negative MLL-AF9 leukemias derived from EphA2-knockout animals showed that there was no detectable functional role for EphA2 in the initiation or progression of the leukemic process. However, expression of EphA2 in leukemias initiated by MLL-AF9 suggested that this protein might be a possible therapy target in this type of leukemia. We showed that treatment with EphA2 monoclonal antibody IF7 alone had no effect on tumorigenicity and latency of the MLL-AF9 leukemias, while targeting of EphA2 using EphA2 monoclonal antibody with a radioactive payload significantly impaired the leukemic process. Altogether, these results identify EphA2 as a potential radio-therapeutic target in leukemias with MLL translocation. PMID:26083390

EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia.

PubMed

Charmsaz, Sara; Beckett, Kirrilee; Smith, Fiona M; Bruedigam, Claudia; Moore, Andrew S; Al-Ejeh, Fares; Lane, Steven W; Boyd, Andrew W

2015-01-01

Members of the Eph family of receptor tyrosine kinases and their membrane bound ephrin ligands have been shown to play critical roles in many developmental processes and more recently have been implicated in both normal and pathological processes in post-embryonic tissues. In particular, expression studies of Eph receptors and limited functional studies have demonstrated a role for the Eph/ephrin system in hematopoiesis and leukemogenesis. In particular, EphA2 was reported on hematopoietic stem cells and stromal cells. There are also reports of EphA2 expression in many different types of malignancies including leukemia, however there is a lack of knowledge in understanding the role of EphA2 in hematopoiesis and leukemogenesis. We explored the role of EphA2 in hematopoiesis by analyzing wild type and EphA2 knockout mice. Mature, differentiated cells, progenitors and hematopoietic stem cells derived from knockout and control mice were analyzed and no significant abnormality was detected. These studies showed that EphA2 does not have an obligatory role in normal hematopoiesis. Comparative studies using EphA2-negative MLL-AF9 leukemias derived from EphA2-knockout animals showed that there was no detectable functional role for EphA2 in the initiation or progression of the leukemic process. However, expression of EphA2 in leukemias initiated by MLL-AF9 suggested that this protein might be a possible therapy target in this type of leukemia. We showed that treatment with EphA2 monoclonal antibody IF7 alone had no effect on tumorigenicity and latency of the MLL-AF9 leukemias, while targeting of EphA2 using EphA2 monoclonal antibody with a radioactive payload significantly impaired the leukemic process. Altogether, these results identify EphA2 as a potential radio-therapeutic target in leukemias with MLL translocation.

A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation.

PubMed

Yagita, M; Huang, C L; Umehara, H; Matsuo, Y; Tabata, R; Miyake, M; Konaka, Y; Takatsuki, K

2000-05-01

We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.

Cell cycle regulatory gene abnormalities are important determinants of leukemogenesis and disease biology in adult acute lymphoblastic leukemia.

PubMed

Stock, W; Tsai, T; Golden, C; Rankin, C; Sher, D; Slovak, M L; Pallavicini, M G; Radich, J P; Boldt, D H

2000-04-01

To test the hypothesis that cell cycle regulatory gene abnormalities are determinants of clinical outcome in adult acute lymphoblastic leukemia (ALL), we screened lymphoblasts from patients on a Southwest Oncology Group protocol for abnormalities of the genes, retinoblastoma (Rb), p53, p15(INK4B), and p16(INK4A). Aberrant expression occurred in 33 (85%) patients in the following frequencies: Rb, 51%; p16(INK4A), 41%; p53, 26%. Thirteen patients (33%) had abnormalities in 2 or more genes. Outcomes were compared in patients with 0 to 1 abnormality versus patients with multiple abnormalities. The 2 groups did not differ in a large number of clinical and laboratory characteristics. The CR rates for patients with 0 to 1 and multiple abnormalities were similar (69% and 54%, respectively). Patients with 0 to 1 abnormality had a median survival time of 25 months (n = 26; 95% CI, 13-46 months) versus 8 months (n = 13; 95% CI, 4-12 months) for those with multiple abnormalities (P <.01). Stem cells (CD34+lin-) were isolated from adult ALL bone marrows and tested for p16(INK4A) expression by immunocytochemistry. In 3 of 5 patients lymphoblasts and sorted stem cells lacked p16(INK4A) expression. In 2 other patients only 50% of sorted stem cells expressed p16(INK4A). By contrast, p16 expression was present in the CD34+ lin- compartment in 95% (median) of 9 patients whose lymphoblasts expressed p16(INK4A). Therefore, cell cycle regulatory gene abnormalities are frequently present in adult ALL lymphoblasts, and they may be important determinants of disease outcome. The presence of these abnormalities in the stem compartment suggests that they contribute to leukemogenesis. Eradication of the stem cell subset harboring these abnormalities may be important to achieve cure.

Challenges for Engineering Design, Construction, and Maintenance of Infrastructure in Afghanistan

DTIC Science & Technology

2010-11-01

applied engineering expertise that collectively can solve challenging infra- structure problems. USACE-ERDC’s researchers and engineers are field...Development Center (ERDC) possesses a unique combination of basic research and applied engineering expertise that collectively can solve challenging...restoration, and other projects. The USACE Engineer Research and Development Center (ERDC) possesses a unique combination of basic research and applied

10 CFR 605.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... definitions are provided for purposes of this part— Basic and applied research means basic and applied research and that part of development not related to the development of specific systems or products. The... ENERGY (CONTINUED) ASSISTANCE REGULATIONS THE OFFICE OF ENERGY RESEARCH FINANCIAL ASSISTANCE PROGRAM...

The Impact of "Coat Protein-Mediated Virus Resistance" in Applied Plant Pathology and Basic Research.

PubMed

Lindbo, John A; Falk, Bryce W

2017-06-01

Worldwide, plant viruses cause serious reductions in marketable crop yield and in some cases even plant death. In most cases, the most effective way to control virus diseases is through genetically controlled resistance. However, developing virus-resistant (VR) crops through traditional breeding can take many years, and in some cases is not even possible. Because of this, the demonstration of the first VR transgenic plants in 1985 generated much attention. This seminal report served as an inflection point for research in both basic and applied plant pathology, the results of which have dramatically changed both basic research and in a few cases, commercial crop production. The typical review article on this topic has focused on only basic or only applied research results stemming from this seminal discovery. This can make it difficult for the reader to appreciate the full impact of research on transgenic virus resistance, and the contributions from fundamental research that led to translational applications of this technology. In this review, we take a global view of this topic highlighting the significant changes to both basic and applied plant pathology research and commercial food production that have accumulated in the last 30 plus years. We present these milestones in the historical context of some of the scientific, economic, and environmental drivers for developing specific VR crops. The intent of this review is to provide a single document that adequately records the significant accomplishments of researchers in both basic and applied plant pathology research on this topic and how they relate to each other. We hope this review therefore serves as both an instructional tool for students new to the topic, as well as a source of conversation and discussion for how the technology of engineered virus resistance could be applied in the future.

Operations Research Applied to Libraries.

ERIC Educational Resources Information Center

Nussbaum, Harvey

This report discusses the seven basic types of problems found in business and industry as they apply to library institutions. These seven basic types are: (1) inventory problems, (2) allocation problems, (3) queueing problems, (4) sequencing problems, (5) routing problems, (6) replacement problems and (7) search problems. (MF)

Thinking science with thinking machines: The multiple realities of basic and applied knowledge in a research border zone.

PubMed

Hoffman, Steve G

2015-04-01

Some scholars dismiss the distinction between basic and applied science as passé, yet substantive assumptions about this boundary remain obdurate in research policy, popular rhetoric, the sociology and philosophy of science, and, indeed, at the level of bench practice. In this article, I draw on a multiple ontology framework to provide a more stable affirmation of a constructivist position in science and technology studies that cannot be reduced to a matter of competing perspectives on a single reality. The analysis is grounded in ethnographic research in the border zone of Artificial Intelligence science. I translate in-situ moments in which members of neighboring but differently situated labs engage in three distinct repertoires that render the reality of basic and applied science: partitioning, flipping, and collapsing. While the essences of scientific objects are nowhere to be found, the boundary between basic and applied is neither illusion nor mere propaganda. Instead, distinctions among scientific knowledge are made real as a matter of course.

Hematopoietic stem cell engineering at a crossroads.

PubMed

Rivière, Isabelle; Dunbar, Cynthia E; Sadelain, Michel

2012-02-02

The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.

Student Teachers' Attitudes about Basic Physics Laboratory

ERIC Educational Resources Information Center

Yesilyurt, Mustafa

2004-01-01

In this study an attitude questionnaire was developed and applied to identify student teachers' interests and attitudes for basic physics laboratory. In physics laboratory practices run by a higher education institution a new attitude questionnaire was developed and applied twice in two terms by researchers to increase student teachers' success…

Technology Literacy: A Key to the New Basic Skills.

ERIC Educational Resources Information Center

Brown, Richard

The United States needs a vocational educational system that delivers, in an applied technological setting, the new basic skills that industry needs, as well as a general education system that provides creative instruction in applied math, physics, and science. To be effective, technological training should encompass, along with machine-specific…

Geometric Error Analysis in Applied Calculus Problem Solving

ERIC Educational Resources Information Center

Usman, Ahmed Ibrahim

2017-01-01

The paper investigates geometric errors students made as they tried to use their basic geometric knowledge in the solution of the Applied Calculus Optimization Problem (ACOP). Inaccuracies related to the drawing of geometric diagrams (visualization skills) and those associated with the application of basic differentiation concepts into ACOP…

10 CFR 605.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Definitions. 605.3 Section 605.3 Energy DEPARTMENT OF... § 605.3 Definitions. In addition to the definitions provided in 10 CFR part 600, the following definitions are provided for purposes of this part— Basic and applied research means basic and applied...

A roadmap for bridging basic and applied research in forensic entomology.

PubMed

Tomberlin, J K; Mohr, R; Benbow, M E; Tarone, A M; VanLaerhoven, S

2011-01-01

The National Research Council issued a report in 2009 that heavily criticized the forensic sciences. The report made several recommendations that if addressed would allow the forensic sciences to develop a stronger scientific foundation. We suggest a roadmap for decomposition ecology and forensic entomology hinging on a framework built on basic research concepts in ecology, evolution, and genetics. Unifying both basic and applied research fields under a common umbrella of terminology and structure would facilitate communication in the field and the production of scientific results. It would also help to identify novel research areas leading to a better understanding of principal underpinnings governing ecosystem structure, function, and evolution while increasing the accuracy of and ability to interpret entomological evidence collected from crime scenes. By following the proposed roadmap, a bridge can be built between basic and applied decomposition ecology research, culminating in science that could withstand the rigors of emerging legal and cultural expectations.

Genital Measures: Comments on Their Role in Understanding Human Sexuality

ERIC Educational Resources Information Center

Geer, James H.

1976-01-01

This paper discusses the use of genital measures in the study of both applied and basic work in human sexuality. Some of the advantages of psychophysiological measures are considered along with cautions concerning unwarranted assumptions. Some of the advances that are possible in both applied and basic work are examined. (Author)

34 CFR 460.4 - What definitions apply to the adult education programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... adult education programs: Act means the Adult Education Act (20 U.S.C. 1201 et seq.). Adult basic... basic education includes grades 0 through 8.9. Adult secondary education means instruction designed for... 34 Education 3 2013-07-01 2013-07-01 false What definitions apply to the adult education programs...

34 CFR 460.4 - What definitions apply to the adult education programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... adult education programs: Act means the Adult Education Act (20 U.S.C. 1201 et seq.). Adult basic... basic education includes grades 0 through 8.9. Adult secondary education means instruction designed for... 34 Education 3 2014-07-01 2014-07-01 false What definitions apply to the adult education programs...

34 CFR 460.4 - What definitions apply to the adult education programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... adult education programs: Act means the Adult Education Act (20 U.S.C. 1201 et seq.). Adult basic... basic education includes grades 0 through 8.9. Adult secondary education means instruction designed for... 34 Education 3 2012-07-01 2012-07-01 false What definitions apply to the adult education programs...

R and D Evaluation Workshop report, U.S. Department of Energy, Office of Energy Research, September 7--8, 1995

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

Jordan, G.

1995-10-30

The objective of the workshop was to promote discussions between experts and research managers on developing approaches for assessing the impact of DOE`s basic energy research upon the energy mission, applied research, technology transfer, the economy, and society. The purpose of this impact assessment is to demonstrate results and improve ER research programs in this era when basic research is expected to meet changing national economic and social goals. The questions addressed were: (1) By what criteria and metrics does Energy Research measure performance and evaluate its impact on the DOE mission and society while maintaining an environment that fostersmore » basic research? (2) What combination of evaluation methods best applies to assessing the performance and impact of OBES basic research? The focus will be upon the following methods: Case studies, User surveys, Citation analysis, TRACES approach, Return on DOE investment (ROI)/Econometrics, and Expert panels. (3) What combination of methods and specific rules of thumb can be applied to capture impacts along the spectrum from basic research to products and societal impacts?« less

The role of universities in energy and environmental R & D: An extended outline

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

Drucker, H.

1995-12-31

Issues related to university research and development roles in energy and environmental areas are very briefly outlined in the paper. Fundamental issues discussed include basic versus applied science, and applied science versus technology development. Some specific issues appropriate for university research are identified, such as desulfurizing coal and managing mixed wastes in groundwater. The Plant Biotechnology consortium is described as a model that builds on university strengths in basic and applied technology.

Hematopoietic stem cell engineering at a crossroads

PubMed Central

Rivière, Isabelle; Dunbar, Cynthia E.

2012-01-01

The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead. PMID:22096239

Teaching Basic Science Content via Real-World Applications: A College-Level Summer Course in Veterinary Anatomy and Physiology

ERIC Educational Resources Information Center

Maza, Paul; Miller, Allison; Carson, Brian; Hermanson, John

2018-01-01

Learning and retaining science content may be increased by applying the basic science material to real-world situations. Discussing cases with students during lectures and having them participate in laboratory exercises where they apply the science content to practical situations increases students' interest and enthusiasm. A summer course in…

Psychological Literacy in Applied Psychology Disciplines: Back to, or Beyond, the Basics?

ERIC Educational Resources Information Center

Tomcho, Thomas J.; Foels, Rob

2017-01-01

Undergraduate psychology majors need a broad base of knowledge in order to be viewed as competent graduates. In addition to acquiring basic knowledge, the American Psychological Association (APA) has guidelines for applied knowledge as well. In order to ensure a broad base of knowledge, teachers therefore need to know what the important…

Applied vs Basic Research: On Maintaining Your Balance with a Foot in Each Camp.

ERIC Educational Resources Information Center

Martin, David W.

The paper discusses a number of issues concerning the practical usefulness of cognitive psychology research, and presents a case study of pilot training methods to illustrate a model of research processes that produces outcomes which contribute to both basic and applied research goals. Research studies are described as varying in the degree to…

21 CFR 1303.12 - Procurement quotas.

Code of Federal Regulations, 2011 CFR

2011-04-01

... purposes of manufacturing, shall apply on DEA Form 250 for a procurement quota for such basic class. A... specified unit of the second basic class. DEA Form 250 shall be filed on or before April 1 of the year preceding the calendar year for which the procurement quota is being applied. Copies of DEA Form 250 may be...

BRIDGES: Evolution of basic and applied linkages in benthic science

USGS Publications Warehouse

Aumen, Nicholas G.; Gurtz, Martin E.; Barbour, Michael T.; Moerke, Ashley

2010-01-01

Growing awareness of environmental degradation resulted in stricter environmental regulations and laws for aquatic ecosystems. These regulations were followed by an increase in applied research and monitoring beginning in the early 1970s. The number of applied scientists who were members of the North American Benthological Society grew at a commensurate rate. The editors of J-NABS recognized that, despite these increases, submitted manuscripts mostly addressed basic science. In response, the BRIDGES section of J-NABS was created in 1994 to provide a forum for linking basic ecological principles to applied science problems and issues. We examined the emergence of applied science topics in J-NABS and its predecessor, Freshwater Invertebrate Biology, from their beginning in 1982 to 2009. We classified papers among 11 categories that included a basic/applied science linkage. In the 1980s, applied papers were predominantly on effects of eutrophication/pollution and landuse changes. When BRIDGES was established in 1994, papers were solicited by editors and BRIDGES sections usually included >1 paper on a common theme to express complementary or alternate viewpoints. Forty-two papers appeared in BRIDGES between 1994 and 2009, but the number per issue declined after 2001. The total number of applied science papers in J-NABS has increased since ∼1994. Citation analysis of BRIDGES papers illustrates how information is being cited, but applied papers often are used in ways that might not lead to citations. BRIDGES transitioned to a new format in September 2009 to address new types of complex, multifaceted linkages. All new BRIDGES articles will be open access, and authors will be encouraged to produce lay-language fact sheets and to post them on the web.

5 CFR 536.206 - Determining an employee's rate of basic pay under grade retention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Determining an employee's rate of basic... employee's rate of basic pay under grade retention. (a) General. (1) When an employee becomes entitled to... determine the employee's rate of basic pay. (2) This section does not apply to an employee whose entitlement...

Can Basic Research on Children and Families Be Useful for the Policy Process?

ERIC Educational Resources Information Center

Moore, Kristin A.

Based on the assumption that basic science is the crucial building block for technological and biomedical progress, this paper examines the relevance for public policy of basic demographic and behavioral sciences research on children and families. The characteristics of basic research as they apply to policy making are explored. First, basic…

Basic Electronics I.

ERIC Educational Resources Information Center

Robertson, L. Paul

Designed for use in basic electronics programs, this curriculum guide is comprised of twenty-nine units of instruction in five major content areas: Orientation, Basic Principles of Electricity/Electronics, Fundamentals of Direct Current, Fundamentals of Alternating Current, and Applying for a Job. Each instructional unit includes some or all of…

Symbolic Interaction and Applied Social Research

PubMed Central

Kotarba, Joseph A.

2014-01-01

In symbolic interaction, a traditional yet unfortunate and unnecessary distinction has been made between basic and applied research. The argument has been made that basic research is intended to generate new knowledge, whereas applied research is intended to apply knowledge to the solution of practical (social and organizational) problems. I will argue that the distinction between basic and applied research in symbolic interaction is outdated and dysfunctional. The masters of symbolic interactionist thought have left us a proud legacy of shaping their scholarly thinking and inquiry in response to and in light of practical issues of the day (e.g., Znaniecki, and Blumer). Current interactionist work continues this tradition in topical areas such as social justice studies. Applied research, especially in term of evaluation and needs assessment studies, can be designed to serve both basic and applied goals. Symbolic interaction provides three great resources to do this. The first is its orientation to dynamic sensitizing concepts that direct research and ask questions instead of supplying a priori and often impractical answers. The second is its orientation to qualitative methods, and appreciation for the logic of grounded theory. The third is interactionism’s overall holistic approach to interfacing with the everyday life world. The primary illustrative case here is the qualitative component of the evaluation of an NIH-funded, translational medical research program. The qualitative component has provided interactionist-inspired insights into translational research, such as examining cultural change in medical research in terms of changes in the form and content of formal and informal discourse among scientists; delineating the impact of significant symbols such as "my lab" on the social organization of science; and appreciating the essence of the self-concept "scientist" on the increasingly bureaucratic and administrative identities of medical researchers. This component has also contributed to the basic social scientific literature on complex organizations and the self. PMID:25221375

Symbolic Interaction and Applied Social Research: A FOCUS ON TRANSLATIONAL SCIENCE RESEARCH1.

PubMed

Kotarba, Joseph A

2014-08-01

In symbolic interaction, a traditional yet unfortunate and unnecessary distinction has been made between basic and applied research. The argument has been made that basic research is intended to generate new knowledge, whereas applied research is intended to apply knowledge to the solution of practical (social and organizational) problems. I will argue that the distinction between basic and applied research in symbolic interaction is outdated and dysfunctional. The masters of symbolic interactionist thought have left us a proud legacy of shaping their scholarly thinking and inquiry in response to and in light of practical issues of the day (e.g., Znaniecki, and Blumer). Current interactionist work continues this tradition in topical areas such as social justice studies. Applied research, especially in term of evaluation and needs assessment studies, can be designed to serve both basic and applied goals. Symbolic interaction provides three great resources to do this. The first is its orientation to dynamic sensitizing concepts that direct research and ask questions instead of supplying a priori and often impractical answers. The second is its orientation to qualitative methods, and appreciation for the logic of grounded theory. The third is interactionism's overall holistic approach to interfacing with the everyday life world. The primary illustrative case here is the qualitative component of the evaluation of an NIH-funded, translational medical research program. The qualitative component has provided interactionist-inspired insights into translational research, such as examining cultural change in medical research in terms of changes in the form and content of formal and informal discourse among scientists; delineating the impact of significant symbols such as "my lab" on the social organization of science; and appreciating the essence of the self-concept "scientist" on the increasingly bureaucratic and administrative identities of medical researchers. This component has also contributed to the basic social scientific literature on complex organizations and the self.

Cost Reporting at a Navy Branch Clinic

DTIC Science & Technology

1993-03-01

John Wiley & Sons, 1991. 15 Horngren , Charles, Cost Accounting -=A Managerial Emphasis, 5th Edition, Prentice Hall, Inc., Englewood Cliffs, N.J., 1982...traditionally reported under a partial cost reporting system. By applying basic principles of managerial accounting , a full cost reporting system is...traditionally reported under a partial cost reporting system. By applying basic principles of managerial accounting , a proposed full cost reporting

Discordance between bovine leukemia virus tax immortalization in vitro and oncogenicity in vivo.

PubMed

Twizere, J C; Kerkhofs, P; Burny, A; Portetelle, D; Kettmann, R; Willems, L

2000-11-01

Bovine leukemia virus (BLV) Tax protein, a transcriptional activator of viral expression, is essential for viral replication in vivo. Tax is believed to be involved in leukemogenesis because of its second function, immortalization of primary cells in vitro. These activities of Tax can be dissociated on the basis of point mutations within specific regions of the protein. For example, mutation of the phosphorylation sites at serines 106 and 293 abrogates immortalization potential in vitro but maintains transcriptional activity. This type of mutant is thus particularly useful for unraveling the role of Tax immortalization activity during leukemogenesis independently of viral replication. In this report, we describe the biological properties of BLV recombinant proviruses mutated in the Tax phosphorylation sites (BLVTax106+293). Titration of the proviral loads by semiquantitative PCR revealed that the BLV mutants propagated at wild-type levels in vivo. Furthermore, two animals (sheep 480 and 296) infected with BLVTax106+293 developed leukemia or lymphosarcoma after 16 and 36 months, respectively. These periods of time are within the normal range of latencies preceding the onset of pathogenesis induced by wild-type viruses. The phenotype of the mutant-infected cells was characteristic of a B lymphocyte (immunoglobulin M positive) expressing CD11b and CD5 (except at the final stage for the latter marker), a pattern that is typical of wild-type virus-infected target cells. Interestingly, the transformed B lymphocytes from sheep 480 also coexpressed the CD8 marker, a phenotype rarely observed in tumor biopsies from chronic lymphocytic leukemia patients. Finally, direct sequencing of the tax gene demonstrated that the leukemic cells did not harbor revertant proviruses. We conclude that viruses expressing a Tax mutant unable to transform primary cells in culture are still pathogenic in the sheep animal model. Our data thus provide a clear example of the discordant conclusions that can be drawn from in vitro immortalization assays and in vivo experiments. These observations could be of interest for other systems, such as the related human T-cell leukemia virus type 1, which currently lack animal models allowing the study of the leukemogenic process.

How do scientists respond to anomalies? Different strategies used in basic and applied science.

PubMed

Trickett, Susan Bell; Trafton, J Gregory; Schunn, Christian D

2009-10-01

We conducted two in vivo studies to explore how scientists respond to anomalies. Based on prior research, we identify three candidate strategies: mental simulation, mental manipulation of an image, and comparison between images. In Study 1, we compared experts in basic and applied domains (physics and meteorology). We found that the basic scientists used mental simulation to resolve an anomaly, whereas applied science practitioners mentally manipulated the image. In Study 2, we compared novice and expert meteorologists. We found that unlike experts, novices used comparison to address anomalies. We discuss the nature of expertise in the two kinds of science, the relationship between the type of science and the task performed, and the relationship of the strategies investigated to scientific creativity. Copyright © 2009 Cognitive Science Society, Inc.

Introduction to Welding.

ERIC Educational Resources Information Center

Fortney, Clarence; Gregory, Mike

This curriculum guide provides six units of instruction on basic welding. Addressed in the individual units of instruction are the following topics: employment opportunities for welders, welding safety and first aid, welding tools and equipment, basic metals and metallurgy, basic math and measuring, and procedures for applying for a welding job.…

E-Basics: Online Basic Training in Program Evaluation

ERIC Educational Resources Information Center

Silliman, Ben

2016-01-01

E-Basics is an online training in program evaluation concepts and skills designed for youth development professionals, especially those working in nonformal science education. Ten hours of online training in seven modules is designed to prepare participants for mentoring and applied practice, mastery, and/or team leadership in program evaluation.…

Basic Skills in Asian Studies: India.

ERIC Educational Resources Information Center

Hantula, James

Designed for an Asian studies program at the secondary level and using learning activities centering on India, the guide develops four basic skills: reading, applying critical thinking, interpreting the geography, and understanding history. Five learning activities are provided for each basic skill and each unit is introduced with a description…

5 CFR 841.703 - Increases on basic annuities and survivor annuities.

Code of Federal Regulations, 2012 CFR

2012-01-01

....704, 841.706, and 841.707, and paragraph (e) of this section, COLA's on basic annuities and survivor... percentage change. (b) After survivor annuities commence, they are subject to COLA's computed under paragraph... component. (c) COLA's apply to basic annuities (not to annuity supplements), survivor annuities, and...

5 CFR 841.703 - Increases on basic annuities and survivor annuities.

Code of Federal Regulations, 2013 CFR

2013-01-01

....704, 841.706, and 841.707, and paragraph (e) of this section, COLA's on basic annuities and survivor... percentage change. (b) After survivor annuities commence, they are subject to COLA's computed under paragraph... component. (c) COLA's apply to basic annuities (not to annuity supplements), survivor annuities, and...

5 CFR 841.703 - Increases on basic annuities and survivor annuities.

Code of Federal Regulations, 2014 CFR

2014-01-01

....704, 841.706, and 841.707, and paragraph (e) of this section, COLA's on basic annuities and survivor... percentage change. (b) After survivor annuities commence, they are subject to COLA's computed under paragraph... component. (c) COLA's apply to basic annuities (not to annuity supplements), survivor annuities, and...

Welding As Science: Applying Basic Engineering Principles to the Discipline

NASA Technical Reports Server (NTRS)

Nunes, A. C., Jr.

2010-01-01

This Technical Memorandum provides sample problems illustrating ways in which basic engineering science has been applied to the discipline of welding. Perhaps inferences may be drawn regarding optimal approaches to particular welding problems, as well as for the optimal education for welding engineers. Perhaps also some readers may be attracted to the science(s) of welding and may make worthwhile contributions to the discipline.

48 CFR 35.001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.001 Definitions. Applied research means the effort that (a) normally follows basic research, but may not be severable from the related basic research; (b) attempts to...

Cell cycle control in acute myeloid leukemia

PubMed Central

Schnerch, Dominik; Yalcintepe, Jasmin; Schmidts, Andrea; Becker, Heiko; Follo, Marie; Engelhardt, Monika; Wäsch, Ralph

2012-01-01

Acute myeloid leukemia (AML) is the result of a multistep transforming process of hematopoietic precursor cells (HPCs) which enables them to proceed through limitless numbers of cell cycles and to become resistant to cell death. Increased proliferation renders these cells vulnerable to acquiring mutations and may favor leukemic transformation. Here, we review how deregulated cell cycle control contributes to increased proliferation in AML and favors genomic instability, a prerequisite to confer selective advantages to particular clones in order to adapt and independently proliferate in the presence of a changing microenvironment. We discuss the connection between differentiation and proliferation with regard to leukemogenesis and outline the impact of specific alterations on response to therapy. Finally, we present examples, how a better understanding of cell cycle regulation and deregulation has already led to new promising therapeutic strategies. PMID:22957304

In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

PubMed Central

Miller, Peter G.; Al-Shahrour, Fatima; Hartwell, Kimberly A.; Chu, Lisa P.; Järås, Marcus; Puram, Rishi V.; Puissant, Alexandre; Callahan, Kevin P.; Ashton, John; McConkey, Marie E.; Poveromo, Luke P.; Cowley, Glenn S.; Kharas, Michael G.; Labelle, Myriam; Shterental, Sebastian; Fujisaki, Joji; Silberstein, Lev; Alexe, Gabriela; Al-Hajj, Muhammad A.; Shelton, Christopher A.; Armstrong, Scott A.; Root, David E.; Scadden, David T.; Hynes, Richard O.; Mukherjee, Siddhartha; Stegmaier, Kimberly; Jordan, Craig T.; Ebert, Benjamin L.

2013-01-01

SUMMARY We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. PMID:23770013

Is alkaline phosphatase the smoking gun for highly refractory primitive leukemic cells?

PubMed Central

Rico, Laura G.; Juncà, Jordi; Ward, Mike D.; Bradford, Jolene; Petriz, Jordi

2016-01-01

With the aim to detect candidate malignant primitive progenitor populations, we modified an original alkaline phosphatase (ALP) stem cell detection method based on the identification of alkaline phosphatase fluorescent cells in combination with flow cytometry immunophenotyping. Over a period of one year, we have been using this technique to study its activity in patients with leukemia and lymphoma, showing that changes in the alkaline phosphatase levels can be used to detect rare populations of highly refractory malignant cells. By screening different blood cancers, we have observed that this activity is not always restricted to CD34+ leukemic cells, and can be overexpressed in CD34 negative leukemia. We have verified that this method gives accurate and reproducible measurements and our preliminary results suggest that CD34+/ALPhigh cells appear to sustain leukemogenesis over time. PMID:27732563

Current Health Problems.

ERIC Educational Resources Information Center

Gay, John; And Others

The basic premise of this text is that, in addition to the presentation of basic cognitive and affective information, health education should go one step further by assisting student in developing decision-making skills. The text begins by offering the student a basic foundation of what is meant by health and how this meaning applies to the world,…

A Simulation for Teaching the Basic and Clinical Science of Fluid Therapy

ERIC Educational Resources Information Center

Rawson, Richard E.; Dispensa, Marilyn E.; Goldstein, Richard E.; Nicholson, Kimberley W.; Vidal, Noni Korf

2009-01-01

The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical…

Connecting Science and Society: Basic Research in the Service of Social Objectives

NASA Astrophysics Data System (ADS)

Sonnert, Gerhard

2007-03-01

A flawed dichotomy of basic versus applied science (or of ``curiosity-driven'' vs. ``mission-oriented'' science) pervades today's thinking about science policy. This talk argues for the addition of a third mode of scientific research, called Jeffersonian science. Whereas basic science, as traditionally understood, is a quest for the unknown regardless of societal needs, and applied science is known science applied to known needs, Jeffersonian science is the quest for the unknown in the service of a known social need. It is research in an identified area of basic scientific ignorance that lies at the heart of a social problem. The talk discusses the conceptual foundations and then provides some case examples of Jeffersonian-type science initiatives, such as the Lewis and Clark Expedition, initiated by Thomas Jefferson (which led us to call this mode of research Jeffersonian), research conducted under the auspices of the National Institutes of Health, and a science policy project by President Jimmy Carter and his Science Adviser, Frank Press, in the late 1970s. Because the concept of Jeffersonian science explicitly ties basic research to the social good, one of the potential benefits of adding a Jeffersonian dimension to our thinking about science is that it might make science careers more attractive to women and underrepresented minorities.

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ.

PubMed

Di Matteo, A; Franceschini, M; Paiardini, A; Grottesi, A; Chiarella, S; Rocchio, S; Di Natale, C; Marasco, D; Vitagliano, L; Travaglini-Allocatelli, C; Federici, L

2017-09-18

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment.

A Robust Error Model for iTRAQ Quantification Reveals Divergent Signaling between Oncogenic FLT3 Mutants in Acute Myeloid Leukemia*

PubMed Central

Zhang, Yi; Askenazi, Manor; Jiang, Jingrui; Luckey, C. John; Griffin, James D.; Marto, Jarrod A.

2010-01-01

The FLT3 receptor tyrosine kinase plays an important role in normal hematopoietic development and leukemogenesis. Point mutations within the activation loop and in-frame tandem duplications of the juxtamembrane domain represent the most frequent molecular abnormalities observed in acute myeloid leukemia. Interestingly these gain-of-function mutations correlate with different clinical outcomes, suggesting that signals from constitutive FLT3 mutants activate different downstream targets. In principle, mass spectrometry offers a powerful means to quantify protein phosphorylation and identify signaling events associated with constitutively active kinases or other oncogenic events. However, regulation of individual phosphorylation sites presents a challenging case for proteomics studies whereby quantification is based on individual peptides rather than an average across different peptides derived from the same protein. Here we describe a robust experimental framework and associated error model for iTRAQ-based quantification on an Orbitrap mass spectrometer that relates variance of peptide ratios to mass spectral peak height and provides for assignment of p value, q value, and confidence interval to every peptide identification, all based on routine measurements, obviating the need for detailed characterization of individual ion peaks. Moreover, we demonstrate that our model is stable over time and can be applied in a manner directly analogous to ubiquitously used external mass calibration routines. Application of our error model to quantitative proteomics data for FLT3 signaling provides evidence that phosphorylation of tyrosine phosphatase SHP1 abrogates the transformative potential, but not overall kinase activity, of FLT3-D835Y in acute myeloid leukemia. PMID:20019052

On applying cognitive psychology.

PubMed

Baddeley, Alan

2013-11-01

Recent attempts to assess the practical impact of scientific research prompted my own reflections on over 40 years worth of combining basic and applied cognitive psychology. Examples are drawn principally from the study of memory disorders, but also include applications to the assessment of attention, reading, and intelligence. The most striking conclusion concerns the many years it typically takes to go from an initial study, to the final practical outcome. Although the complexity and sheer timescale involved make external evaluation problematic, the combination of practical satisfaction and theoretical stimulation make the attempt to combine basic and applied research very rewarding. © 2013 The British Psychological Society.

Coal-seismic, desktop computer programs in BASIC; Part 6, Develop rms velocity functions and apply mute and normal movement

USGS Publications Warehouse

Hasbrouck, W.P.

1983-01-01

Processing of data taken with the U.S. Geological Survey's coal-seismic system is done with a desktop, stand-alone computer. Programs for this computer are written in the extended BASIC language utilized by the Tektronix 4051 Graphic System. This report presents computer programs used to develop rms velocity functions and apply mute and normal moveout to a 12-trace seismogram.

40 CFR 60.140 - Applicability and designation of affected facility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Performance for Primary Emissions from Basic Oxygen Process Furnaces for Which Construction is Commenced After... which the provisions of this subpart apply is each basic oxygen process furnace. (b) Any facility under...

40 CFR 60.140 - Applicability and designation of affected facility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Performance for Primary Emissions from Basic Oxygen Process Furnaces for Which Construction is Commenced After... which the provisions of this subpart apply is each basic oxygen process furnace. (b) Any facility under...

40 CFR 60.140 - Applicability and designation of affected facility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Performance for Primary Emissions from Basic Oxygen Process Furnaces for Which Construction is Commenced After... which the provisions of this subpart apply is each basic oxygen process furnace. (b) Any facility under...

40 CFR 60.140 - Applicability and designation of affected facility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Performance for Primary Emissions from Basic Oxygen Process Furnaces for Which Construction is Commenced After... which the provisions of this subpart apply is each basic oxygen process furnace. (b) Any facility under...

40 CFR 60.140 - Applicability and designation of affected facility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Performance for Primary Emissions from Basic Oxygen Process Furnaces for Which Construction is Commenced After... which the provisions of this subpart apply is each basic oxygen process furnace. (b) Any facility under...

What is Basic Research? Insights from Historical Semantics.

PubMed

Schauz, Désirée

2014-01-01

For some years now, the concept of basic research has been under attack. Yet although the significance of the concept is in doubt, basic research continues to be used as an analytical category in science studies. But what exactly is basic research? What is the difference between basic and applied research? This article seeks to answer these questions by applying historical semantics. I argue that the concept of basic research did not arise out of the tradition of pure science. On the contrary, this new concept emerged in the late 19th and early 20th centuries, a time when scientists were being confronted with rising expectations regarding the societal utility of science. Scientists used the concept in order to try to bridge the gap between the promise of utility and the uncertainty of scientific endeavour. Only after 1945, when United States science policy shaped the notion of basic research, did the concept revert to the older ideals of pure science. This revival of the purity discourse was caused by the specific historical situation in the US at that time: the need to reform federal research policy after the Second World War, the new dimension of ethical dilemmas in science and technology during the atomic era, and the tense political climate during the Cold War.

Intelligent Management Control for Unmanned Aircraft Navigation and Formation Keeping

DTIC Science & Technology

2003-06-01

support of a variety of military and civilian applications has introduced basic and applied research challenges in areas such as levels of autonomy and...methodologies based on reliable and advanced basic research results. The present paper outlines some of these aspects, although not in an exhaustive manner...takes ∆P’ as input. Figure 3 shows the complete control block diagram. The resulting control law is: ∆T = KFC (s)∆ The FC applies the corrections ∆T

A crash course on data analysis in asteroseismology

NASA Astrophysics Data System (ADS)

Appourchaux, Thierry

2014-02-01

In this course, I try to provide a few basics required for performing data analysis in asteroseismology. First, I address how one can properly treat times series: the sampling, the filtering effect, the use of Fourier transform, the associated statistics. Second, I address how one can apply statistics for decision making and for parameter estimation either in a frequentist of a Bayesian framework. Last, I review how these basic principle have been applied (or not) in asteroseismology.

45 CFR 263.9 - May a State avoid a penalty for failing to meet the basic MOE requirement through reasonable...

Code of Federal Regulations, 2010 CFR

2010-10-01

... the basic MOE requirement through reasonable cause or corrective compliance? 263.9 Section 263.9... FEDERAL TANF FUNDS What Rules Apply to a State's Maintenance of Effort? § 263.9 May a State avoid a penalty for failing to meet the basic MOE requirement through reasonable cause or corrective compliance...

12 CFR 900.1 - Basic terms relating to the Finance Board, the Bank System and related entities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Basic terms relating to the Finance Board, the Bank System and related entities. 900.1 Section 900.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.1 Basic terms...

12 CFR 900.1 - Basic terms relating to the Finance Board, the Bank System and related entities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Basic terms relating to the Finance Board, the Bank System and related entities. 900.1 Section 900.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.1 Basic terms...

12 CFR 900.1 - Basic terms relating to the Finance Board, the Bank System and related entities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Basic terms relating to the Finance Board, the Bank System and related entities. 900.1 Section 900.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.1 Basic terms...

12 CFR 900.1 - Basic terms relating to the Finance Board, the Bank System and related entities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Basic terms relating to the Finance Board, the Bank System and related entities. 900.1 Section 900.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.1 Basic terms...

77 FR 74616 - Amendments and Correction to Petitions for Waiver and Interim Waiver for Consumer Products and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... decision and order must be used for all future testing for any basic models covered by the decision and... require petitioners to: (1) Specify the basic model(s) to which the waiver applies; (2) identify other manufacturers of similar products; (3) include any known alternate test procedures of the basic model, with the...

10 CFR 600.314 - Program income.

Code of Federal Regulations, 2010 CFR

2010-01-01

...)(3) of this section applies automatically to all projects or programs except research. For awards that support basic or applied research, paragraph (d)(1) of this section applies automatically unless... Program income. (a) DOE must apply the standards in this section to the disposition of program income from...

The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias

PubMed Central

Masetti, Riccardo; Serravalle, Salvatore; Biagi, Carlotta; Pession, Andrea

2011-01-01

Acute leukemia is the most common type of childhood and adolescence cancer, characterized by clonal proliferation of variably differentiated myeloid or lymphoid precursors. Recent insights into the molecular pathogenesis of leukemia have shown that epigenetic modifications, such as deacetylation of histones and DNA methylation, play crucial roles in leukemogenesis, by transcriptional silencing of critical genes. Histone deacetylases (HDACs) are potential targets in the treatment of leukaemia, and, as a consequence, inhibitors of HDACs (HDIs) are being studied for therapeutic purposes. HDIs promote or enhance several different anticancer mechanisms, such as apoptosis, cell cycle arrest, and cellular differentiation and, therefore, are in evidence as promising treatment for children and adolescents with acute leukemia, in monotherapy or in association with other anticancer drugs. Here we review the main preclinical and clinical studies regarding the use of HDIs in treating childhood and adolescence leukemia. PMID:21318168

Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity.

PubMed

Hope, Kristin J; Jin, Liqing; Dick, John E

2004-07-01

Emerging evidence suggests cancer stem cells sustain neoplasms; however, little is understood of the normal cell initially targeted and the resultant cancer stem cells. We show here, by tracking individual human leukemia stem cells (LSCs) in nonobese diabetic-severe combined immunodeficiency mice serially transplanted with acute myeloid leukemia cells, that LSCs are not functionally homogeneous but, like the normal hematopoietic stem cell (HSC) compartment, comprise distinct hierarchically arranged LSC classes. Distinct LSC fates derived from heterogeneous self-renewal potential. Some LSCs emerged only in recipients of serial transplantation, indicating they divided rarely and underwent self-renewal rather than commitment after cell division within primary recipients. Heterogeneity in LSC self-renewal potential supports the hypothesis that they derive from normal HSCs. Furthermore, normal developmental processes are not completely abolished during leukemogenesis. The existence of multiple stem cell classes shows the need for LSC-targeted therapies.

Therapeutic targeting of HES1 transcriptional programs in T-ALL

PubMed Central

Schnell, Stephanie A.; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Belver, Laura; Xu, Luyao; Qin, Yue; Kageyama, Ryoichiro

2015-01-01

Oncogenic activation of NOTCH1 signaling plays a central role in the pathogenesis of T-cell acute lymphoblastic leukemia, with mutations on this signaling pathway affecting more than 60% of patients at diagnosis. However, the transcriptional regulatory circuitries driving T-cell transformation downstream of NOTCH1 remain incompletely understood. Here we identify Hairy and Enhancer of Split 1 (HES1), a transcriptional repressor controlled by NOTCH1, as a critical mediator of NOTCH1-induced leukemogenesis strictly required for tumor cell survival. Mechanistically, we demonstrate that HES1 directly downregulates the expression of BBC3, the gene encoding the PUMA BH3-only proapoptotic factor in T-cell acute lymphoblastic leukemia. Finally, we identify perhexiline, a small-molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1-induced leukemias in vitro and in vivo. PMID:25784680

Stem cell exhaustion due to Runx1 deficiency is prevented by Evi5 activation in leukemogenesis

PubMed Central

Jacob, Bindya; Yamashita, Namiko; Wang, Chelsia Qiuxia; Taniuchi, Ichiro; Littman, Dan R.; Asou, Norio

2010-01-01

The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1−/− mice do not develop spontaneous leukemia. Here we show that maintenance of Runx1−/− HSCs is compromised, progressively resulting in HSC exhaustion. In leukemia development, the stem cell exhaustion was rescued by additional genetic changes. Retroviral insertional mutagenesis revealed Evi5 activation as a cooperating genetic alteration and EVI5 overexpression indeed prevented Runx1−/− HSC exhaustion in mice. Moreover, EVI5 was frequently overexpressed in human RUNX1-related leukemias. These results provide insights into the mechanism for maintenance of pre-leukemic stem cells and may provide a novel direction for therapeutic applications. PMID:20008790

Expression and role of DJ-1 in leukemia

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

Liu Hang; Wang Min; Li Min

2008-10-24

DJ-1 is a multifunctional protein that has been implicated in pathogenesis of some solid tumors. In this study, we found that DJ-1 was overexpressed in acute leukemia (AL) patient samples and leukemia cell lines, which gave the first clue that DJ-1 overexpression might be involved in leukemogenesis and/or disease progression of AL. Inactivation of DJ-1 by RNA-mediated interference (RNAi) in leukemia cell lines K562 and HL60 resulted in inhibition of the proliferation potential and enhancement of the sensitivity of leukemia cells to chemotherapeutic drug etoposide. Further investigation of DJ-1 activity revealed that phosphatase and tensin homolog (PTEN), as well asmore » some proliferation and apoptosis-related genes, was regulated by DJ-1. Thus, DJ-1 might be involved in leukemogesis through regulating cell growth, proliferation, and apoptosis. It could be a potential therapeutic target for leukemia.« less

Genetic loss of SH2B3 in acute lymphoblastic leukemia.

PubMed

Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K; Ferrando, Adolfo A

2013-10-03

The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis.

Emerging therapeutic targets in human acute myeloid leukemia (part 2) - bromodomain inhibition should be considered as a possible strategy for various patient subsets.

PubMed

Reikvam, Håkon; Hoang, Tuyen Thi van; Bruserud, Øystein

2015-06-01

The recent advances in our understanding of leukemogenesis have clearly demonstrated that human acute myeloid leukemia is a heterogeneous malignancy, and several disease mechanisms should probably be regarded as possible therapeutic targets only for specific subsets of patients and not for acute myeloid leukemia in general. One promising strategy for epigenetic targeting is inhibition of the binding between bromodomain-containing transcription regulators and acetylated lysine residues on histones. This possible approach has been investigated especially for patients with 11q23 and chromosome 8 abnormalities. An alternative target is the histone methyltransferase COT1L. Major challenges for both approaches will be to clarify how these strategies should be combined with each other or with conventional chemotherapy, and whether their use should be limited to certain subsets of patients.

Calls for Canada to support basic research

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2017-08-01

Canada’s decade-long shift of financial support from fundamental studies towards applied research is dismantling the nation’s funding of basic science, according to a report by the Global Young Academy (GYA) - an international society of young scientists.

Applied Electronics and Optical Laboratory: an optimized practical course for comprehensive training on optics and electronics

NASA Astrophysics Data System (ADS)

Wang, Kaiwei; Wang, Xiaoping

2017-08-01

In order to enhance the practical education and hands-on experience of optoelectronics and eliminate the overlapping contents that previously existed in the experiments section adhering to several different courses, a lab course of "Applied Optoelectronics Laboratory" has been established in the College of Optical Science and Engineering, Zhejiang University. The course consists of two sections, i.e., basic experiments and project design. In section 1, basic experiments provide hands-on experience with most of the fundamental concept taught in the corresponding courses. These basic experiments including the study of common light sources such as He-Ne laser, semiconductor laser and solid laser and LED; the testing and analysis of optical detectors based on effects of photovoltaic effect, photoconduction effect, photo emissive effect and array detectors. In section 2, the course encourages students to build a team and establish a stand-alone optical system to realize specific function by taking advantage of the basic knowledge learned from section 1. Through these measures, students acquired both basic knowledge and the practical application skills. Moreover, interest in science has been developed among students.

Technology | FNLCR Staging

Cancer.gov

The Frederick National Lab develops and applies advanced, next-generation technologies to solve basic and applied problems in the biomedical sciences, and serves as a national resource of shared high-tech facilities.

Improving basic math skills through integrated dynamic representation strategies.

PubMed

González-Castro, Paloma; Cueli, Marisol; Cabeza, Lourdes; Álvarez-García, David; Rodríguez, Celestino

2014-01-01

In this paper, we analyze the effectiveness of the Integrated Dynamic Representation strategy (IDR) to develop basic math skills. The study involved 72 students, aged between 6 and 8 years. We compared the development of informal basic skills (numbers, comparison, informal calculation, and informal concepts) and formal (conventionalisms, number facts, formal calculus, and formal concepts) in an experimental group (n = 35) where we applied the IDR strategy and in a Control group (n = 37) in order to identify the impact of the procedure. The experimental group improved significantly in all variables except for number facts and formal calculus. It can therefore be concluded that IDR favors the development of the skills more closely related to applied mathematics than those related to automatic mathematics and mental arithmetic.

Basic principles, methodology, and applications of remote sensing in agriculture

NASA Technical Reports Server (NTRS)

Moreira, M. A. (Principal Investigator); Deassuncao, G. V.

1984-01-01

The basic principles of remote sensing applied to agriculture and the methods used in data analysis are described. Emphasis is placed on the importance of developing a methodology that may help crop forecast, basic concepts of spectral signatures of vegetation, the methodology of the LANDSAT data utilization in agriculture, and the remote sensing program application of INPE (Institute for Space Research) in agriculture.

Cognitively-Related Basic Activities of Daily Living Impairment Greatly Increases the Risk of Death in Alzheimers Disease.

PubMed

Liang, Fu-Wen; Chan, Wenyaw; Chen, Ping-Jen; Zimmerman, Carissa; Waring, Stephen; Doody, Rachelle

2016-01-01

Some Alzheimer's disease (AD) patients die without ever developing cognitively impaired basic activities of daily living (basic ADL), which may reflect slower disease progression or better compensatory mechanisms. Although impaired basic ADL is related to disease severity, it may exert an independent risk for death. This study examined the association between impaired basic ADL and survival of AD patients, and proposed a multistate approach for modeling the time to death for patients who demonstrate different patterns of progression of AD that do or do not include basic ADL impairment. 1029 patients with probable AD at the Baylor College of Medicine Alzheimer's Disease and Memory Disorders Center met the criteria for this study. Two complementary definitions were used to define development of basic ADL impairment using the Physical Self-Maintenance Scale score. A weighted Cox regression model, including a time-dependent covariate (development of basic ADL impairment), and a multistate survival model were applied to examine the effect of basic ADL impairment on survival. As expected decreased ability to perform basic ADL at baseline, age at initial visit, years of education, and sex were all associated with significantly higher mortality risk. In those unimpaired at baseline, the development of basic ADL impairment was also associated with a much greater risk of death (hazard ratios 1.77-4.06) over and above the risk conferred by loss of MMSE points. A multi-state Cox model, controlling for those other variables quantified the substantive increase in hazard ratios for death conferred by the development of basic ADL impairment by two definitions and can be applied to calculate the short term risk of mortality in individual patients. The current study demonstrates that the presence of basic ADL impairment or the development of such impairments are important predictors of death in AD patients, regardless of severity.

The applied importance of research on the matching law

PubMed Central

Pierce, W. David; Epling, W. Frank

1995-01-01

In this essay, we evaluate the applied implications of two articles related to the matching law and published in the Journal of the Experimental Analysis of Behavior, May 1994. Building on Mace's (1994) criteria for increasing the applied relevance of basic research, we evaluate the applied implications of basic research studies. Research by Elsmore and McBride (1994) and Savastano and Fantino (1994) involve an extension of the behavioral model of choice. Elsmore and McBride used rats as subjects, but arranged a multioperant environment that resembles some of the complex contingencies of human behavior. Savastino and Fantino used human subjects and extended the matching law to ratio and interval contingencies. These experiments contribute to a growing body of knowledge on the matching law and its relevance for human behavior. PMID:16795866

Biomedical research, development, and engineering at the Johns Hopkins University Applied Physics Laboratory. Annual report 1 October 1978-30 September 1979

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

Not Available

The Medical Institutions of The Johns Hopkins University and The Johns Hopkins University Applied Physics Laboratory have developed a vigorous collaborative program of biomedical research, development, and systems engineering. An important objective of the program is to apply the expertise in engineering, the physical sciences, and systems analysis acquired by APL in defense and space research and development to problems of medical research and health care delivery. This program has grown to include collaboration with many of the clinical and basic science departments of the medical divisions. Active collaborative projects exist in ophthalmology, neurosensory research and instrumentation development, cardiovascular systems,more » patient monitoring, therapeutic and rehabilitation systems, clinical information systems, and clinical engineering. This application of state-of-the-art technology has contributed to advances in many areas of basic medical research and in clinical diagnosis and therapy through improvement of instrumentation, techniques, and basic understanding.« less

Currency arbitrage detection using a binary integer programming model

NASA Astrophysics Data System (ADS)

Soon, Wanmei; Ye, Heng-Qing

2011-04-01

In this article, we examine the use of a new binary integer programming (BIP) model to detect arbitrage opportunities in currency exchanges. This model showcases an excellent application of mathematics to the real world. The concepts involved are easily accessible to undergraduate students with basic knowledge in Operations Research. Through this work, students can learn to link several types of basic optimization models, namely linear programming, integer programming and network models, and apply the well-known sensitivity analysis procedure to accommodate realistic changes in the exchange rates. Beginning with a BIP model, we discuss how it can be reduced to an equivalent but considerably simpler model, where an efficient algorithm can be applied to find the arbitrages and incorporate the sensitivity analysis procedure. A simple comparison is then made with a different arbitrage detection model. This exercise helps students learn to apply basic Operations Research concepts to a practical real-life example, and provides insights into the processes involved in Operations Research model formulations.

Ionizing Radiation–Inducible miR-27b Suppresses Leukemia Proliferation via Targeting Cyclin A2

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

Wang, Bo; Li, Dongping; Kovalchuk, Anna

2014-09-01

Purpose: Ionizing radiation is a common carcinogen that is important for the development of leukemia. However, the underlying epigenetic mechanisms remain largely unknown. The goal of the study was to explore microRNAome alterations induced by ionizing radiation (IR) in murine thymus, and to determine the role of IR-inducible microRNA (miRNA/miR) in the development of leukemia. Methods and Materials: We used the well-established C57BL/6 mouse model and miRNA microarray profiling to identify miRNAs that are differentially expressed in murine thymus in response to irradiation. TIB152 human leukemia cell line was used to determine the role of estrogen receptor–α (ERα) in miR-27bmore » transcription. The biological effects of ectopic miR-27b on leukemogenesis were measured by western immunoblotting, cell viability, apoptosis, and cell cycle analyses. Results: Here, we have shown that IR triggers the differential expression of miR-27b in murine thymus tissue in a dose-, time- and sex-dependent manner. miR-27b was significantly down-regulated in leukemia cell lines CCL119 and TIB152. Interestingly, ERα was overexpressed in those 2 cell lines, and it was inversely correlated with miR-27b expression. Therefore, we used TIB152 as a model system to determine the role of ERα in miR-27b expression and the contribution of miR-27b to leukemogenesis. β-Estradiol caused a rapid and transient reduction in miR-27b expression reversed by either ERα-neutralizing antibody or ERK1/2 inhibitor. Ectopic expression of miR-27b remarkably suppressed TIB152 cell proliferation, at least in part, by inducing S-phase arrest. In addition, it attenuated the expression of cyclin A2, although it had no effect on the levels of PCNA, PPARγ, CDK2, p21, p27, p-p53, and cleaved caspase-3. Conclusion: Our data reveal that β-estradiol/ERα signaling may contribute to the down-regulation of miR-27b in acute leukemia cell lines through the ERK1/2 pathway, and that miR-27b may function as a tumor suppressor that inhibits cell proliferation by targeting cyclin A2.« less

76 FR 14977 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... surveillance programs; (5) conducts epidemiologic, and basic and applied laboratory research to identify new... enhance antimicrobial resistance prevention and control, surveillance and response, and applied research..., response, surveillance, applied research, health communication, and public policy; and (15) advises the...

English: Basic Mechanics Modules 4 and 5.

ERIC Educational Resources Information Center

Pipeline, 1983

1983-01-01

"English: Basic Mechanics" is a series of computer-based lessons for the Apple II that allow students to practice applying the fundamentals of English grammar and punctuation. The two newest modules covering use of subordinate clauses and use of subordinate phrases are described. (JN)

Electromembrane extraction using two separate cells: A new design for simultaneous extraction of acidic and basic compounds.

PubMed

Nojavan, Saeed; Asadi, Sakine

2016-02-01

Simultaneous extraction of acidic and basic analytes from a sample is seen to be a challenging task. In this work, a novel and efficient electromembrane extraction (EME) method based on two separate cells was applied to simultaneously extract and preconcentrate two acidic drugs (naproxen and ibuprofen) along with a basic drug (ketamine). Once both cells were filled with the sample solution, basic drug was extracted from one cell with the other cell used to extract acidic drugs. The employed supported liquid membranes for the extraction of acidic and basic drugs were 2-ethyl hexanol and 1-octanol, respectively. Under an applied potential of 250 V in the course of the extraction process, acidic, and basic drugs were extracted from a 3.0 mL aqueous sample solution into 25 μL acceptor solutions. The pH values of the donor and acceptor solutions in the cathodic cell were 5.0 and 1.5, respectively, the corresponding values in the anodic cell were, however, 8.0 and 12.5, respectively. The rates of recovery obtained within 20 min of extraction time at a stirring rate of 750 rpm ranged from 45 to 54%. With correlation coefficients ranging from 0.990 to 0.996, the proposed EME technique provided good linearity over a concentration range of 20-1000 ng/mL. The LOD for all drugs was found to be 6.7 ng/mL, while reproducibility ranged from 7 to 12% (n = 5). Finally, applying the proposed method to determine and quantify the drugs in urine and wastewater samples, satisfactory results were achieved. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

12 CFR 900.1 - Basic terms relating to the Finance Board, the Bank System and related entities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Basic terms relating to the Finance Board, the Bank System and related entities. 900.1 Section 900.1 Banks and Banking FEDERAL HOUSING FINANCE BOARD GENERAL DEFINITIONS GENERAL DEFINITIONS APPLYING TO ALL FINANCE BOARD REGULATIONS § 900.1 Basic terms relating to the Finance Board, the Bank Syste...

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

Pierce, Eric M.; Freshley, Mark D.; Hubbard, Susan S.

In this report, we start by examining previous efforts at linking science and DOE EM research with cleanup activities. Many of these efforts were initiated by creating science and technology roadmaps. A recurring feature of successfully implementing these roadmaps into EM applied research efforts and successful cleanup is the focus on integration. Such integration takes many forms, ranging from combining information generated by various scientific disciplines, to providing technical expertise to facilitate successful application of novel technology, to bringing the resources and creativity of many to address the common goal of moving EM cleanup forward. Successful projects identify and focusmore » research efforts on addressing the problems and challenges that are causing “failure” in actual cleanup activities. In this way, basic and applied science resources are used strategically to address the particular unknowns that are barriers to cleanup. The brief descriptions of the Office of Science basic (Environmental Remediation Science Program [ERSP]) and EM’s applied (Groundwater and Soil Remediation Program) research programs in subsurface science provide context to the five “crosscutting” themes that have been developed in this strategic planning effort. To address these challenges and opportunities, a tiered systematic approach is proposed that leverages basic science investments with new applied research investments from the DOE Office of Engineering and Technology within the framework of the identified basic science and applied research crosscutting themes. These themes are evident in the initial portfolio of initiatives in the EM groundwater and soil cleanup multi-year program plan. As stated in a companion document for tank waste processing (Bredt et al. 2008), in addition to achieving its mission, DOE EM is experiencing a fundamental shift in philosophy from driving to closure to enabling the long-term needs of DOE and the nation.« less

34 CFR 1100.5 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the adult literacy, family literacy, adult education, or related field. Relevant experience includes... or education or education related fields: basic and applied research, planning, surveys, assessments... 34 Education 4 2012-07-01 2012-07-01 false What definitions apply? 1100.5 Section 1100.5 Education...

34 CFR 403.62 - What administrative provisions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION... for the basic programs may consider granting academic credit for vocational education courses that... 34 Education 3 2011-07-01 2011-07-01 false What administrative provisions apply? 403.62 Section...

34 CFR 403.62 - What administrative provisions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION... for the basic programs may consider granting academic credit for vocational education courses that... 34 Education 3 2014-07-01 2014-07-01 false What administrative provisions apply? 403.62 Section...

34 CFR 403.62 - What administrative provisions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION... for the basic programs may consider granting academic credit for vocational education courses that... 34 Education 3 2013-07-01 2013-07-01 false What administrative provisions apply? 403.62 Section...

34 CFR 1100.5 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the adult literacy, family literacy, adult education, or related field. Relevant experience includes... or education or education related fields: basic and applied research, planning, surveys, assessments... 34 Education 4 2014-07-01 2014-07-01 false What definitions apply? 1100.5 Section 1100.5 Education...

34 CFR 1100.5 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the adult literacy, family literacy, adult education, or related field. Relevant experience includes... or education or education related fields: basic and applied research, planning, surveys, assessments... 34 Education 4 2013-07-01 2013-07-01 false What definitions apply? 1100.5 Section 1100.5 Education...

34 CFR 403.62 - What administrative provisions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION... for the basic programs may consider granting academic credit for vocational education courses that... 34 Education 3 2012-07-01 2012-07-01 false What administrative provisions apply? 403.62 Section...

Focus on Basics, 1997.

ERIC Educational Resources Information Center

Focus on Basics, 1997

1997-01-01

Together, these four newsletters contain 36 articles devoted to adult literacy research and practice and the relationship between them. The following articles are included: "A Productive Partnership" (Richard J. Murnane, Bob Bickerton); "Welcome to 'Focus on Basics'" (Barbara Garner); "Applying Research on the Last Frontier" (Karen Backlund, Kathy…

The Basic Economics of CD-ROM Pricing.

ERIC Educational Resources Information Center

Erkkila, John E.

1991-01-01

This explanation of how the basic economic model of pricing applies to the CD-ROM industry considers the supply and demand sides of the market and compares three distinct pricing strategies: (1) pricing to maximize profits; (2) average cost pricing; and (3) marginal cost pricing. (EAM)

Basic Math I.

ERIC Educational Resources Information Center

Mercer County Community Coll., Trenton, NJ.

This document offers instructional materials for a 60-hour course on basic math operations involving decimals, fractions, and proportions as applied in the workplace. The course, part of a workplace literacy project developed by Mercer County Community College (New Jersey) and its partners, contains the following: course outline; 17 lesson…

Immunology update: topics in basic and clinically applied reproductive immunology.

PubMed

Hunt, J S

1996-05-01

A postgraduate course covering basic and clinical reproductive immunology was held in Philadelphia, PA, U.S.A., on March 19, 1996, in conjunction with the annual meeting of the Society for Gynecological Investigation. The course was organized and chaired by Joseph A. Hill.

Quantitative approach for defining basic color terms and color category best exemplars.

PubMed

Fider, Nicole; Narens, Louis; Jameson, Kimberly A; Komarova, Natalia L

2017-08-01

A new method is presented that identifies basic color terms (BCTs) from color-naming data. A function is defined that measures how well a term is understood by a communicating population. BCTs are then separated from other color terms by a threshold value applied to this function. A new mathematical algorithm is proposed and analyzed for determining the best exemplar associated with each BCT. Using data provided by the World Color Survey, comparisons are made between the paper's methods and those from other studies. These comparisons show that the paper's new definition of "basicness" mostly agrees with the typical definition found in the color categorization literature, which was originally due to Kay and colleagues. The new definition, unlike the typical one, has the advantage of not relying on syntactic or semantic features of languages or color lexicons. This permits the methodology developed to be generalizable and applied to other category domains for which a construct of "basicness" could have an important role.

Technology | Frederick National Laboratory for Cancer Research

Cancer.gov

The Frederick National Laboratory develops and applies advanced, next-generation technologies to solve basic and applied problems in the biomedical sciences, and serves as a national resource of shared high-tech facilities.

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

PubMed Central

Di Matteo, A; Franceschini, M; Paiardini, A; Grottesi, A; Chiarella, S; Rocchio, S; Di Natale, C; Marasco, D; Vitagliano, L; Travaglini-Allocatelli, C; Federici, L

2017-01-01

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment. PMID:28920929

Contact angle determination procedure and detection of an invisible surface film

NASA Technical Reports Server (NTRS)

Meyer, G.; Grat, R.

1990-01-01

The contact angle value, i.e., the tangent angle of liquid resting on a planar solid surface, is a basic parameter which can be applied to a wide range of applications. The goal is to provide a basic understanding of the contact angle measurement technique and to present a simple illustration that can be applied as a quality control method; namely, detection of a surface contaminant which exists on a surface that appears clean to the unaided eye. The equipment and experimental procedures are detailed.

76 FR 7526 - Major System Acquisition; Earned Value Management

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-10

... for engineering support services, steady state operations, basic and applied research, and routine... the requirements in the NASA NPR to apply EVM principles at the program/project level; nor is it...

Disability retirement

NASA Technical Reports Server (NTRS)

Eck, R. L.

1975-01-01

Eligibility for disability retirement is discussed. General guidelines and a few standards are given. Usually the same basic medical principles apply to the evaluation of claims for disability retirement as apply to determining medical suitability for initial employment.

5 CFR 531.207 - Applying annual pay adjustments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Applying annual pay adjustments. 531.207 Section 531.207 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Determining Rate of Basic Pay General Provisions § 531.207 Applying annual...

An Endocrine Pharmacology Course for the Clinically-Oriented Pharmacy Curriculum

ERIC Educational Resources Information Center

Rahwan, Ralf G.

1976-01-01

In view of trends in clinical pharmacy education, the role of the traditional basic sciences has to be reassessed. An endocrine pharmacology course comprised of 49 clock-hours and open for professional undergraduate and graduate credit is described that blends basic and applied pharmacology. (LBH)

Is Respiration-Induced Variation in the Photoplethysmogram Associated with Major Hypovolemia in Patients with Acute Traumatic Injuries?

DTIC Science & Technology

2010-11-01

hypovolemia in the prehospital environment. Photoplethysmogram waveforms and basic vital signs were recorded in trauma patients during prehospital...transport. Retrospectively, we used automated algorithms to select patient records with all five basic vital signs and 45 s or longer continuous, clean PPG... basic vital signs by applying multivariate regression. In 344 patients, RIWV max-min yielded areas under the ROC curves (AUCs) not significantly better

Effectiveness of Active Learning Strategy in Improving the Acoustic Awareness Skills and Understanding What Is Heard by the Basic Stage Students in Jordan

ERIC Educational Resources Information Center

Al-Odwan, Yaser

2016-01-01

This research aims to get acquainted with the effectiveness of the active learning strategy in improving the acoustic awareness skills and understanding what is heard by the basic stage students in Jordan by answering the two following questions: This research has been applied to a sample of 60 students from the basic third grade in Al-Ahnaf Ben…

Applied behavior analysis: New directions from the laboratory

PubMed Central

Epling, W. Frank; Pierce, W. David

1983-01-01

Applied behavior analysis began when laboratory based principles were extended to humans inorder to change socially significant behavior. Recent laboratory findings may have applied relevance; however, the majority of basic researchers have not clearly communicated the practical implications of their work. The present paper samples some of the new findings and attempts to demonstrate their applied importance. Schedule-induced behavior which occurs as a by-product of contingencies of reinforcement is discussed. Possible difficulties in treatment and management of induced behaviors are considered. Next, the correlation-based law of effect and the implications of relative reinforcement are explored in terms of applied examples. Relative rate of reinforcement is then extended to the literature dealing with concurrent operants. Concurrent operant models may describe human behavior of applied importance, and several techniques for modification of problem behavior are suggested. As a final concern, the paper discusses several new paradigms. While the practical importance of these models is not clear at the moment, it may be that new practical advantages will soon arise. Thus, it is argued that basic research continues to be of theoretical and practical importance to applied behavior analysis. PMID:22478574

Research in progress in applied mathematics, numerical analysis, and computer science

NASA Technical Reports Server (NTRS)

1990-01-01

Research conducted at the Institute in Science and Engineering in applied mathematics, numerical analysis, and computer science is summarized. The Institute conducts unclassified basic research in applied mathematics in order to extend and improve problem solving capabilities in science and engineering, particularly in aeronautics and space.

Community College Students and Applied Research. Professional File. Number 30

ERIC Educational Resources Information Center

Zuniga, Sabrina Faust

2009-01-01

Student participation in applied research as a form of experiential learning in community colleges is relatively new. Ontario Colleges today participate at different levels with different numbers of projects and faculty involved. A few colleges in Ontario are more established in doing applied research including having basic infrastructure for…

48 CFR 334.201 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... & Validation services), steady state operations, basic and applied research, and routine services (e.g... of the cognizant HCA. (b) EVM is not required, but may be applied with prior written approval of the...(s) under FAR Part 12. (c) When full EVM is required on a prime contract, it applies to subcontracts...

Temporal discounting: basic research and the analysis of socially important behavior.

PubMed Central

Critchfield, T S; Kollins, S H

2001-01-01

Recent basic research on human temporal discounting is reviewed to illustrate procedures, summarize key findings, and draw parallels with both nonhuman animal research and conceptual writings on self-control. Lessons derived from this research are then applied to the challenge of analyzing socially important behaviors such as drug abuse, eating and exercise, and impulsiveness associated with attention deficit hyperactivity disorder. Attending to the broader temporal context in which behavior occurs may aid in the analysis of socially important behavior. Applying this perspective to the study of behavior in natural environments also highlights the importance of combining methodological flexibility with conceptual rigor to promote the extension of applied behavior analysis to a broader array of socially important behaviors. PMID:11317983

ECON 12: Teacher's Materials. Units I and II.

ERIC Educational Resources Information Center

Wiggins, Suzanne

The objectives of this experimental 12th grade economics course begin with an understanding that "economic analysis applies a set of basic concepts and their interrelationships to problems (involving) economic scarcity." Fifteen basic concepts are to be learned (e. g., want, markets, money, etc.) as well as the definition and vocabulary…

Basic Drafting: Book One.

ERIC Educational Resources Information Center

Davis, Ronald; And Others

The first of a two-book course in drafting, this manual consists of 13 topics in the following units: introduction to drafting, general safety, basic tools and lines, major equipment, applying for a job, media, lettering, reproduction, drawing sheet layout, architect's scale usage, civil engineer's scale usage, mechanical engineer's scale usage,…

Senior Computational Scientist | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP),

Fractional vector calculus for fractional advection dispersion

NASA Astrophysics Data System (ADS)

Meerschaert, Mark M.; Mortensen, Jeff; Wheatcraft, Stephen W.

2006-07-01

We develop the basic tools of fractional vector calculus including a fractional derivative version of the gradient, divergence, and curl, and a fractional divergence theorem and Stokes theorem. These basic tools are then applied to provide a physical explanation for the fractional advection-dispersion equation for flow in heterogeneous porous media.

Basic Applied Mathematics Part 1.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

This guide, published by the New York City Board of Education, presents 62 lesson plans in basic mathematics for tenth grade students. Lesson plans and performance objectives focus on the following areas: (1) fundamental operations with signed numbers; (2) linear, weight and temperature measurements; (3) fractions, decimals and percents; (4)…

ON THE NATURE OF SPEECH SCIENCE.

ERIC Educational Resources Information Center

PETERSON, GORDON E.

IN THIS ARTICLE THE NATURE OF THE DISCIPLINE OF SPEECH SCIENCE IS CONSIDERED AND THE VARIOUS BASIC AND APPLIED AREAS OF THE DISCIPLINE ARE DISCUSSED. THE BASIC AREAS ENCOMPASS THE VARIOUS PROCESSES OF THE PHYSIOLOGY OF SPEECH PRODUCTION, THE ACOUSTICAL CHARACTERISTICS OF SPEECH, INCLUDING THE SPEECH WAVE TYPES AND THE INFORMATION-BEARING ACOUSTIC…

Basic Electricity. Training Module 3.325.1.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module package prepared in objective form for use by an instructor familiar with the basic concepts of electricity as applied to water and wastewater treatment. Included are objectives, instructor guides, student handouts, and transparency masters. This module considers definition of terms, voltage, current…

Secretary | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research programs in basic or applied molecular biology, immunology, retrovirology, cancer biology, or human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick national Laboratory for Cancer Research (FNLCR). The BSP Office provides

La Gramatica Ingles: Libro de Trabajo (English Grammar: Workbook).

ERIC Educational Resources Information Center

Rogers, Paul

This student workbook is designed for native Spanish-speaking learners of English as a second language, and presents instruction in basic English grammatical constructions and usage, as well as some vocabulary development. Lessons include basic descriptions of the constructions and rules in applying them, and a brief exercise reinforcing the…

JSC interactive basic accounting system

NASA Technical Reports Server (NTRS)

Spitzer, J. F.

1978-01-01

Design concepts for an interactive basic accounting system (IBAS) are considered in terms of selecting the design option which provides the best response at the lowest cost. Modeling the IBAS workload and applying this workload to a U1108 EXEC 8 based system using both a simulation model and the real system is discussed.

Inventory of Data Sources in Science and Technology. A Preliminary Survey.

ERIC Educational Resources Information Center

International Council of Scientific Unions, Paris (France).

Provided in this inventory are sources of numerical or factual data in selected fields of basic science and applied science/technology. The objective of the inventory is to provide organizations and individuals (scientists, engineers, and information specialists), particularly those in developing countries, with basic data sources relevant to…

34 CFR 403.60 - What are the basic programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 3 2012-07-01 2012-07-01 false What are the basic programs? 403.60 Section 403.60... ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What... Vocational Education Programs. (f) Postsecondary and Adult Vocational Education Programs. (Authority: 20 U.S...

34 CFR 403.60 - What are the basic programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 3 2013-07-01 2013-07-01 false What are the basic programs? 403.60 Section 403.60... ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What... Vocational Education Programs. (f) Postsecondary and Adult Vocational Education Programs. (Authority: 20 U.S...

34 CFR 403.60 - What are the basic programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What are the basic programs? 403.60 Section 403.60... ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What... Vocational Education Programs. (f) Postsecondary and Adult Vocational Education Programs. (Authority: 20 U.S...

34 CFR 403.60 - What are the basic programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 3 2014-07-01 2014-07-01 false What are the basic programs? 403.60 Section 403.60... ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What... Vocational Education Programs. (f) Postsecondary and Adult Vocational Education Programs. (Authority: 20 U.S...

A snapshot of translational research funded by the National Institutes of Health (NIH): A case study using behavioral and social science research awards and Clinical and Translational Science Awards funded publications.

PubMed

Han, Xueying; Williams, Sharon R; Zuckerman, Brian L

2018-01-01

The translation of biomedical research from basic knowledge to application has been a priority at the National Institute of Health (NIH) for many years. Tracking the progress of scientific research and knowledge through the translational process is difficult due to variation in the definition of translational research as well as the identification of benchmarks for the spread and application of biomedical research; quantitatively tracking this process is even more difficult. Using a simple and reproducible method to assess whether publications are translational, we examined NIH R01 behavioral and social science research (BSSR) awards funded between 2008 and 2014 to determine whether there are differences in the percent of translational research publications produced by basic and applied research awards. We also assessed the percent of translational research publications produced by the Clinical and Translational Science Awards (CTSA) program to evaluate whether targeted translational research awards result in increased translational research. We found that 3.9% of publications produced by basic research awards were translational; that the percent of translational research publications produced by applied research awards is approximately double that of basic research awards (7.4%); and that targeted translational research awards from the CTSA program produced the highest percentage of translational research publications (13.4%). In addition, we assessed differences in time to first publication, time to first citation, and publication quality by award type (basic vs. applied), and whether an award (or publication) is translational.

A snapshot of translational research funded by the National Institutes of Health (NIH): A case study using behavioral and social science research awards and Clinical and Translational Science Awards funded publications

PubMed Central

Williams, Sharon R.; Zuckerman, Brian L.

2018-01-01

The translation of biomedical research from basic knowledge to application has been a priority at the National Institute of Health (NIH) for many years. Tracking the progress of scientific research and knowledge through the translational process is difficult due to variation in the definition of translational research as well as the identification of benchmarks for the spread and application of biomedical research; quantitatively tracking this process is even more difficult. Using a simple and reproducible method to assess whether publications are translational, we examined NIH R01 behavioral and social science research (BSSR) awards funded between 2008 and 2014 to determine whether there are differences in the percent of translational research publications produced by basic and applied research awards. We also assessed the percent of translational research publications produced by the Clinical and Translational Science Awards (CTSA) program to evaluate whether targeted translational research awards result in increased translational research. We found that 3.9% of publications produced by basic research awards were translational; that the percent of translational research publications produced by applied research awards is approximately double that of basic research awards (7.4%); and that targeted translational research awards from the CTSA program produced the highest percentage of translational research publications (13.4%). In addition, we assessed differences in time to first publication, time to first citation, and publication quality by award type (basic vs. applied), and whether an award (or publication) is translational. PMID:29742129

Basic Sciences Fertilizing Clinical Microbiology and Infection Management

PubMed Central

2017-01-01

Abstract Basic sciences constitute the most abundant sources of creativity and innovation, as they are based on the passion of knowing. Basic knowledge, in close and fertile contact with medical and public health needs, produces distinct advancements in applied sciences. Basic sciences play the role of stem cells, providing material and semantics to construct differentiated tissues and organisms and enabling specialized functions and applications. However, eventually processes of “practice deconstruction” might reveal basic questions, as in de-differentiation of tissue cells. Basic sciences, microbiology, infectious diseases, and public health constitute an epistemological gradient that should also be an investigational continuum. The coexistence of all these interests and their cross-fertilization should be favored by interdisciplinary, integrative research organizations working simultaneously in the analytical and synthetic dimensions of scientific knowledge. PMID:28859345

The national labs and their future

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

Crease, R.P.

National laboratories of the USA, born with the atomic age and raised to prominence by the need for scientific superiority during the long Cold War, are facing the most critical challenge: how best to support the nation's current need to improve its international competitiveness through superior technology The charge that the national laboratories are [open quotes]Cold War relics[close quotes] that have outlived their usefulness is based on a misunderstanding of their mission, says Robert P. Crease, historian for Brookhaven National laboratory. Three of the labs-Los Alamos, Sandia, and Lawrence Livermore- are weapons laboratories and their missions must change. Oak Ridge,more » Argonne, and Brookhaven laboratories are multipurpose: basic research facilities with a continuing role in the world of science The national laboratory system traces its origins to the Manhattan Project. Over the next half-century, America's national labs grew into part of the most effective scientific establishment in the world, a much-copied model for management of large-scale scientific programs. In the early years, each lab defined a niche in the complex world of reactors, accelerators, and high-energy proton and electron physics. In the 1970s, several labs worked on basic energy sciences to help solve a national energy crisis. Today, the labs are pressured to do more applied research-research to transfer to the private sector and will have to respond by devising more effective ways of coordinating basic and applied research. But, Crease warns, [open quotes]It also will be essential that any commitment to applied research not take place at the cost of reducing the wellspring of basic research from which so much applied research flows. [open quotes]Making a solid and persuasive case for the independent value of basic research, and for their own role in that enterprise, may be the most important task facing the laboratories in their next half-century,[close quotes].« less

34 CFR 403.102 - What other requirements apply to the Program for Criminal Offenders?

Code of Federal Regulations, 2010 CFR

2010-07-01

... APPLIED TECHNOLOGY EDUCATION PROGRAM What Kinds of Activities Does the Secretary Assist Under the Basic... Criminal Offenders? Each State corrections educational agency designated under § 403.100(a) shall meet the...

Thermal evaluation of advanced solar dynamic heat receiver performance

NASA Technical Reports Server (NTRS)

Crane, Roger A.

1989-01-01

The thermal performance of a variety of concepts for thermal energy storage as applied to solar dynamic applications is discussed. It is recognized that designs providing large thermal gradients or large temperature swings during orbit are susceptible to early mechanical failure. Concepts incorporating heat pipe technology may encounter operational limitations over sufficiently large ranges. By reviewing the thermal performance of basic designs, the relative merits of the basic concepts are compared. In addition the effect of thermal enhancement and metal utilization as applied to each design provides a partial characterization of the performance improvements to be achieved by developing these technologies.

Basic principles of Hasse diagram technique in chemistry.

PubMed

Brüggemann, Rainer; Voigt, Kristina

2008-11-01

Principles of partial order applied to ranking are explained. The Hasse diagram technique (HDT) is the application of partial order theory based on a data matrix. In this paper, HDT is introduced in a stepwise procedure, and some elementary theorems are exemplified. The focus is to show how the multivariate character of a data matrix is realized by HDT and in which cases one should apply other mathematical or statistical methods. Many simple examples illustrate the basic theoretical ideas. Finally, it is shown that HDT is a useful alternative for the evaluation of antifouling agents, which was originally performed by amoeba diagrams.

34 CFR 403.102 - What other requirements apply to the Program for Criminal Offenders?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What Kinds of Activities Does the Secretary Assist Under the Basic... 34 Education 3 2011-07-01 2011-07-01 false What other requirements apply to the Program for...

34 CFR 403.102 - What other requirements apply to the Program for Criminal Offenders?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What Kinds of Activities Does the Secretary Assist Under the Basic... 34 Education 3 2014-07-01 2014-07-01 false What other requirements apply to the Program for...

34 CFR 403.102 - What other requirements apply to the Program for Criminal Offenders?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What Kinds of Activities Does the Secretary Assist Under the Basic... 34 Education 3 2013-07-01 2013-07-01 false What other requirements apply to the Program for...

34 CFR 403.102 - What other requirements apply to the Program for Criminal Offenders?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAM What Kinds of Activities Does the Secretary Assist Under the Basic... 34 Education 3 2012-07-01 2012-07-01 false What other requirements apply to the Program for...

Staircase and Fractional Part Functions

ERIC Educational Resources Information Center

Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel

2016-01-01

The staircase and fractional part functions are basic examples of real functions. They can be applied in several parts of mathematics, such as analysis, number theory, formulas for primes, and so on; in computer programming, the floor and ceiling functions are provided by a significant number of programming languages--they have some basic uses in…

University Research: The Role of Federal Funding

ERIC Educational Resources Information Center

Association of American Universities, 2011

2011-01-01

University research is a vital building block of the nation's research and development (R&D) enterprise. While U.S. universities perform just 13 percent of total national R&D, they perform 31 percent of the nation's total research--basic and applied--and 56 percent of the nation's basic research. Because there is broad consensus that…

Proxy Measurement of Adult Basic Skills: Lessons from Canada.

ERIC Educational Resources Information Center

Murray, T. Scott

"Proxy" measures have been developed and applied that extend the usefulness of direct assessments of adult basic skills. Three categories of users of data on adult literacy are as follows: (1) government authorities who need objective data to inform the decision-making process; (2) program delivery institutions who require an assessment…

20 CFR 901.13 - Eligibility for enrollment of individuals applying for enrollment on or after January 1, 1976.

Code of Federal Regulations, 2011 CFR

2011-04-01

... actuarial mathematics and methodology by one of the following: (1) Joint Board basic examination. Successful... basic actuarial mathematics and methodology including compound interest, principles of life... major area of concentration was actuarial mathematics, or (ii) Which included at least as many semester...

Mathematics: A Practical View. Volume I, Teacher Edition. Applied Basic Curriculum Series.

ERIC Educational Resources Information Center

Evaluation, Dissemination and Assessment Center, Dallas.

The activities in this volume of practical mathematics are intended for the intermediate grades. The manual contains three components which can be structured in different combinations according to different student needs. Built around a review of selected objectives in the mathematics basic curriculum, the material is intended to stimulate…

Integration of Basic Skills into Social Studies Content.

ERIC Educational Resources Information Center

Lunstrum, John P.; Irvin, Judith L.

1981-01-01

A basic skills model is presented which stresses the skills of writing, reading, study, and research for elementary school pupils. The model focuses on lesson background, the purpose of the reading, independent reading, follow-up discussion, developing related skills, and extending and applying ideas. A lesson about the 1910 British expedition to…

Counterfactual Reasoning: Developing a Sense of "Nearest Possible World"

ERIC Educational Resources Information Center

Rafetseder, Eva; Cristi-Vargas, Renate; Perner, Josef

2010-01-01

This study investigated at what point in development 3- to 6-year-old children begin to demonstrate counterfactual reasoning by controlling for fortuitously correct answers that result from basic conditional reasoning. "Basic conditional reasoning" occurs when one applies typical regularities (such as "If 'whenever' it doesn't rain the street is…

Effluent-Monitoring Procedures: Basic Laboratory Skills. Student Reference Manual.

ERIC Educational Resources Information Center

Engel, William T.; And Others

This is one of several short-term courses developed to assist in the training of waste water treatment plant operational personnel in the tests, measurements, and report preparation required for compliance with their NPDES Permits. This Student Reference Manual provides a review of basic mathematics as it applies to the chemical laboratory. The…

Using Data Mining to Teach Applied Statistics and Correlation

ERIC Educational Resources Information Center

Hartnett, Jessica L.

2016-01-01

This article describes two class activities that introduce the concept of data mining and very basic data mining analyses. Assessment data suggest that students learned some of the conceptual basics of data mining, understood some of the ethical concerns related to the practice, and were able to perform correlations via the Statistical Package for…

Learning Basic English in Overcrowded Classes for True Beginners

ERIC Educational Resources Information Center

Santana, Isaias

2016-01-01

The higher educational institution where this study took place is located in the Dominican Republic. The purpose of this study was to provide insights to the effectiveness and impact of the instructional process applied in a Basic English class under overcrowding conditions, implementing an in depth interview to the faculty members and an…

78 FR 39337 - Importer of Controlled Substances; Notice of Application; Akorn, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

...), a basic class of controlled substance listed in schedule II. The company plans to import Remifentanil in bulk for use in dosage- form manufacturing. Any bulk manufacturer who is presently, or is applying to be, registered with DEA to manufacture such basic class of controlled substance listed in...

The Boyer Commission Report on Evaluation of Teaching: Implications in the Basic Course.

ERIC Educational Resources Information Center

Hugenberg, Lawrence W.

In his book "Scholarship Assessed" and in a speech summarizing the book, Ernest Boyer, President of the Carnegie Foundation for the Advancement of Teaching, considers faculty evaluation issues. Applying Boyer's ideas to the basic communication course allows the integration of new insights and perspectives into the daily operations of the…

A Concept Transformation Learning Model for Architectural Design Learning Process

ERIC Educational Resources Information Center

Wu, Yun-Wu; Weng, Kuo-Hua; Young, Li-Ming

2016-01-01

Generally, in the foundation course of architectural design, much emphasis is placed on teaching of the basic design skills without focusing on teaching students to apply the basic design concepts in their architectural designs or promoting students' own creativity. Therefore, this study aims to propose a concept transformation learning model to…

Getting Back to Basics (& Acidics)

ERIC Educational Resources Information Center

Rhodes, Sam

2006-01-01

This article describes a few novel acid-base experiments intended to introduce students to the basic concepts of acid-base chemistry and provide practical examples that apply directly to the study of biology and the human body. Important concepts such as the reaction between carbon dioxide and water, buffers and protein denaturation, are covered.…

Appliance Services. Basic Course. Career Education.

ERIC Educational Resources Information Center

Killough, Joseph

Several intermediate performance objectives and corresponding criterion measures are listed for each of 25 terminal objectives for a basic appliance repair course. The materials were developed for a 36-week course (2 hours daily) designed to enable the student to be well-grounded in the fundamentals of electricity as well as applied electricity.…

Basic Considerations in the Combustion of Hydrocarbon Fuels with Air

NASA Technical Reports Server (NTRS)

Barnett, Henry C; Hibbard, Robert R

1957-01-01

Basic combustion research is collected, collated, and interpreted as it applies to flight propulsion. The following fundamental processes are treated in separate chapters: atomization and evaporation of liquid fuels, flow and mixing processes in combustion chambers, ignition and flammability of hydrocarbon fuels, laminar flame propagation, turbulent flames, flame stabilization, diffusion flames, oscillations in combustors, and smoke and coke formation in the combustion of hydrocarbon-air mixtures. Theoretical background, basic experimental data, and practical significance to flight propulsion are presented.

The Brown Superfund Basic Research Program: A Multistakeholder Partnership Addresses Real-World Problems in Contaminated Communities

PubMed Central

Senier, Laura; Hudson, Benjamin; Fort, Sarah; Hoover, Elizabeth; Tillson, Rebecca; Brown, Phil

2008-01-01

The NIEHS funds several basic and applied research programs, many of which also require research translation or outreach. This paper reports on a project by the Brown University Superfund Basic Research Program (SBRP), in which outreach and research translation teams collaborated with state regulatory agency personnel and community activists on a legislative initiative to mitigate the financial impacts of living in a contaminated community. The Environmentally Compromised Home Ownership (ECHO) program makes home equity loans of up to $25,000 available to qualified applicants. This collaboration provides a case study in community engagement and demonstrates how research translation and outreach activities that are clearly differentiated yet well integrated can improve a suite of basic and applied research. Although engaging diverse constituencies can be difficult, community-engaged translation and outreach have the potential to make research findings more useful to communities, address some of the social impacts of contamination, and empower stakeholders to pursue their individual and collectively-held goals for remediation. The NIEHS has recently renewed its commitment to community-engaged research and advocacy, making this an optimal time to reflect on how basic research programs that engage stakeholders through research translation and outreach can add value to the overall research enterprise. PMID:18677987

Brown Superfund Basic research Program: a multistakeholder partnership addresses real-world problems in contaminated communities.

PubMed

Senier, Laura; Hudson, Benjamin; Fort, Sarah; Hoover, Elizabeth; Tillson, Rebecca; Brown, Phil

2008-07-01

The NIEHS funds several basic and applied research programs, many of which also require research translation or outreach. This paper reports on a project by the Brown University Superfund Basic Research Program (SBRP), in which outreach and research translation teams collaborated with state regulatory agency personnel and community activists on a legislative initiative to mitigate the financial impacts of living in a contaminated community. The Environmentally Compromised Home Ownership (ECHO) program makes home equity loans of up to $25,000 available to qualified applicants. This collaboration provides a case study in community engagement and demonstrates how research translation and outreach activities that are clearly differentiated yet well-integrated can improve a suite of basic and applied research. Although engaging diverse constituencies can be difficult community-engaged translation and outreach have the potential to make research findings more useful to communities, address some of the social impacts of contamination, and empower stakeholders to pursue their individual and collectively held goals for remediation. The NIEHS has recently renewed its commitment to community-engaged research and advocacy, making this an optimal time to reflect on how basic research programs that engage stakeholders through research translation and outreach can add value to the overall research enterprise.

Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy.

PubMed

Wang, Zhi-Hui; Li, Dong-Dong; Chen, Wei-Lin; You, Qi-Dong; Guo, Xiao-Ke

2018-01-15

The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed. Copyright © 2017. Published by Elsevier Ltd.

Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells

PubMed Central

Vu, Ly P.; Prieto, Camila; Amin, Elianna M.; Chhangawala, Sagar; Krivtsov, Andrei; Calvo-Vidal, M. Nieves; Chou, Timothy; Chow, Arthur; Minuesa, Gerard; Park, Sun Mi; Barlowe, Trevor S.; Taggart, James; Tivnan, Patrick; Deering, Raquel P.; Chu, Lisa P; Kwon, Jeong-Ah; Meydan, Cem; Perales-Paton, Javier; Arshi, Arora; Gönen, Mithat; Famulare, Christopher; Patel, Minal; Paietta, Elisabeth; Tallman, Martin S.; Lu, Yuheng; Glass, Jacob; Garret-Bakelman, Francine; Melnick, Ari; Levine, Ross; Al-Shahrour, Fatima; Järås, Marcus; Hacohen, Nir; Hwang, Alexia; Garippa, Ralph; Lengner, Christopher J.; Armstrong, Scott A; Cerchietti, Leandro; Cowley, Glenn S; Root, David; Doench, John; Leslie, Christina; Ebert, Benjamin L; Kharas, Michael G.

2017-01-01

The identity of the RNA binding proteins (RBPs) that govern cancer stem cell remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomics analysis of the MSI2 interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia and SYNCRIP was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell gene associated program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. We validated SYNCRIP as a novel RBP that controls the myeloid leukemia stem cell program and propose that targeting these functional complexes might provide a novel therapeutic strategy in leukemia. PMID:28436985

Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients.

PubMed

Bergallo, Massimiliano; Montanari, Paola; Mareschi, Katia; Merlino, Chiara; Berger, Massimo; Bini, Ilaria; Daprà, Valentina; Galliano, Ilaria; Fagioli, Franca

2017-12-01

The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression. Our findings show that HERV-K expression was significantly higher in leukaemia patients when compared to healthy donors of a similar median age. We observed a significantly high expression of HERV-K in acute lymphoblastic leukemia (ALL) patients. In this study, we also found a relative overexpression of the endogenous retrovirus HERV-K in BM cells from the majority of leukemia samples analyzed, in particular in ALL. This overexpression might be related to lymphatic leukemogenesis and it warrants further investigations.

The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling.

PubMed

Izutsu, K; Kurokawa, M; Imai, Y; Maki, K; Mitani, K; Hirai, H

2001-05-01

Evi-1 is a zinc finger nuclear protein whose inappropriate expression leads to leukemic transformation of hematopoietic cells in mice and humans. This was previously shown to block the antiproliferative effect of transforming growth factor beta (TGF-beta). Evi-1 represses TGF-beta signaling by direct interaction with Smad3 through its first zinc finger motif. Here, it is demonstrated that Evi-1 represses Smad-induced transcription by recruiting C-terminal binding protein (CtBP) as a corepressor. Evi-1 associates with CtBP1 through one of the consensus binding motifs, and this association is required for efficient inhibition of TGF-beta signaling. A specific inhibitor for histone deacetylase (HDAc) alleviates Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved in the transcriptional repression by Evi-1. This identifies a novel function of Evi-1 as a member of corepressor complexes and suggests that aberrant recruitment of corepressors is one of the mechanisms for Evi-1-induced leukemogenesis.

Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia.

PubMed

Grembecka, Jolanta; He, Shihan; Shi, Aibin; Purohit, Trupta; Muntean, Andrew G; Sorenson, Roderick J; Showalter, Hollis D; Murai, Marcelo J; Belcher, Amalia M; Hartley, Thomas; Hess, Jay L; Cierpicki, Tomasz

2012-01-29

Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are to our knowledge the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities. These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. They also selectively block proliferation and induce both apoptosis and differentiation of leukemia cells harboring MLL translocations. Identification of these compounds provides a new tool for better understanding MLL-mediated leukemogenesis and represents a new approach for studying the role of menin as an oncogenic cofactor of MLL fusion proteins. Our findings also highlight a new therapeutic strategy for aggressive leukemias with MLL rearrangements.

Evolution of AF6-RAS association and its implications in mixed-lineage leukemia

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

Smith, Matthew J.; Ottoni, Elizabeth; Ishiyama, Noboru

Elucidation of activation mechanisms governing protein fusions is essential for therapeutic development. MLL undergoes rearrangement with numerous partners, including a recurrent translocation fusing the epigenetic regulator to a cytoplasmic RAS effector, AF6/afadin. We show here that AF6 employs a non-canonical, evolutionarily conserved α-helix to bind RAS, unique to AF6 and the classical RASSF effectors. Further, all patients with MLL-AF6 translocations express fusion proteins missing only this helix from AF6, resulting in exposure of hydrophobic residues that induce dimerization. We provide evidence that oligomerization is the dominant mechanism driving oncogenesis from rare MLL translocation partners and employ our mechanistic understanding ofmore » MLL-AF6 to examine how dimers induce leukemia. Proteomic data resolve association of dimerized MLL with gene expression modulators, and inhibiting dimerization disrupts formation of these complexes while completely abrogating leukemogenesis in mice. Oncogenic gene translocations are thus selected under pressure from protein structure/function, underscoring the complex nature of chromosomal rearrangements.« less

Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

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

Wang, Jiying; Rao, Qing, E-mail: raoqing@gmail.com; Wang, Min

2009-09-04

Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation,more » and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.« less

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.

PubMed

Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R

2016-04-19

The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

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

Grebien, Florian; Hantschel, Oliver; Wojcik, John

2012-10-25

Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of themore » SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention.« less

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility.

PubMed

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I; Hantschel, Oliver

2014-11-17

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.

PubMed

Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M; Gish, Gerald D; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio

2011-10-14

Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention. Copyright © 2011 Elsevier Inc. All rights reserved.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

NASA Astrophysics Data System (ADS)

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

2014-11-01

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

PubMed Central

Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M.; Gish, Gerald D.; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio

2011-01-01

Summary Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention. PaperFlick PMID:22000011

HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape

PubMed Central

Conte, Mariarosaria; Dell'Aversana, Carmela; Benedetti, Rosaria; Petraglia, Francesca; Carissimo, Annamaria; Petrizzi, Valeria Belsito; D'Arco, Alfonso Maria; Abbondanza, Ciro; Nebbioso, Angela; Altucci, Lucia

2015-01-01

Histone deacetylase 2 (HDAC2) is overexpressed or mutated in several disorders such as hematological cancers, and plays a critical role in transcriptional regulation, cell cycle progression and developmental processes. Here, we performed comparative transcriptome analyses in acute myeloid leukemia to investigate the biological implications of HDAC2 silencing versus its enzymatic inhibition using epigenetic-based drug(s). By gene expression analysis of HDAC2-silenced vs wild-type cells, we found that HDAC2 has a specific role in leukemogenesis. Gene expression profiling of U937 cell line with or without treatment of the well-known HDAC inhibitor vorinostat (SAHA) identifies and characterizes several gene clusters where inhibition of HDAC2 ‘mimics’ its silencing, as well as those where HDAC2 is selectively and exclusively regulated by HDAC2 protein expression levels. These findings may represent an important tool for better understanding the mechanisms underpinning immune regulation, particularly in the study of major histocompatibility complex class II genes. PMID:25473896

Horizontal integration of the basic sciences in the chiropractic curriculum.

PubMed

Ward, Kevin P

2010-01-01

Basic science curricula at most chiropractic colleges consist of courses (eg, general anatomy, physiology, biochemistry, etc) that are taught as stand-alone content domains. The lack of integration between basic science disciplines causes difficulties for students who need to understand how the parts function together as an integrated whole and apply this understanding to solving clinical problems. More horizontally integrated basic science curricula could be achieved by several means: integrated Part I National Board of Chiropractic Examiners questions, a broader education for future professors, an increased emphasis on integration within the current model, linked courses, and an integrated, thematic basic science curriculum. Horizontally integrating basic science curricula would require significant efforts from administrators, curriculum committees, and instructional faculty. Once in place this curriculum would promote more clinically relevant learning, improved learning outcomes, and superior vertical integration.

Horizontal Integration of the Basic Sciences in the Chiropractic Curriculum

PubMed Central

Ward, Kevin P.

2010-01-01

Basic science curricula at most chiropractic colleges consist of courses (eg, general anatomy, physiology, biochemistry, etc) that are taught as stand-alone content domains. The lack of integration between basic science disciplines causes difficulties for students who need to understand how the parts function together as an integrated whole and apply this understanding to solving clinical problems. More horizontally integrated basic science curricula could be achieved by several means: integrated Part I National Board of Chiropractic Examiners questions, a broader education for future professors, an increased emphasis on integration within the current model, linked courses, and an integrated, thematic basic science curriculum. Horizontally integrating basic science curricula would require significant efforts from administrators, curriculum committees, and instructional faculty. Once in place this curriculum would promote more clinically relevant learning, improved learning outcomes, and superior vertical integration. PMID:21048882

[International trends of applied ecology and its future development in China].

PubMed

Zhou, Qixing; Sun, Shunjiang

2002-07-01

Internationally applied ecology was born around 25-40 years ago in order to adapt and serve the needs of mitigating increasingly environmental pollution and ecological destroy in developed western countries at that time. All the times applied ecological principles thus underpin most efforts at solving increasingly deterioration of natural resources and serious eco-environmental problems as its keystone and researching kernel with the development of the subject. At the advent of the 21st century, human beings enter into the age of applied ecology. There are five international features of applied ecology, including more attention to many-sided applications, special emphasis on the intersection with engineering, strongly keeping on mutual links with basic ecology, omnidirectional adoption of new methods and new technology, and side-by-side trends of microcosmic mechanisms and macroscopical regulation. Although we must connect with international applied ecology and absorb distillates from the subject in developed western countries, development of applied ecology in China in the future, in particular, at the beginnings of the 21st century should not deviate from aiming at the solution of increasingly environmental pollution and ecological destroy that is one of the most important basic situations of the country.

PhysioNet: physiologic signals, time series and related open source software for basic, clinical, and applied research.

PubMed

Moody, George B; Mark, Roger G; Goldberger, Ary L

2011-01-01

PhysioNet provides free web access to over 50 collections of recorded physiologic signals and time series, and related open-source software, in support of basic, clinical, and applied research in medicine, physiology, public health, biomedical engineering and computing, and medical instrument design and evaluation. Its three components (PhysioBank, the archive of signals; PhysioToolkit, the software library; and PhysioNetWorks, the virtual laboratory for collaborative development of future PhysioBank data collections and PhysioToolkit software components) connect researchers and students who need physiologic signals and relevant software with researchers who have data and software to share. PhysioNet's annual open engineering challenges stimulate rapid progress on unsolved or poorly solved questions of basic or clinical interest, by focusing attention on achievable solutions that can be evaluated and compared objectively using freely available reference data.

A computational study of the discretization error in the solution of the Spencer-Lewis equation by doubling applied to the upwind finite-difference approximation

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

Nelson, P.; Seth, D.L.; Ray, A.K.

A detailed and systematic study of the nature of the discretization error associated with the upwind finite-difference method is presented. A basic model problem has been identified and based upon the results for this problem, a basic hypothesis regarding the accuracy of the computational solution of the Spencer-Lewis equation is formulated. The basic hypothesis is then tested under various systematic single complexifications of the basic model problem. The results of these tests provide the framework of the refined hypothesis presented in the concluding comments. 27 refs., 3 figs., 14 tabs.

Application of thermochemical modeling to aircraft interior polymeric materials

DOT National Transportation Integrated Search

1982-06-01

This report summarizes the results from a twelve-month study of the feasibility of applying certain basic concepts in the thermochemical modeling to aircraft cabin fire safety. The concepts developed earlier on a NASA-sponsored program were applied t...

Soldering tool heats workpieces and applies solder in one operation

NASA Technical Reports Server (NTRS)

Gudkese, V. W.

1966-01-01

Fountain-pen type soldering iron heats workpieces and applies solder to joints in densely packed electronics assemblies. The basic soldering tool is used with different-sized orifice tips, eliminating the need for an assortment of conventional soldering guns.

Applied Research on Laparoscopic Simulator in the Resident Surgical Laparoscopic Operation Technical Training.

PubMed

Fu, Shangxi; Liu, Xiao; Zhou, Li; Zhou, Meisheng; Wang, Liming

2017-08-01

The purpose of this study was to estimate the effects of surgical laparoscopic operation course on laparoscopic operation skills after the simulated training for medical students with relatively objective results via data gained before and after the practice course of laparoscopic simulator of the resident standardized trainees. Experiment 1: 20 resident standardized trainees with no experience in laparoscopic surgery were included in the inexperienced group and finished simulated cholecystectomy according to simulator videos. Simulator data was collected (total operation time, path length, average speed of instrument movement, movement efficiency, number of perforations, the time cautery is applied without appropriate contact with adhesions, number of serious complications). Ten attending doctors were included in the experienced group and conducted the operation of simulated cholecystectomy directly. Data was collected with simulator. Data of two groups was compared. Experiment 2: Participants in inexperienced group were assigned to basic group (receiving 8 items of basic operation training) and special group (receiving 8 items of basic operation training and 4 items of specialized training), and 10 persons for each group. They received training course designed by us respectively. After training level had reached the expected target, simulated cholecystectomy was performed, and data was collected. Experimental data between basic group and special group was compared and then data between special group and experienced group was compared. Results of experiment 1 showed that there is significant difference between data in inexperienced group in which participants operated simulated cholecystectomy only according to instructors' teaching and operation video and data in experienced group. Result of experiment 2 suggested that, total operation time, number of perforations, number of serious complications, number of non-cauterized bleeding and the time cautery is applied without appropriate contact with adhesions in special group were all superior to those in basic group. There was no statistical difference on other data between special group and basic group. Comparing special group with experienced group, data of total operation time and the time cautery is applied without appropriate contact with adhesions in experienced group was superior to that in special group. There was no statistical difference on other data between special group and experienced group. Laparoscopic simulators are effective for surgical skills training. Basic courses could mainly improve operator's hand-eye coordination and perception of sense of the insertion depth for instruments. Specialized training courses could not only improve operator's familiarity with surgeries, but also reduce operation time and risk, and improve safety.

45 CFR 46.101 - To what does this policy apply?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or... SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.101 To what does this policy apply? (a) Except as provided in paragraph (b) of this section, this policy applies to all research...

45 CFR 46.101 - To what does this policy apply?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or... SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.101 To what does this policy apply? (a) Except as provided in paragraph (b) of this section, this policy applies to all research...

45 CFR 46.101 - To what does this policy apply?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or... SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.101 To what does this policy apply? (a) Except as provided in paragraph (b) of this section, this policy applies to all research...

45 CFR 46.101 - To what does this policy apply?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or... SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.101 To what does this policy apply? (a) Except as provided in paragraph (b) of this section, this policy applies to all research...

45 CFR 46.101 - To what does this policy apply?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., subpart C. The exemption at 45 CFR 46.101(b)(2), for research involving survey or interview procedures or... SUBJECTS Basic HHS Policy for Protection of Human Research Subjects § 46.101 To what does this policy apply? (a) Except as provided in paragraph (b) of this section, this policy applies to all research...

42 CFR 65a.1 - To what programs do these regulations apply?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false To what programs do these regulations apply? 65a.1..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS § 65a.1 To what programs do these regulations apply? (a) The regulations of this...

42 CFR 65a.1 - To what programs do these regulations apply?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false To what programs do these regulations apply? 65a.1..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS § 65a.1 To what programs do these regulations apply? (a) The regulations of this...

42 CFR 65a.1 - To what programs do these regulations apply?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false To what programs do these regulations apply? 65a.1..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS § 65a.1 To what programs do these regulations apply? (a) The regulations of this...

34 CFR 403.1 - What is the State Vocational and Applied Technology Education Program?

Code of Federal Regulations, 2012 CFR

2012-07-01

... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED... programs under the basic programs for vocational education authorized by title II of the Act and listed in... 34 Education 3 2012-07-01 2012-07-01 false What is the State Vocational and Applied Technology...

34 CFR 403.1 - What is the State Vocational and Applied Technology Education Program?

Code of Federal Regulations, 2014 CFR

2014-07-01

... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED... programs under the basic programs for vocational education authorized by title II of the Act and listed in... 34 Education 3 2014-07-01 2014-07-01 false What is the State Vocational and Applied Technology...

34 CFR 403.1 - What is the State Vocational and Applied Technology Education Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED... programs under the basic programs for vocational education authorized by title II of the Act and listed in... 34 Education 3 2011-07-01 2011-07-01 false What is the State Vocational and Applied Technology...

34 CFR 403.1 - What is the State Vocational and Applied Technology Education Program?

Code of Federal Regulations, 2013 CFR

2013-07-01

... (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED... programs under the basic programs for vocational education authorized by title II of the Act and listed in... 34 Education 3 2013-07-01 2013-07-01 false What is the State Vocational and Applied Technology...

Use of a New "Moodle" Module for Improving the Teaching of a Basic Course on Computer Architecture

ERIC Educational Resources Information Center

Trenas, M. A.; Ramos, J.; Gutierrez, E. D.; Romero, S.; Corbera, F.

2011-01-01

This paper describes how a new "Moodle" module, called "CTPracticals", is applied to the teaching of the practical content of a basic computer organization course. In the core of the module, an automatic verification engine enables it to process the VHDL designs automatically as they are submitted. Moreover, a straightforward…

45 CFR 260.52 - What are the basic provisions of the Family Violence Option (FVO)?

Code of Federal Regulations, 2010 CFR

2010-10-01

... Provisions Apply to Victims of Domestic Violence? § 260.52 What are the basic provisions of the Family... receiving TANF and MOE assistance with a history of domestic violence, while maintaining the confidentiality... individuals to escape domestic violence or unfairly penalize those who are or have been victimized by such...

Coherent Teaching and Need-Based Learning in Science: An Approach to Teach Engineering Students in Basic Physics Courses

ERIC Educational Resources Information Center

Kurki-Suonio, T.; Hakola, A.

2007-01-01

In the present paper, we propose an alternative, based on constructivism, to the conventional way of teaching basic physics courses at the university level. We call this approach "coherent teaching" and the underlying philosophy of teaching science and engineering "need-based learning". We have been applying this philosophy in…

Incorporating Applied Learning Techniques of Basic Skills into the Secondary Vocational Education Curriculum. Final Report.

ERIC Educational Resources Information Center

Jonesboro School District 1, AR.

The Jonesboro Area Vocational High School was the Arkansas pilot site for the Southern Regional Education Board (SREB) initiative to improve the basic competencies of high school vocational students. The project aimed to revise vocational courses to incorporate academic content, to revise course requirements, and to encourage vocational and…

Protecting the Purity of Pure Research: Organizational Boundary-Work at an Institute of Basic Research

ERIC Educational Resources Information Center

Sapir, Adi

2017-01-01

Research institutions and universities are positioned in a state of inherent struggle to reconcile the pressures and demands of the external environment with those of the scientific community. This paper is focused on one contested area, the division between basic and applied research, and explores how universities work to balance organizational…

Translating Basic Behavioral and Social Science Research to Clinical Application: The EVOLVE Mixed Methods Approach

ERIC Educational Resources Information Center

Peterson, Janey C.; Czajkowski, Susan; Charlson, Mary E.; Link, Alissa R.; Wells, Martin T.; Isen, Alice M.; Mancuso, Carol A.; Allegrante, John P.; Boutin-Foster, Carla; Ogedegbe, Gbenga; Jobe, Jared B.

2013-01-01

Objective: To describe a mixed-methods approach to develop and test a basic behavioral science-informed intervention to motivate behavior change in 3 high-risk clinical populations. Our theoretically derived intervention comprised a combination of positive affect and self-affirmation (PA/SA), which we applied to 3 clinical chronic disease…

Clusters and Factors Associated with Complementary Basic Education in Tanzania Mainland

ERIC Educational Resources Information Center

Edwin, Paul; Amina, Msengwa S.; Godwin, Naimani M.

2017-01-01

Complimentary Basic Education in Tanzania (COBET) is a community-based programme initiated in 1999 to provide formal education system opportunity to over aged children or children above school age. The COBET program was analyzed using secondary data collected from 21 regions from 2008 to 2012. Cluster analysis was applied to classify the 21…

45 CFR 260.52 - What are the basic provisions of the Family Violence Option (FVO)?

Code of Federal Regulations, 2011 CFR

2011-10-01

... Provisions Apply to Victims of Domestic Violence? § 260.52 What are the basic provisions of the Family... receiving TANF and MOE assistance with a history of domestic violence, while maintaining the confidentiality... individuals to escape domestic violence or unfairly penalize those who are or have been victimized by such...

48 CFR 35.014 - Government property and title.

Code of Federal Regulations, 2011 CFR

2011-10-01

... basic or applied scientific research, apply to contracts with nonprofit institutions of higher education and nonprofit organizations whose primary purpose is the conduct of scientific research: (1) If the... SPECIAL CATEGORIES OF CONTRACTING RESEARCH AND DEVELOPMENT CONTRACTING 35.014 Government property and...

45 CFR 63.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... services. Such information is obtained through the conduct of basic and applied research, statistical... apply to all grant awards of Federal assistance made by the Assistant Secretary for Planning and... may be delegated to the Assistant Secretary for policy research activities. (b) Exceptions to...

Drug policy, harm and human rights: a rationalist approach.

PubMed

Stevens, Alex

2011-05-01

It has recently been argued that drug-related harms cannot be compared, so making it impossible to choose rationally between various drug policy options. Attempts to apply international human rights law to this area are valid, but have found it difficult to overcome the problems in applying codified human rights to issues of drug policy. This article applies the rationalist ethical argument of Gewirth (1978) to this issue. It outlines his argument to the 'principle of generic consistency' and the hierarchy of basic, nonsubtractive and additive rights that it entails. It then applies these ideas to drug policy issues, such as whether there is a right to use drugs, whether the rights of drug 'addicts' can be limited, and how different harms can be compared in choosing between policies. There is an additive right to use drugs, but only insofar as this right does not conflict with the basic and nonsubtractive rights of others. People whose freedom to choose whether to use drugs is compromised by compulsion have a right to receive treatment. They retain enforceable duties not to inflict harms on others. Policies which reduce harms to basic and nonsubtractive rights should be pursued, even if they lead to harms to additive rights. There exists a sound, rational, extra-legal basis for the discussion of drug policy and related harms which enables commensurable discussion of drug policy options. Copyright © 2011 Elsevier B.V. All rights reserved.

The Applied Behavior Analysis Research Paradigm and Single-Subject Designs in Adapted Physical Activity Research.

PubMed

Haegele, Justin A; Hodge, Samuel Russell

2015-10-01

There are basic philosophical and paradigmatic assumptions that guide scholarly research endeavors, including the methods used and the types of questions asked. Through this article, kinesiology faculty and students with interests in adapted physical activity are encouraged to understand the basic assumptions of applied behavior analysis (ABA) methodology for conducting, analyzing, and presenting research of high quality in this paradigm. The purposes of this viewpoint paper are to present information fundamental to understanding the assumptions undergirding research methodology in ABA, describe key aspects of single-subject research designs, and discuss common research designs and data-analysis strategies used in single-subject studies.

Basic and applied research program. Semiannual report, July-December 1978

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

Butler, B.L.

1979-12-01

The status of research projects in the Basic and Applied Research Program at SERI is presented for the semiannual period ending December 31, 1978. The five tasks in this program are grouped into Materials Research and Development, Materials Processing and Development, Photoconversion Research, Exploratory Research, and Energy Resource and Assessment and have been carried out by personnel in the Materials, Bio/Chemical Conversion, and Energy Resource and Assessment Branches. Subtask elements in the task areas include coatings and films, polymers, metallurgy and corrosion, optical materials, surfaces and interfaces in materials research and development; photochemistry, photoelectrochemistry, and photobiology in photoconversion; thin glassmore » mirror development, silver degradation of mirrors, hail resistance of thin glass, thin glass manufacturing, cellular glass development, and sorption by desiccants in materials processing and development; and thermoelectric energy conversion, desiccant cooling, photothermal degradation, and amorphous materials in exploratory research. For each task or subtask element, the overview, scope, goals, approach, apparatus and equipment, and supporting subcontracts are presented, as applicable, in addition to the status of the projects in each task or subtask. Listing of publications and reports authored by personnel associated with the Basic and Applied Research Program and prepared or published during 1978 are also included.« less

Evolving the future: Toward a science of intentional change

PubMed Central

Wilson, David Sloan; Hayes, Steven C.; Biglan, Anthony; Embry, Dennis D.

2015-01-01

Humans possess great capacity for behavioral and cultural change, but our ability to manage change is still limited. This article has two major objectives: first, to sketch a basic science of intentional change centered on evolution; second, to provide examples of intentional behavioral and cultural change from the applied behavioral sciences, which are largely unknown to the basic sciences community. All species have evolved mechanisms of phenotypic plasticity that enable them to respond adaptively to their environments. Some mechanisms of phenotypic plasticity count as evolutionary processes in their own right. The human capacity for symbolic thought provides an inheritance system having the same kind of combinatorial diversity as does genetic recombination and antibody formation. Taking these propositions seriously allows an integration of major traditions within the basic behavioral sciences, such as behaviorism, social constructivism, social psychology, cognitive psychology, and evolutionary psychology, which are often isolated and even conceptualized as opposed to one another. The applied behavioral sciences include well-validated examples of successfully managing behavioral and cultural change at scales ranging from individuals to small groups to large populations. However, these examples are largely unknown beyond their disciplinary boundaries, for lack of a unifying theoretical framework. Viewed from an evolutionary perspective, they are examples of managing evolved mechanisms of phenotypic plasticity, including open-ended processes of variation and selection. Once the many branches of the basic and applied behavioral sciences become conceptually unified, we are closer to a science of intentional change than one might think. PMID:24826907

Basic Sciences Fertilizing Clinical Microbiology and Infection Management.

PubMed

Baquero, Fernando

2017-08-15

Basic sciences constitute the most abundant sources of creativity and innovation, as they are based on the passion of knowing. Basic knowledge, in close and fertile contact with medical and public health needs, produces distinct advancements in applied sciences. Basic sciences play the role of stem cells, providing material and semantics to construct differentiated tissues and organisms and enabling specialized functions and applications. However, eventually processes of "practice deconstruction" might reveal basic questions, as in de-differentiation of tissue cells. Basic sciences, microbiology, infectious diseases, and public health constitute an epistemological gradient that should also be an investigational continuum. The coexistence of all these interests and their cross-fertilization should be favored by interdisciplinary, integrative research organizations working simultaneously in the analytical and synthetic dimensions of scientific knowledge. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Three basic principles of success.

PubMed

Levin, Roger

2003-06-01

Basic business principles all but ensure success when they are followed consistently. Putting strategies, objectives and tactics in place is the first step toward being able to document systems, initiate scripting and improve staff training. Without the basic steps, systems, scripting and training the practice for performance would be hit or miss, at best. More importantly, applying business principles ensures that limited practice resources are dedicated to the achievement of the strategy. By following this simple, three-step process, a dental practice can significantly enhance both financial success and dentist and staff satisfaction.

42 CFR 23.8 - What operational requirements apply to an entity to which National Health Service Corps personnel...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false What operational requirements apply to an entity to... Assignment of National Health Service Corps Personnel § 23.8 What operational requirements apply to an entity...; and (g) Establish basic data, cost accounting, and management information and reporting systems as...

Integrated design course of applied optics focusing on operating and maintaining abilities

NASA Astrophysics Data System (ADS)

Xu, Zhongjie; Ning, Yu; Jiang, Tian; Cheng, Xiangai

2017-08-01

The abilities of operating and maintaining optical instruments are crucial in modern society. Besides the basic knowledge in optics, the optics courses in the National University of Defense Technology also focus on the training on handling typical optical equipment. As the link between classroom courses on applied optics and the field trips, the integrated design course of applied optics aims to give the students a better understanding on several instantly used optical equipment, such as hand-held telescope and periscope, etc. The basic concepts of optical system design are also emphasized as well. The course is arranged rightly after the classroom course of applied optics and composed of experimental and design tasks. The experimental tasks include the measurements of aberrations and major parameters of a primitive telescope, while in the design parts, the students are asked to design a Keplerian telescope. The whole course gives a deepened understandings on the concepts, assembling, and operating of telescopes. The students are also encouraged to extend their interests on other typical optical instruments.

Student Difficulties Measuring Distances in Terms of Wavelength: Lack of Basic Skills or Failure to Transfer?

ERIC Educational Resources Information Center

Kryjevskaia, Mila; Stetzer, MacKenzie R.; Heron, Paula R. L.

2013-01-01

In a previous paper that focused on the transmission of periodic waves at the boundary between two media, we documented difficulties with the basic concepts of wavelength, frequency, and propagation speed, and with the relationship v=f[lambda]. In this paper, we report on student attempts to apply this relationship in problems involving two-source…

Effects of Game Design Patterns on Basic Life Support Training Content

ERIC Educational Resources Information Center

Kelle, Sebastian; Klemke, Roland; Specht, Marcus

2013-01-01

Based on a previous analysis of game design patterns and related effects in an educational scenario, the following paper presents an experimental study. In the study a course for Basic Life Support training has been evaluated and two game design patterns have been applied to the course. The hypotheses evaluated in this paper relate to game design…

Making Basic Math Skills Work for You in Marketing. Student Manual and Laboratory Guide.

ERIC Educational Resources Information Center

Klewer, Edwin D.

This student manual and workbook is the second part of a mathematics series for use with high school students. The manual is to be used to apply the mathematics skills that students have learned in a first part called "Developing Basic Math Skills for Marketing." The manual presents conceptual instruction in mathematics in a competency based…

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

Mather, James

Atmospheric Radiation Measurement (ARM) Program standard data format is NetCDF 3 (Network Common Data Form). The object of this tutorial is to provide a basic introduction to NetCDF with an emphasis on aspects of the ARM application of NetCDF. The goal is to provide basic instructions for reading and visualizing ARM NetCDF data with the expectation that these examples can then be applied to more complex applications.

Learnings from an Entrepreneur: How to Start a Consulting Practice

NASA Astrophysics Data System (ADS)

Bowes, Debra

2013-03-01

There are important basic learnings I have experienced in starting my own consulting practice over 7 years ago. These learnings will help you maximize your value, reduce competition and build your reputation and business income. I believe these can apply to many fields but certainly for the Life Sciences. A few of the basic I will cover are

Bling My Research! A Mock Grant Panel Activity Illustrating the Importance of Basic Research

ERIC Educational Resources Information Center

Leander, Celeste A.; Whitton, Jeannette

2010-01-01

First-year university students have misconceptions about the source and dynamics of publicly funded research money. We designed an activity in which students take part in a mock grant panel. The results indicated a strong tendency toward student funding of applied medical research at the expense of basic research. Exposure to a few examples of…

Basic Radio Circuits and Vacuum Tube AM Troubleshooting; Radio and Television Service, Intermediate: 9785.03.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

The 135-hour quinmester course covers study of basic radio circuits as applied to vacuum tube radios in six blocks of instruction: orientation; AM receivers with tubes; no signal, audio failure; distortion; weak, noisy signals; and a post-test. Each block is subdivided into several units, and block objectives are outlined. Completion of AC…

Applied Academic Skills in Vocational and Nonvocational Classrooms: A Classroom Observation and Focus Group Study.

ERIC Educational Resources Information Center

Watkins, Larae

After 2 years of a 5-year pilot project to develop approaches to strengthen basic competencies of students enrolled in vocational programs in Oklahoma, two of the projects were reviewed. The study sought to: (1) document the incidence and level of basic skills instruction, along with the teaching methods and materials used, in the vocational and…

21 CFR 820.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... used in, and the facilities and controls used for, the design, manufacture, packaging, labeling... compliance with the Federal Food, Drug, and Cosmetic Act (the act). This part establishes basic requirements... controls apply only to those devices listed in § 820.30(a)(2). This regulation does not apply to...

21 CFR 820.1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... used in, and the facilities and controls used for, the design, manufacture, packaging, labeling... compliance with the Federal Food, Drug, and Cosmetic Act (the act). This part establishes basic requirements... controls apply only to those devices listed in § 820.30(a)(2). This regulation does not apply to...

21 CFR 820.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... used in, and the facilities and controls used for, the design, manufacture, packaging, labeling... compliance with the Federal Food, Drug, and Cosmetic Act (the act). This part establishes basic requirements... controls apply only to those devices listed in § 820.30(a)(2). This regulation does not apply to...

21 CFR 820.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... used in, and the facilities and controls used for, the design, manufacture, packaging, labeling... compliance with the Federal Food, Drug, and Cosmetic Act (the act). This part establishes basic requirements... controls apply only to those devices listed in § 820.30(a)(2). This regulation does not apply to...

Financial Aid: The Student Guide, 2000-2001.

ERIC Educational Resources Information Center

Department of Education, Washington, DC.

This publication presents a basic summary of student financial assistance programs provided by the federal government and explains how to apply for them. It begins by reviewing sources of information about student aid. A general information section covers student eligibility, financial need, dependency status, applying, special circumstances,…

34 CFR 97.101 - To what does this policy apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.101... applies to all research involving human subjects conducted, supported or otherwise subject to regulation...

34 CFR 97.101 - To what does this policy apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.101... applies to all research involving human subjects conducted, supported or otherwise subject to regulation...

34 CFR 97.101 - To what does this policy apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.101... applies to all research involving human subjects conducted, supported or otherwise subject to regulation...

34 CFR 97.101 - To what does this policy apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.101... applies to all research involving human subjects conducted, supported or otherwise subject to regulation...

34 CFR 97.101 - To what does this policy apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.101... applies to all research involving human subjects conducted, supported or otherwise subject to regulation...

42 CFR 52.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2010 CFR

2010-10-01

... consist of laboratory, clinical, population, field, statistical, basic, applied or other types of...) Activities conducted by, or in cooperation with, the World Health Organization, and (2) With respect to... Health Organization or the World Health Organization. [61 FR 55105, Oct. 24, 1996] ...

34 CFR 1100.5 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., volunteer or professional experience in the adult literacy, family literacy, adult education, or related... more of the following activities in literacy or education or education related fields: basic and... 34 Education 4 2011-07-01 2011-07-01 false What definitions apply? 1100.5 Section 1100.5 Education...

On the effect of basic and acidic additives on the separation of the enantiomers of some basic drugs with polysaccharide-based chiral selectors and polar organic mobile phases.

PubMed

Mosiashvili, L; Chankvetadze, L; Farkas, T; Chankvetadze, B

2013-11-22

This article reports the systematic study of the effect of basic and acidic additives on HPLC separation of enantiomers of some basic chiral drugs on polysaccharide-based chiral columns under polar organic mobile-phase conditions. In contrary to generally accepted opinion that the basic additives improve the separation of enantiomers of basic compounds, the multiple scenarios were observed including the increase, decrease, disappearance and appearance of separation, as well as the reversal of the enantiomer elution order of studied basic compounds induced by the acidic additives. These effects were observed on most of the studied 6 chiral columns in 2-propanol and acetonitrile as mobile phases and diethylamine as a basic additive. As acidic additives formic acid was used systematically and acetic acid and trifluoroacetic acid were applied for comparative purposes. This study illustrates that the minor acidic additives to the mobile phase can be used as for the adjustment of separation selectivity and the enantiomer elution order of basic compounds, as well as for study of chiral recognition mechanisms with polysaccharide-based chiral stationary phases. Copyright © 2013 Elsevier B.V. All rights reserved.

A generalized concept for cost-effective structural design. [Statistical Decision Theory applied to aerospace systems

NASA Technical Reports Server (NTRS)

Thomas, J. M.; Hawk, J. D.

1975-01-01

A generalized concept for cost-effective structural design is introduced. It is assumed that decisions affecting the cost effectiveness of aerospace structures fall into three basic categories: design, verification, and operation. Within these basic categories, certain decisions concerning items such as design configuration, safety factors, testing methods, and operational constraints are to be made. All or some of the variables affecting these decisions may be treated probabilistically. Bayesian statistical decision theory is used as the tool for determining the cost optimum decisions. A special case of the general problem is derived herein, and some very useful parametric curves are developed and applied to several sample structures.

Learning theories 101: application to everyday teaching and scholarship.

PubMed

Kay, Denise; Kibble, Jonathan

2016-03-01

Shifts in educational research, in how scholarship in higher education is defined, and in how funding is appropriated suggest that educators within basic science fields can benefit from increased understanding of learning theory and how it applies to classroom practice. This article uses a mock curriculum design scenario as a framework for the introduction of five major learning theories. Foundational constructs and principles from each theory and how they apply to the proposed curriculum designs are described. A summative table that includes basic principles, constructs, and classroom applications as well as the role of the teacher and learner is also provided for each theory. Copyright © 2016 The American Physiological Society.

Systems and methods for knowledge discovery in spatial data

DOEpatents

Obradovic, Zoran; Fiez, Timothy E.; Vucetic, Slobodan; Lazarevic, Aleksandar; Pokrajac, Dragoljub; Hoskinson, Reed L.

2005-03-08

Systems and methods are provided for knowledge discovery in spatial data as well as to systems and methods for optimizing recipes used in spatial environments such as may be found in precision agriculture. A spatial data analysis and modeling module is provided which allows users to interactively and flexibly analyze and mine spatial data. The spatial data analysis and modeling module applies spatial data mining algorithms through a number of steps. The data loading and generation module obtains or generates spatial data and allows for basic partitioning. The inspection module provides basic statistical analysis. The preprocessing module smoothes and cleans the data and allows for basic manipulation of the data. The partitioning module provides for more advanced data partitioning. The prediction module applies regression and classification algorithms on the spatial data. The integration module enhances prediction methods by combining and integrating models. The recommendation module provides the user with site-specific recommendations as to how to optimize a recipe for a spatial environment such as a fertilizer recipe for an agricultural field.

10 CFR Appendix A to Part 4 - Federal Financial Assistance to Which This Part Applies 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... recovery, in meetings, conferences, workshops, and symposia to assist scientific, professional or educational institutions or groups. (e) Research Support. Agreements for the financial support of basic and applied scientific research and for the exchange of scientific information. [29 FR 19277, Dec. 31, 1964...

10 CFR Appendix A to Part 4 - Federal Financial Assistance to Which This Part Applies 1

Code of Federal Regulations, 2013 CFR

2013-01-01

... recovery, in meetings, conferences, workshops, and symposia to assist scientific, professional or educational institutions or groups. (e) Research Support. Agreements for the financial support of basic and applied scientific research and for the exchange of scientific information. [29 FR 19277, Dec. 31, 1964...

MPA-11: Materials Synthesis and Integrated Devices; Overview of an Applied Energy Group

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

Dattelbaum, Andrew Martin

Our mission is to provide innovative and creative chemical synthesis and materials science solutions to solve materials problems across the LANL missions. Our group conducts basic and applied research in areas related to energy security as well as problems relevant to the Weapons Program.

Thermodynamic Laws Applied to Economic Systems

ERIC Educational Resources Information Center

González, José Villacís

2009-01-01

Economic activity in its different manifestations--production, exchange, consumption and, particularly, information on quantities and prices--generates and transfers energy. As a result, we can apply to it the basic laws of thermodynamics. These laws are applicable within a system, i.e., in a country or between systems and countries. To these…

Applied oceanography

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

Bishop, J.M.

This book combines oceanography principles and applications such as marine pollution, resources, and transportation. It is divided into two main parts treating the basic principles of physical oceanography, and presenting a unique systems framework showing how physical oceanography, marine ecology, economics, and government policy may be combined to define the newly developing field of applied oceanography.

10 CFR Appendix A to Part 4 - Federal Financial Assistance to Which This Part Applies 1

Code of Federal Regulations, 2011 CFR

2011-01-01

... recovery, in meetings, conferences, workshops, and symposia to assist scientific, professional or educational institutions or groups. (e) Research Support. Agreements for the financial support of basic and applied scientific research and for the exchange of scientific information. [29 FR 19277, Dec. 31, 1964...

10 CFR Appendix A to Part 4 - Federal Financial Assistance to Which This Part Applies 1

Code of Federal Regulations, 2010 CFR

2010-01-01

... recovery, in meetings, conferences, workshops, and symposia to assist scientific, professional or educational institutions or groups. (e) Research Support. Agreements for the financial support of basic and applied scientific research and for the exchange of scientific information. [29 FR 19277, Dec. 31, 1964...

The Northeast Texas Adult Education Rural Workplace Literacy Program. Annual Performance Report.

ERIC Educational Resources Information Center

Barker, Sue; Burns, Kathryn; Bowers, Jana; Pruitt, Jeanni; Pate, Sally

The Northeast Texas Adult Education Rural Education Workplace Literacy Program, which is a partnership between Northeast Texas Community College and area businesses, offers workplace literacy instruction designed around job-specific basic skills. Training is offered in the following: applied workplace technology; applied math skills; measurements…

48 CFR 970.5217-1 - Work for Others Program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... selection is based on merit or peer review, the work involves basic or applied research to further advance... all Work for Others projects in accordance with the standards, policies, and procedures that apply to..., safeguards and classification procedures, and human and animal research regulations; (8) May subcontract...

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

Stein, R.L.

A procedure for the analysis of observed isotope effects on rates of complex reactions is outlined which can be applied to kinetic isotope effect data for any reaction having a virtual transition state whose structure can be varied by adjusting a reaction parameter. This procedure is applied to the basic hydrolysis of p-nitroacetanilide. 3 tables. (DLC)

42 CFR 65a.5 - How to apply.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false How to apply. 65a.5 Section 65a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS...

42 CFR 65a.5 - How to apply.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false How to apply. 65a.5 Section 65a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS...

42 CFR 65a.5 - How to apply.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false How to apply. 65a.5 Section 65a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS...

42 CFR 65a.5 - How to apply.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false How to apply. 65a.5 Section 65a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS...

42 CFR 65a.5 - How to apply.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false How to apply. 65a.5 Section 65a.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH AND TRAINING GRANTS...

Primary Events in vision - Investigation of Basic Eye Responses.

DTIC Science & Technology

1983-06-30

Lewis School of Applied & Engineering Physics CORNELL UNIVERSITY Ithaca, NY 30 JUNE 1983 SEF 2 PHASE REPORT Contract No. N62269.62-M-3270 APPROVED FOR...Ph.D. N62269-82-M-3270 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK School of Applied & Engineering Physics AREA

40 CFR 26.101 - To what does this policy apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by EPA § 26... policy applies to all research involving human subjects conducted, supported or otherwise subject to...

40 CFR 26.101 - To what does this policy apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by EPA § 26... policy applies to all research involving human subjects conducted, supported or otherwise subject to...

40 CFR 26.101 - To what does this policy apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by EPA § 26... policy applies to all research involving human subjects conducted, supported or otherwise subject to...

40 CFR 26.101 - To what does this policy apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by EPA § 26... policy applies to all research involving human subjects conducted, supported or otherwise subject to...

40 CFR 26.101 - To what does this policy apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

...), for research involving survey or interview procedures or observation of public behavior, does not... SUBJECTS Basic EPA Policy for Protection of Subjects in Human Research Conducted or Supported by EPA § 26... policy applies to all research involving human subjects conducted, supported or otherwise subject to...

34 CFR 461.4 - What regulations apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 3 2012-07-01 2012-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

34 CFR 461.5 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 3 2012-07-01 2012-07-01 false What definitions apply? 461.5 Section 461.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.5 What...

34 CFR 461.5 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 3 2014-07-01 2014-07-01 false What definitions apply? 461.5 Section 461.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.5 What...

34 CFR 461.5 - What definitions apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What definitions apply? 461.5 Section 461.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.5 What...

34 CFR 461.4 - What regulations apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 3 2013-07-01 2013-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

34 CFR 461.4 - What regulations apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

34 CFR 461.5 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 3 2013-07-01 2013-07-01 false What definitions apply? 461.5 Section 461.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.5 What...

34 CFR 461.5 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What definitions apply? 461.5 Section 461.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.5 What...

34 CFR 461.4 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

34 CFR 461.4 - What regulations apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 3 2014-07-01 2014-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

Matematicas en la vida actual. Volumen II, edicion para el maestro. (Mathematics: A Practical View. Volume II, Teacher Edition). Applied Basic Curriculum Series.

ERIC Educational Resources Information Center

Evaluation, Dissemination and Assessment Center, Dallas.

This Spanish language teacher's edition of a practical mathematics text for the intermediate grades contains three components which can be structured in different combinations according to different student needs. Built around a review of selected objectives in the mathematics basic curriculum, the material is intended to stimulate interest in…

Matematicas en la vida actual. Volumen I, edicion para el maestro. (Mathematics: A Practical View. Volume I, Teacher Edition). Applied Basic Curriculum Series.

ERIC Educational Resources Information Center

Evaluation, Dissemination and Assessment Center, Dallas.

This Spanish language teacher's edition of a practical mathematics text for the intermediate grades contains three components which can be structured in different combinations according to different student needs. Built around a review of selected objectives in the mathematics basic curriculum, the material is intended to stimulate interest in…

Matematicas en la vida actual. Volumen III, edicion para el maestro. (Mathematics: A Practical View. Volume III, Teacher Edition). Applied Basic Curriculum Series.

ERIC Educational Resources Information Center

Evaluation, Dissemination and Assessment Center, Dallas.

This Spanish language teacher's edition of a practical mathematics text for the intermediate grades contains three components which can be structured in different combinations according to different student needs. Built around a review of selected objectives in the mathematics basic curriculum, the material is intended to stimulate interest in…

The Primary Student Teachers' Views about a Blended Learning Application in a Basic Physics Course

ERIC Educational Resources Information Center

Taskin Ekici, Fatma; Kara, Izzet; Ekici, Erhan

2012-01-01

In this study we present an overview of the undergraduate blended Physics course that has been supported by the Moodle platform. The course that has been applied is a basic physics course for primary student teachers. The aim of Moodle is to create an online learning environment which helps students to have a virtual space where they can share…

24 CFR 200.926e - Supplemental information for use with the CABO One and Two Family Dwelling Code.

Code of Federal Regulations, 2014 CFR

2014-04-01

... shall be in accordance with section 7 of ASCE 7-88. (c) Wind pressures. The minimum Design Wind Pressures (net pressures) set forth below apply to areas designated as experiencing basic wind speeds up to and including 80 mph, as shown in ASCE 7-88, Figure 1, Basic Wind Speed Map. These pressures also...

24 CFR 200.926e - Supplemental information for use with the CABO One and Two Family Dwelling Code.

Code of Federal Regulations, 2013 CFR

2013-04-01

... shall be in accordance with section 7 of ASCE 7-88. (c) Wind pressures. The minimum Design Wind Pressures (net pressures) set forth below apply to areas designated as experiencing basic wind speeds up to and including 80 mph, as shown in ASCE 7-88, Figure 1, Basic Wind Speed Map. These pressures also...

24 CFR 200.926e - Supplemental information for use with the CABO One and Two Family Dwelling Code.

Code of Federal Regulations, 2012 CFR

2012-04-01

... shall be in accordance with section 7 of ASCE 7-88. (c) Wind pressures. The minimum Design Wind Pressures (net pressures) set forth below apply to areas designated as experiencing basic wind speeds up to and including 80 mph, as shown in ASCE 7-88, Figure 1, Basic Wind Speed Map. These pressures also...

Pre-Eminent Curriculum in Islamic Basic School Integrated Comparative Studies in Islamic Basic School Integrated Al-Izzah Serang and Al-Hanif Cilegon, Banten, Indonesia

ERIC Educational Resources Information Center

Fauz, Anis; Hasbullah

2016-01-01

Compare to General SD (Primary school), the superiority of SD Islam Terpadu (Integrated Islamic Primary School) lies on the development of the curriculum and learning that is more emphasize on integrated curriculum and integrated learning. Curriculum model applied in Sekolah Dasar Islam Terpadu (SDIT) is integrated curriculum. This curriculum is…

Behavioral Economics

PubMed Central

Niileksela, Christopher R.; Kaplan, Brent A.

2013-01-01

In recent years, behavioral economics has gained much attention in psychology and public policy. Despite increased interest and continued basic experimental studies, the application of behavioral economics to therapeutic settings remains relatively sparse. Using examples from both basic and applied studies, we provide an overview of the principles comprising behavioral economic perspectives and discuss implications for behavior analysts in practice. A call for further translational research is provided. PMID:25729506

24 CFR 200.926e - Supplemental information for use with the CABO One and Two Family Dwelling Code.

Code of Federal Regulations, 2010 CFR

2010-04-01

... shall be in accordance with section 7 of ASCE 7-88. (c) Wind pressures. The minimum Design Wind Pressures (net pressures) set forth below apply to areas designated as experiencing basic wind speeds up to and including 80 mph, as shown in ASCE 7-88, Figure 1, Basic Wind Speed Map. These pressures also...

24 CFR 200.926e - Supplemental information for use with the CABO One and Two Family Dwelling Code.

Code of Federal Regulations, 2011 CFR

2011-04-01

... shall be in accordance with section 7 of ASCE 7-88. (c) Wind pressures. The minimum Design Wind Pressures (net pressures) set forth below apply to areas designated as experiencing basic wind speeds up to and including 80 mph, as shown in ASCE 7-88, Figure 1, Basic Wind Speed Map. These pressures also...

Longitudinal Relations between Perceived Autonomy Support and Basic Need Satisfaction in Two Student Cohorts

ERIC Educational Resources Information Center

Diseth, Åge; Breidablik, Hans Johan; Meland, Eivind

2018-01-01

The relation between autonomy support and basic need satisfaction was investigated by applying a longitudinal design at a time interval of two years, and by comparing two different grade level cohorts of students. Participants comprised 1.225 Norwegian students divided by two subsamples (6th and 8th grade level/8th and 10th grade level). The…

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs.

PubMed

Murakami, S; Takayama, S; Kitamura, M; Shimabukuro, Y; Yanagi, K; Ikezawa, K; Saho, T; Nozaki, T; Okada, H

2003-02-01

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

Application of visual basic in high-throughput mass spectrometry-directed purification of combinatorial libraries.

PubMed

Li, B; Chan, E C Y

2003-01-01

We present an approach to customize the sample submission process for high-throughput purification (HTP) of combinatorial parallel libraries using preparative liquid chromatography electrospray ionization mass spectrometry. In this study, Visual Basic and Visual Basic for Applications programs were developed using Microsoft Visual Basic 6 and Microsoft Excel 2000, respectively. These programs are subsequently applied for the seamless electronic submission and handling of data for HTP. Functions were incorporated into these programs where medicinal chemists can perform on-line verification of the purification status and on-line retrieval of postpurification data. The application of these user friendly and cost effective programs in our HTP technology has greatly increased our work efficiency by reducing paper work and manual manipulation of data.

Basic science in a predoctoral family practice curriculum.

PubMed

Davies, T C; Barnett, B L

1978-02-01

A course in applied basic science was designed with topic material organized according to anatomic body regions. Details of the diagnostic method were explained early in the course, and clinical procedures for data gathering and problem analyzing were followed while the significance of basic science knowledge in dealing with clinical situations was described. A collection of 35mm slides constituted the focal point of the course. The authors conducted the course together and an atmosphere of intellectual honesty was developed through open discussion between faculty and students. Student curiosity was respected and rewarded. Summaries of the discussions were prepared retrospectively by the faculty instructors for review gy the students. This experience proved that family physicians can demonstrate effectively the relevance of basic science to clinical medicine.

Basic science research and education: a priority for training and capacity building in developing countries.

PubMed

Deckelbaum, Richard J; Ntambi, James M; Wolgemuth, Debra J

2011-09-01

This article provides evidence that basic science research and education should be key priorities for global health training, capacity building, and practice. Currently, there are tremendous gaps between strong science education and research in developed countries (the North) as compared to developing countries (the South). In addition, science research and education appear as low priorities in many developing countries. The need to stress basic science research beyond the typical investment of infectious disease basic service and research laboratories in developing areas is significant in terms of the benefits, not only to education, but also for economic strengthening and development of human resources. There are some indications that appreciation of basic science research education and training is increasing, but this still needs to be applied more rigorously and strengthened systematically in developing countries. Copyright © 2011 Elsevier Inc. All rights reserved.

Fish passage research: S.O. Conte Anadromous Fish Research Laboratory

USGS Publications Warehouse

Garebedian, Steve

2008-01-01

The Leetown Science Center’s S.O. Conte Anadromous Fish Research Laboratory conducts basic and applied scientific studies of fish passage and migration to define underlying principles and relationships of fish behavior and hydraulics, and to develop integrated, predictive research that can be applied to a wide range of fish passage problems.

42 CFR 65a.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Who is eligible to apply for a grant? 65a.3 Section 65a.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH...

42 CFR 65a.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Who is eligible to apply for a grant? 65a.3 Section 65a.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH...

42 CFR 65a.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Who is eligible to apply for a grant? 65a.3 Section 65a.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH...

42 CFR 59a.7 - Other HHS regulations that apply.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Other HHS regulations that apply. 59a.7 Section 59a.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL LIBRARY OF MEDICINE GRANTS Grants for Establishing, Expanding, and Improving Basic Resources § 59a.7 Other...

Standards for Cataloging Nonprint Materials. Fourth Edition. An Interpretation and Practical Application.

ERIC Educational Resources Information Center

Tillin, Alma M.; Quinly, William J.

Standards established by the Association for Educational Communications and Technology (AECT) set forth basic cataloging rules that apply to all types of nonprint materials. Included are all elements needed to identify, describe, and retrieve an article. Cataloging rules are applied to 18 specific media formats including audiorecording, films,…

34 CFR 403.117 - What definitions apply to the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the Basic Programs? Secondary, Postsecondary, and Adult Vocational Education Programs § 403.117 What... 34 Education 3 2014-07-01 2014-07-01 false What definitions apply to the Postsecondary and Adult... of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE...

34 CFR 403.117 - What definitions apply to the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the Basic Programs? Secondary, Postsecondary, and Adult Vocational Education Programs § 403.117 What... 34 Education 3 2013-07-01 2013-07-01 false What definitions apply to the Postsecondary and Adult... of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE...

34 CFR 403.117 - What definitions apply to the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Basic Programs? Secondary, Postsecondary, and Adult Vocational Education Programs § 403.117 What... 34 Education 3 2011-07-01 2011-07-01 false What definitions apply to the Postsecondary and Adult... of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE...

34 CFR 403.117 - What definitions apply to the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the Basic Programs? Secondary, Postsecondary, and Adult Vocational Education Programs § 403.117 What... 34 Education 3 2012-07-01 2012-07-01 false What definitions apply to the Postsecondary and Adult... of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE...

34 CFR 403.117 - What definitions apply to the Postsecondary and Adult Vocational Education Programs?

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Basic Programs? Secondary, Postsecondary, and Adult Vocational Education Programs § 403.117 What... 34 Education 3 2010-07-01 2010-07-01 false What definitions apply to the Postsecondary and Adult... of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE...

The Graduate Training Programme "Molecular Imaging for the Analysis of Gene and Protein Expression": A Case Study with an Insight into the Participation of Universities of Applied Sciences

ERIC Educational Resources Information Center

Hafner, Mathias

2008-01-01

Cell biology and molecular imaging technologies have made enormous progress in basic research. However, the transfer of this knowledge to the pharmaceutical drug discovery process, or even therapeutic improvements for disorders such as neuronal diseases, is still in its infancy. This transfer needs scientists who can integrate basic research with…

A brain-based account of “basic-level” concepts

PubMed Central

Bauer, Andrew James; Just, Marcel Adam

2017-01-01

This study provides a brain-based account of how object concepts at an intermediate (basic) level of specificity are represented, offering an enriched view of what it means for a concept to be a basic-level concept, a research topic pioneered by Rosch and others (Rosch et al., 1976). Applying machine learning techniques to fMRI data, it was possible to determine the semantic content encoded in the neural representations of object concepts at basic and subordinate levels of abstraction. The representation of basic-level concepts (e.g. bird) was spatially broad, encompassing sensorimotor brain areas that encode concrete object properties, and also language and heteromodal integrative areas that encode abstract semantic content. The representation of subordinate-level concepts (robin) was less widely distributed, concentrated in perceptual areas that underlie concrete content. Furthermore, basic-level concepts were representative of their subordinates in that they were neurally similar to their typical but not atypical subordinates (bird was neurally similar to robin but not woodpecker). The findings provide a brain-based account of the advantages that basic-level concepts enjoy in everyday life over subordinate-level concepts: the basic level is a broad topographical representation that encompasses both concrete and abstract semantic content, reflecting the multifaceted yet intuitive meaning of basic-level concepts. PMID:28826947

A brain-based account of "basic-level" concepts.

PubMed

Bauer, Andrew James; Just, Marcel Adam

2017-11-01

This study provides a brain-based account of how object concepts at an intermediate (basic) level of specificity are represented, offering an enriched view of what it means for a concept to be a basic-level concept, a research topic pioneered by Rosch and others (Rosch et al., 1976). Applying machine learning techniques to fMRI data, it was possible to determine the semantic content encoded in the neural representations of object concepts at basic and subordinate levels of abstraction. The representation of basic-level concepts (e.g. bird) was spatially broad, encompassing sensorimotor brain areas that encode concrete object properties, and also language and heteromodal integrative areas that encode abstract semantic content. The representation of subordinate-level concepts (robin) was less widely distributed, concentrated in perceptual areas that underlie concrete content. Furthermore, basic-level concepts were representative of their subordinates in that they were neurally similar to their typical but not atypical subordinates (bird was neurally similar to robin but not woodpecker). The findings provide a brain-based account of the advantages that basic-level concepts enjoy in everyday life over subordinate-level concepts: the basic level is a broad topographical representation that encompasses both concrete and abstract semantic content, reflecting the multifaceted yet intuitive meaning of basic-level concepts. Copyright © 2017 Elsevier Inc. All rights reserved.

48 CFR 1834.201 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... engineering support services, steady state operations, basic and applied research, and routine services such... American National Standards Institute/Electronics Industries Alliance (ANSI/EIA) Standard-748, Earned Value...

48 CFR 1834.201 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... engineering support services, steady state operations, basic and applied research, and routine services such... American National Standards Institute/Electronics Industries Alliance (ANSI/EIA) Standard-748, Earned Value...

Microgravity: A New Tool for Basic and Applied Research in Space

NASA Technical Reports Server (NTRS)

1985-01-01

This brochure highlights selected aspects of the NASA Microgravity Science and Applications program. So that we can expand our understanding and control of physical processes, this program supports basic and applied research in electronic materials, metals, glasses and ceramics, biological materials, combustion and fluids and chemicals. NASA facilities that provide weightless environments on the ground, in the air, and in space are available to U.S. and foreign investigators representing the academic and industrial communities. After a brief history of microgravity research, the text explains the advantages and methods of performing microgravity research. Illustrations follow of equipment used and experiments preformed aboard the Shuttle and of prospects for future research. The brochure concludes be describing the program goals and the opportunities for participation.

Geology orbiter comparison study

NASA Technical Reports Server (NTRS)

Cutts, J. A. J.; Blasius, K. R.; Davis, D. R.; Pang, K. D.; Shreve, D. C.

1977-01-01

Instrument requirements of planetary geology orbiters were examined with the objective of determining the feasibility of applying standard instrument designs to a host of terrestrial targets. Within the basic discipline area of geochemistry, gamma-ray, X-ray fluorescence, and atomic spectroscopy remote sensing techniques were considered. Within the discipline area of geophysics, the complementary techniques of gravimetry and radar were studied. Experiments using these techniques were analyzed for comparison at the Moon, Mercury, Mars and the Galilean satellites. On the basis of these comparative assessments, the adaptability of each sensing technique was judged as a basic technique for many targets, as a single instrument applied to many targets, as a single instrument used in different mission modes, and as an instrument capability for nongeoscience objectives.

Quantum dots in bio-imaging: Revolution by the small

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

Arya, Harinder; Kaul, Zeenia; Wadhwa, Renu

2005-04-22

Visual analysis of biomolecules is an integral avenue of basic and applied biological research. It has been widely carried out by tagging of nucleotides and proteins with traditional fluorophores that are limited in their application by features such as photobleaching, spectral overlaps, and operational difficulties. Quantum dots (QDs) are emerging as a superior alternative and are poised to change the world of bio-imaging and further its applications in basic and applied biology. The interdisciplinary field of nanobiotechnology is experiencing a revolution and QDs as an enabling technology have become a harbinger of this hybrid field. Within a decade, research onmore » QDs has evolved from being a pure science subject to the one with high-end commercial applications.« less

Mutation of the NPM1 gene contributes to the development of donor cell-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia.

PubMed

Rodríguez-Macías, Gabriela; Martínez-Laperche, Carolina; Gayoso, Jorge; Noriega, Víctor; Serrano, David; Balsalobre, Pascual; Muñoz-Martínez, Cristina; Díez-Martín, José L; Buño, Ismael

2013-08-01

Donor cell leukemia (DCL) is a rare but severe complication after allogeneic stem cell transplantation. Its true incidence is unknown because of a lack of correct recognition and reporting, although improvements in molecular analysis of donor-host chimerism are contributing to a better diagnosis of this complication. The mechanisms of leukemogenesis are unclear, and multiple factors can contribute to the development of DCL. In recent years, cord blood has emerged as an alternative source of hematopoietic progenitor cells, and at least 12 cases of DCL have been reported after unrelated cord blood transplantation. We report a new case of DCL after unrelated cord blood transplantation in a 44-year-old woman diagnosed as having acute lymphoblastic leukemia with t(1;19) that developed acute myeloid leukemia with normal karyotype and nucleophosmin (NPM1) mutation in donor cells. To our knowledge, this is the first report of NPM1 mutation contributing to DCL development. Copyright © 2013 Elsevier Inc. All rights reserved.

The super elongation complex (SEC) and MLL in development and disease

PubMed Central

Smith, Edwin; Lin, Chengqi; Shilatifard, Ali

2011-01-01

Transcriptional regulation at the level of elongation is vital for the control of gene expression and metazoan development. The mixed lineage leukemia (MLL) protein and its Drosophila homolog, Trithorax, which exist within COMPASS (complex of proteins associated with Set1)-like complexes, are master regulators of development. They are required for proper homeotic gene expression, in part through methylation of histone H3 on Lys 4. In humans, the MLL gene is involved in a large number of chromosomal translocations that create chimeric proteins, fusing the N terminus of MLL to several proteins that share little sequence similarity. Several frequent translocation partners of MLL were found recently to coexist in a super elongation complex (SEC) that includes known transcription elongation factors such as eleven-nineteen lysine-rich leukemia (ELL) and P-TEFb. Importantly, the SEC is required for HOX gene expression in leukemic cells, suggesting that chromosomal translocations involving MLL could lead to the overexpression of HOX and other genes through the involvement of the SEC. Here, we review the normal developmental roles of MLL and the SEC, and how MLL fusion proteins can mediate leukemogenesis. PMID:21460034

TAM Receptors in Leukemia: Expression, Signaling, and Therapeutic Implications

PubMed Central

Brandão, Luis; Migdall-Wilson, Justine; Eisenman, Kristen; Graham, Douglas K.

2016-01-01

In the past 30 years there has been remarkable progress in the treatment of leukemia and lymphoma. However, current treatments are largely ineffective against relapsed leukemia and, in the case of pediatric patients, are often associated with severe long-term toxicities. Thus, there continues to be a critical need for the development of effective biologically targeted therapies. The TAM family of receptor tyrosine kinases—Tyro3, Axl, and Mer—plays an important role in normal hematopoiesis, including natural killer cell maturation, macrophage function, and platelet activation and signaling. Furthermore, TAM receptor activation leads to upregulation of pro-survival and proliferation signaling pathways, and aberrant TAM receptor expression contributes to cancer development, including myeloid and lymphoid leukemia. This review summarizes the role of TAM receptors in leukemia. We outline TAM receptor expression patterns in different forms of leukemia, describe potential mechanisms leading to their overexpression, and delineate the signaling pathways downstream of receptor activation that have been implicated in leukemogenesis. Finally, we discuss the current research focused on inhibitors against these receptors in an effort to develop new therapeutic strategies for leukemia. PMID:22150307

Overexpression of Hiwi Inhibits the Cell Growth of Chronic Myeloid Leukemia K562 Cells and Enhances Their Chemosensitivity to Daunomycin.

PubMed

Wang, Yalin; Jiang, Yan; Bian, Cuicui; Dong, Yi; Ma, Chao; Hu, Xiaolin; Liu, Ziling

2015-09-01

Chronic myeloid leukemia (CML) is a clonal disorder characterized by excessive accumulation of myeloid cells in the peripheral blood. In the present study, to investigate the role of Hiwi in leukemogenesis, lentivirus-mediated Hiwi overexpression was performed in a CML cell line, K562 cells. Our data revealed that Hiwi protein expression was undetectable in K562 cells, and its overexpression suppressed cell proliferation, induced cell cycle arrest at G0/G1 and G2/M phases, and promoted apoptosis in K562 cells in vitro. Expression of anti-apoptotic protein, Bcl-2, was decreased in cells expressing Hiwi, whereas that of pro-apoptotic proteins, Bax, activated caspase-3, -9, and cleaved poly (ADP-ribose) polymerase were increased. Additionally, Hiwi upregulation enhanced the chemosensitivity of CML cells to daunomycin. Our study illustrates that expression deletion of Hiwi may be involved in the pathogenesis of human CML and suggests a possible role of Hiwi in regulating the cell growth, cell cycle, and apoptosis of CML cells in vitro.

Concise review: genetic dissection of hypoxia signaling pathways in normal and leukemic stem cells.

PubMed

Gezer, Deniz; Vukovic, Milica; Soga, Tomoyoshi; Pollard, Patrick J; Kranc, Kamil R

2014-06-01

Adult hematopoiesis depends on rare multipotent hematopoietic stem cells (HSCs) that self-renew and give rise to progenitor cells, which differentiate to all blood lineages. The strict regulation of the fine balance between self-renewal and differentiation is essential for normal hematopoiesis and suppression of leukemia development. HSCs and progenitor cells are commonly assumed to reside within the hypoxic BM microenvironment, however, there is no direct evidence supporting this notion. Nevertheless, HSCs and progenitors do exhibit a hypoxic profile and strongly express Hif-1α. Although hypoxia signaling pathways are thought to play important roles in adult HSC maintenance and leukemogenesis, the precise function of Hif-dependent signaling in HSCs remains to be uncovered. Here we discuss recent gain-of-function and loss-of-function studies that shed light on the complex roles of hypoxia-signaling pathways in HSCs and their niches in normal and malignant hematopoiesis. Importantly, we comment on the current and often contrasting interpretations of the role of Hif-dependent signaling in stem cell functions. © 2014 AlphaMed Press.

The non-coding RNA landscape of human hematopoiesis and leukemia.

PubMed

Schwarzer, Adrian; Emmrich, Stephan; Schmidt, Franziska; Beck, Dominik; Ng, Michelle; Reimer, Christina; Adams, Felix Ferdinand; Grasedieck, Sarah; Witte, Damian; Käbler, Sebastian; Wong, Jason W H; Shah, Anushi; Huang, Yizhou; Jammal, Razan; Maroz, Aliaksandra; Jongen-Lavrencic, Mojca; Schambach, Axel; Kuchenbauer, Florian; Pimanda, John E; Reinhardt, Dirk; Heckl, Dirk; Klusmann, Jan-Henning

2017-08-09

Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis. Following the incorporation of acute myeloid leukemia samples into the landscape, we further uncover prognostically relevant non-coding RNA stem cell signatures shared between acute myeloid leukemia blasts and healthy hematopoietic stem cells. Our findings highlight the importance of the non-coding transcriptome in the formation and maintenance of the human blood hierarchy.While micro-RNAs are known regulators of haematopoiesis and leukemogenesis, the role of long non-coding RNAs is less clear. Here the authors provide a non-coding RNA expression landscape of the human hematopoietic system, highlighting their role in the formation and maintenance of the human blood hierarchy.

miR-137 downregulates c-kit expression in acute myeloid leukemia.

PubMed

Hu, Yanping; Dong, Xiaolong; Chu, Guoming; Lai, Guangrui; Zhang, Bijun; Wang, Leitong; Zhao, Yanyan

2017-06-01

The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial. The aim of this work was to verify whether miR-137 targets c-kit and to research the biological effects of restoring miR-137 expression in leukemia cells. We found that miR-137 binds specifically to the 3'-UTR of c-kit and suppresses the expression and activities of c-kit. There is a negative correlation between miR-137 and c-kit expression in both patients and cell lines determined by screening large clinical samples. We found that miR-137 can inhibit proliferation, promote apoptosis, and induce differentiation of c-kit+ AML cells. We determined that miR-137 can participate in the leukemogenesis by regulating c-kit, which could be used as a therapeutic target for acute myeloid leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

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

Tress, E.; Pierotti, M.; DeLeo, A.B.

1982-02-01

To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instancesmore » a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia.« less

The role of methylenetetrahydrofolate reductase in acute lymphoblastic leukemia in a Brazilian mixed population.

PubMed

Zanrosso, Crisiane Wais; Hatagima, Ana; Emerenciano, Mariana; Ramos, Flávio; Figueiredo, Alexandre; Félix, Têmis Maria; Segal, Sandra L; Giugliani, Roberto; Guigliani, Roberto; Muniz, Maria Tereza Cartaxo; Pombo-de-Oliveira, Maria S

2006-04-01

The polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with leukemogenesis. In order to investigate the influence of two polymorphisms in the MTHFR gene, 677C>T and 1298A>C, on the risk of acute lymphoblastic leukemia (ALL) we performed a case-control study in children from different Brazilians' regions. Genotyping of 176 ALL and 199 unselected healthy subjects was performed using PCR-RFLP assay. There was no association between the 677C>T or 1298A>C and risk of ALL in total case-control sample. However, 677T allele was linked to a decrease risk of ALL [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.22-0.86], whereas the 1298A>C polymorphism presents an elevated risk factor [OR, 2.01; 95% CI, 1.01-3.99] in non-White children. Our investigation provides interesting data concerning the opposite effect of A1298C polymorphisms, particularly in the light of relatively scarce data regarding the MTHFR role in leukemia susceptibility in different populations.

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

PubMed Central

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E.

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance. PMID:24740120

Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

PubMed

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Concise review: preleukemic stem cells: molecular biology and clinical implications of the precursors to leukemia stem cells.

PubMed

Pandolfi, Ashley; Barreyro, Laura; Steidl, Ulrich

2013-02-01

Recent experimental evidence has shown that acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from transformed immature hematopoietic cells following the accumulation of multiple stepwise genetic and epigenetic changes in hematopoietic stem cells and committed progenitors. The series of transforming events initially gives rise to preleukemic stem cells (pre-LSC), preceding the formation of fully transformed leukemia stem cells (LSC). Despite the established use of poly-chemotherapy, relapse continues to be the most common cause of death in AML and MDS. The therapeutic elimination of all LSC, as well as pre-LSC, which provide a silent reservoir for the re-formation of LSC, will be essential for achieving lasting cures. Conventional sequencing and next-generation genome sequencing have allowed us to describe many of the recurrent mutations in the bulk cell populations in AML and MDS, and recent work has also focused on identifying the initial molecular changes contributing to leukemogenesis. Here we review recent and ongoing advances in understanding the roles of pre-LSC, and the aberrations that lead to pre-LSC formation and subsequent LSC transformation.

Involvement of MicroRNA in T-Cell Differentiation and Malignancy

PubMed Central

Saki, Najmaldin; Soleimani, Masoud; Hajizamani, Saeideh; Shahjahani, Mohammad; Kast, Richard E.; Mortazavi, Yousef

2015-01-01

ABSTRACT MicroRNAs are 19–22 nucleotide RNAs involved in such important processes as development, proliferation, differentiation and apoptosis. Different miRNAs are uniquely expressed in lymphoid T cells, and play a role indevelopment and differentiation of various subtypes by targeting their target genes. Recent studies have shown that aberrant miRNA expression may be involved in T cell leukemogenesis and lymphogenesis, and may function as tumor suppressor (such as miR-451, miR-31, miR-150, and miR-29a) or oncogene (e.g. miR-222, miR-223, miR-17-92, miR-155). MiRNAs can be used as new biomarkers for prognosis and diagnosis or as an index of disease severity in T-cell leukemia and lymphoma. This article presents a review of studies in recent years on the role of miRNAs in T-cell development and their aberrant expression in pathogenesis of T-cell leukemia and lymphoma. Characterizing miRNAs can help recognize their role as new important molecules with prognostic and therapeutic applications. PMID:25802699

Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia

PubMed Central

2013-01-01

Background The predominant mechanism by which human tumors maintain telomere length is via telomerase. In ~10% of tumor samples, however, telomere length is conserved, despite no detectable telomerase activity, in part through activation of the alternative lengthening of telomeres (ALT) pathway. Methods We studied the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic phase (CP). Results We identified the presence of ECTR in primary leukemia cells from some of these samples, which indicates the possible involvement of an ALT mechanism. Moreover, we found that some samples exhibited both circular ECTR and telomerase activities, suggesting that both mechanisms can contribute to the onset of CML. Conclusion We propose that ALT or the combined activities of ALT and telomerase might be required for the early stages of leukemogenesis. These findings shed new light into the oncogenic pathways responsible for the maintenance of telomere length in leukemia, which will ultimately determine the effectiveness of anti-telomerase-based treatment protocols. PMID:23547895

Lateral Attenuation of Aircraft Flight Noise.

DTIC Science & Technology

1985-03-01

levels with elevation angle. Comparisons of different Imodels are made in terms of the differences in A - levels for a flyover with the observer directly...attenuation adjustment to be applied to the basic noise data is the same when applied to maximum levels (maximum A - levels for example) or to integrated...attenuation values were applied to sets of one-third octave band spectra for different aircraft The resulting differences in A - levels for these noise spectra

[Basic science and applied science].

PubMed

Pérez-Tamayo, R

2001-01-01

A lecture was presented by the author at the Democratic Opinion Forum on Health Teaching and Research, organized by Mexico's National Health Institutes Coordinating Office, at National Cardiology Institute "Ignacio Chavez", where he presented a critical review of the conventional classification of basic and applied science, as well as his personal view on health science teaching and research. According to the author, "well-conducted science" is that "generating reality-checked knowledge" and "mis-conducted science" is that "unproductive or producing 'just lies' and 'non-fundable'. To support his views, the author reviews utilitarian and pejorative definitions of science, as well as those of committed and pure science, useful and useless science, and practical and esoterical science, as synonyms of applied and basic science. He also asserts that, in Mexico, "this classification has been used in the past to justify federal funding cutbacks to basic science, allegedly because it is not targeted at solving 'national problems' or because it was not relevant to priorities set in a given six-year political administration period". Regarding health education and research, the author asserts that the current academic programs are inefficient and ineffective; his proposal to tackle these problems is to carry out a solid scientific study, conducted by a multidisciplinary team of experts, "to design the scientific researcher curricula from recruitment of intelligent young people to retirement or death". Performance assessment of researchers would not be restricted to publication of papers, since "the quality of scientific work and contribution to the development of science is not reflected by the number of published papers". The English version of this paper is available at: http://www.insp.mx/salud/index.html

Research, the lifeline of medicine.

PubMed

Kornberg, A

1976-05-27

Advances in medicine spring from discoveries in physics, chemistry and biology. Among key contributions to the diagnosis, treatment and prevention of cardiovascular and pulmonary diseases, a recent Comroe-Dripps analysis shows two thirds to have been basic rather than applied research. Without a firm foundation in basic knowledge innovations perceived as advances prove hollow and collapse. Strong social, economic and political pressures now threaten acquisition of basic knowledge. Scientists feel driven to undertake excessively complex problems and gamble against the historical record that science generally progresses by tackling discrete and well defined questions. Regardless of circumstances, professional standards require the physician and scientist to be creative and enlarge the fund of knowledge.

Facies Interpretation and the Stratigraphic Record

NASA Astrophysics Data System (ADS)

Cisne, John

This book is a short, readable, and interesting introduction to facies analysis—or as Hallam prefers to call it, facies interpretation—in the form of an advanced undergraduate to beginning graduate level textbook. Unlike conventional textbooks on the subject, the emphasis here is not so much on the basics of sedimentation and stratigraphy as on applying the basics to sweeping, large-scale problems in tectonics, paleo-oceanography, paleoclimatology, and the history of life. This is not a comprehensive textbook. One must know the basics to appreciate it fully. But its very brevity and portability combine with its extensive bibliography to make it a particularly useful guide to recent work.

Research and technology, fiscal year 1983

NASA Technical Reports Server (NTRS)

1983-01-01

The responibilities and programs of the Goddard Space Flight Center are ranged from basic research in the space and Earth sciences through the management of numerous flight projects to operational responsibility for the tracking of and data acquisition from NASA's Earth orbiting satellites, Progress in the areas of spacecraft technology, sensor development and data system development, as well as in the basic and applied to research in the space and Earth sciences that they support is highlighted.

Applied Problems and Use of Technology in an Aligned Way in Basic Courses in Probability and Statistics for Engineering Students--A Way to Enhance Understanding and Increase Motivation

ERIC Educational Resources Information Center

Zetterqvist, Lena

2017-01-01

Researchers and teachers often recommend motivating exercises and use of mathematics or statistics software for the teaching of basic courses in probability and statistics. Our courses are given to large groups of engineering students at Lund Institute of Technology. We found that the mere existence of real-life data and technology in a course…

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

Milnes, M.; Baylor, L.C.; Bave, S.

This article offers a basic review of fiber-optic sensing technology, or more specifically, fiber-optic sensing technology as applied to the qualitative or quantitative identification of a chemical sample, and how it works,

Unit Cohesion and the Surface Navy: Does Cohesion Affect Performance

DTIC Science & Technology

1989-12-01

v. 68, 1968. Neter, J., Wasserman, W., and Kutner, M. H., Applied Linear Regression Models, 2d ed., Boston, MA: Irwin, 1989. Rand Corporation R-2607...Neter, J., Wasserman, W., and Kutner, M. H., Applied Linear Regression Models, 2d ed., Boston, MA: Irwin, 1989. SAS User’s Guide: Basics, Version 5 ed

Progressive-Ratio Schedules and Applied Behavior Analysis

ERIC Educational Resources Information Center

Poling, Alan

2010-01-01

Establishing appropriate relations between the basic and applied areas of behavior analysis has been of long and persistent interest to the author. In this article, the author illustrates that there is a direct relation between how hard an organism will work for access to an object or activity, as indexed by the largest ratio completed under a…

20 CFR 10.6 - What special statutory definitions apply to dependents and survivors?

Code of Federal Regulations, 2012 CFR

2012-04-01

... basic benefit augmented at a specified rate for certain persons who live in the beneficiary's household... benefit or an augmented benefit, apply to the provisions of this part but not to the death gratuity... necessary to qualify as a beneficiary for a death gratuity benefit as well as allowing half the death...

20 CFR 10.6 - What special statutory definitions apply to dependents and survivors?

Code of Federal Regulations, 2014 CFR

2014-04-01

... basic benefit augmented at a specified rate for certain persons who live in the beneficiary's household... benefit or an augmented benefit, apply to the provisions of this part but not to the death gratuity... necessary to qualify as a beneficiary for a death gratuity benefit as well as allowing half the death...

20 CFR 10.6 - What special statutory definitions apply to dependents and survivors?

Code of Federal Regulations, 2013 CFR

2013-04-01

... basic benefit augmented at a specified rate for certain persons who live in the beneficiary's household... benefit or an augmented benefit, apply to the provisions of this part but not to the death gratuity... necessary to qualify as a beneficiary for a death gratuity benefit as well as allowing half the death...

Employment Skills for the 21st Century: Applied Activities To Develop a Competitive American Workforce. Teacher Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This publication is a collection of 201 activities designed to give students practice in developing and applying in meaningful real-life settings both basic academic skills in reading, writing, and computation, and the more advanced higher-order skills of problem solving, critical thinking, group interaction, and oral communication. These…

21 CFR 1303.22 - Procedure for applying for individual manufacturing quotas.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacturing quotas. Any person who is registered to manufacture any basic class of controlled substance listed in Schedule I or II and who desires to manufacture a quantity of such class shall apply on DEA Form 189 for a manufacturing quota for such quantity of such class. Copies of DEA Form 189 may be obtained...

42 CFR 59a.1 - Programs to which these regulations apply.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Programs to which these regulations apply. 59a.1 Section 59a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL LIBRARY OF MEDICINE GRANTS Grants for Establishing, Expanding, and Improving Basic Resources § 59a.1...

42 CFR 59a.1 - Programs to which these regulations apply.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Programs to which these regulations apply. 59a.1 Section 59a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL LIBRARY OF MEDICINE GRANTS Grants for Establishing, Expanding, and Improving Basic Resources § 59a.1...

Group Training of Applied Behavior Analysis (ABA) Knowledge Competencies to Community-Based Service Providers for Adults with Developmental Disabilities

ERIC Educational Resources Information Center

Luiselli, James K.; St. Amand, CarrieAnne; MaGee, Christine; Sperry, James M.

2008-01-01

We describe a training program to teach applied behavior analysis (ABA) knowledge competencies to paraprofessional staff (N = 47) at a habilitation services agency for adults with developmental disabilities. Before and following training, staff completed assessment of knowledge tests for three content areas: basic learning principles,…

Evaluation on Compressive Characteristics of Medical Stents Applied by Mesh Structures

NASA Astrophysics Data System (ADS)

Hirayama, Kazuki; He, Jianmei

2017-11-01

There are concerns about strength reduction and fatigue fracture due to stress concentration in currently used medical stents. To address these problems, meshed stents applied by mesh structures were interested for achieving long life and high strength perfromance of medical stents. The purpose of this study is to design basic mesh shapes to obatin three dimensional (3D) meshed stent models for mechanical property evaluation. The influence of introduced design variables on compressive characteristics of meshed stent models are evaluated through finite element analysis using ANSYS Workbench code. From the analytical results, the compressive stiffness are changed periodically with compressive directions, average results need to be introduced as the mean value of compressive stiffness of meshed stents. Secondly, compressive flexibility of meshed stents can be improved by increasing the angle proportional to the arm length of the mesh basic shape. By increasing the number of basic mesh shapes arranged in stent’s circumferential direction, compressive rigidity of meshed stent tends to be increased. Finaly reducing the mesh line width is found effective to improve compressive flexibility of meshed stents.

Development of Independent-type Optical CT

NASA Astrophysics Data System (ADS)

Yamaguchi, Tatsushi; Shiozawa, Daigoro; Rokunohe, Toshiaki; Kida, Junzo; Zhang, Wei

Optical current transformers (optical CTs) have features that they can be made much smaller and lighter than conventional electromagnetic induction transformers by their simple structure, and contribute to improvement of equipment reliability because of their excellent surge resistance performance. Authors consider optical CTs to be next generation transformers, and are conducting research and development of optical CTs aiming to apply to measuring and protection in electric power systems. Specifically we developed an independent-type optical CT by utilizing basic data of optical CTs accumulated for large current characteristics, temperature characteristics, vibration resistance characteristics, and so on. In performance verification, type tests complying with IEC standards, such as short-time current tests, insulation tests, accuracy tests, and so on, showed good results. This report describes basic principle and configuration of optical CTs. After that, as basic characteristics of optical CTs, conditions and results of verification tests for dielectric breakdown characteristics of sensor fibers, large current characteristics, temperature characteristics, and vibration resistance characteristics are described. Finally, development outline of the independent-type optical CT aiming to apply to all digital substation and its type tests results are described.

Fair shares: a preliminary framework and case analyzing the ethics of offshoring.

PubMed

Gordon, Cameron; Zimmerman, Alan

2010-06-01

Much has been written about the offshoring phenomenon from an economic efficiency perspective. Most authors have attempted to measure the net economic effects of the strategy and many purport to show that "in the long run" that benefits will outweigh the costs. There is also a relatively large literature on implementation which describes the best way to manage the offshoring process. But what is the morality of offshoring? What is its "rightness" or "wrongness?" Little analysis of the ethics of offshoring has been completed thus far. This paper develops a preliminary framework for analyzing the ethics of offshoring and then applies this framework to basic case study of offshoring in the U.S. The paper following discusses the definition of offshoring; shifts to the basic philosophical grounding of the ethical concepts; develops a template for conducting an ethics analysis of offshoring; applies this template using basic data for offshoring in the United States; and conducts a preliminary ethical analysis of the phenomenon in that country, using a form of utilitarianism as an analytical baseline. The paper concludes with suggestions for further research.

Spectral-element simulations of wave propagation in complex exploration-industry models: Imaging and adjoint tomography

NASA Astrophysics Data System (ADS)

Luo, Y.; Nissen-Meyer, T.; Morency, C.; Tromp, J.

2008-12-01

Seismic imaging in the exploration industry is often based upon ray-theoretical migration techniques (e.g., Kirchhoff) or other ideas which neglect some fraction of the seismic wavefield (e.g., wavefield continuation for acoustic-wave first arrivals) in the inversion process. In a companion paper we discuss the possibility of solving the full physical forward problem (i.e., including visco- and poroelastic, anisotropic media) using the spectral-element method. With such a tool at hand, we can readily apply the adjoint method to tomographic inversions, i.e., iteratively improving an initial 3D background model to fit the data. In the context of this inversion process, we draw connections between kernels in adjoint tomography and basic imaging principles in migration. We show that the images obtained by migration are nothing but particular kinds of adjoint kernels (mainly density kernels). Migration is basically a first step in the iterative inversion process of adjoint tomography. We apply the approach to basic 2D problems involving layered structures, overthrusting faults, topography, salt domes, and poroelastic regions.

Analysis of the interaction between experimental and applied behavior analysis.

PubMed

Virues-Ortega, Javier; Hurtado-Parrado, Camilo; Cox, Alison D; Pear, Joseph J

2014-01-01

To study the influences between basic and applied research in behavior analysis, we analyzed the coauthorship interactions of authors who published in JABA and JEAB from 1980 to 2010. We paid particular attention to authors who published in both JABA and JEAB (dual authors) as potential agents of cross-field interactions. We present a comprehensive analysis of dual authors' coauthorship interactions using social networks methodology and key word analysis. The number of dual authors more than doubled (26 to 67) and their productivity tripled (7% to 26% of JABA and JEAB articles) between 1980 and 2010. Dual authors stood out in terms of number of collaborators, number of publications, and ability to interact with multiple groups within the field. The steady increase in JEAB and JABA interactions through coauthors and the increasing range of topics covered by dual authors provide a basis for optimism regarding the progressive integration of basic and applied behavior analysis. © Society for the Experimental Analysis of Behavior.

Permissive Sense and Antisense Transcription from the 5′ and 3′ Long Terminal Repeats of Human T-Cell Leukemia Virus Type 1

PubMed Central

Polakowski, Nicholas; Hoang, Kimson

2016-01-01

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus, and, as such, its genome becomes chromosomally integrated following infection. The resulting provirus contains identical 5′ and 3′ peripheral long terminal repeats (LTRs) containing bidirectional promoters. Antisense transcription from the 3′ LTR regulates expression of a single gene, hbz, while sense transcription from the 5′ LTR controls expression of all other viral genes, including tax. Both the HBZ and Tax proteins are implicated in the development of adult T-cell leukemia (ATL), a T-cell malignancy caused by HTLV-1 infection. However, these proteins appear to harbor opposing molecular functions, indicating that they may act independently and at different time points prior to leukemogenesis. Here, we used bidirectional reporter constructs to test whether transcriptional interference serves as a mechanism that inhibits simultaneous expression of Tax and HBZ. We found that sense transcription did not interfere with antisense transcription from the 3′ LTR and vice versa, even with strong transcription emanating from the opposing direction. Therefore, bidirectional transcription across the provirus might not restrict hbz or tax expression. Single-cell analyses revealed that antisense transcription predominates in the absence of Tax, which transactivates viral sense transcription. Interestingly, a population of Tax-expressing cells exhibited antisense but not activated sense transcription. Consistent with the ability of Tax to induce cell cycle arrest, this population was arrested in G0/G1 phase. These results imply that cell cycle arrest inhibits Tax-mediated activation of sense transcription without affecting antisense transcription, which may be important for long-term viral latency. IMPORTANCE The chromosomally integrated form of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) contains identical DNA sequences, known as long terminal repeats (LTRs), at its 5′ and 3′ ends. The LTRs modulate transcription in both forward (sense) and reverse (antisense) directions. We found that sense transcription from the 5′ LTR does not interfere with antisense transcription from the 3′ LTR, allowing viral genes encoded on opposite DNA strands to be simultaneously transcribed. Two such genes are tax and hbz, and while they are thought to function at different times during the course of infection to promote leukemogenesis of infected T cells, our results indicate that they can be simultaneously transcribed. We also found that the ability of Tax to induce cell cycle arrest inhibits its fundamental function of activating viral sense transcription but does not affect antisense transcription. This regulatory mechanism may be important for long-term HTLV-1 infection. PMID:26792732

77 FR 64800 - Secretary of Energy Advisory Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... reestablished to provide advice and recommendations to the Secretary on the Department's basic and applied research, economic and national security policy, educational issues, operational issues and other...

Structural Biology and Molecular Applications Research

Cancer.gov

Part of NCI's Division of Cancer Biology's research portfolio, research and development in this area focuses on enabling technologies, models, and methodologies to support basic and applied cancer research.

48 CFR 1834.201 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

.../project manager. (iv) EVM is not required on contracts for non-developmental engineering support services, steady state operations, basic and applied research, and routine services such as janitorial services or...

Anthology of the Development of Radiation Transport Tools as Applied to Single Event Effects

NASA Astrophysics Data System (ADS)

Reed, R. A.; Weller, R. A.; Akkerman, A.; Barak, J.; Culpepper, W.; Duzellier, S.; Foster, C.; Gaillardin, M.; Hubert, G.; Jordan, T.; Jun, I.; Koontz, S.; Lei, F.; McNulty, P.; Mendenhall, M. H.; Murat, M.; Nieminen, P.; O'Neill, P.; Raine, M.; Reddell, B.; Saigné, F.; Santin, G.; Sihver, L.; Tang, H. H. K.; Truscott, P. R.; Wrobel, F.

2013-06-01

This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing websites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools.

A Keyboard for Underwater Performance Assessment Battery Testing

DTIC Science & Technology

1990-11-08

Applied Engineering . This four button underwater keyboard uses only a small portion of the boards capacity. The cable is connected to the I/O 32 board via a...H.O., by Applied Engineering ) require special programming to work with the IO 32 board. If the boards are accessed directly from Apple Basic with the... Applied Engineering , 1988) is presented in the Appendix. This program will work with either the enhanced or the unenhanced version of the Apple lie. 6

Water Resources Research October 1, 1979 - September 30, 1980: Summary statements of research activities by the Water Resources Division

USGS Publications Warehouse

,

1981-01-01

Research in the WRD had its beginnings in the late 1950's when the "core research" line item was added to the Congressional budget. Since this time the Federal program has grown from a "basic sciences" program to one that includes a broad spectrum of basic and applied scientific investigations. Water resources research in WRD includes the study of water in all its phases and uses the basic sciences of mathematics, chemistry, physics, biology, geology and engineering to gain a fundamental understanding of the processes that affect the movement of water and its chemical constituents through hydrologic systems. The basic knowledge and methodologies derived from water resources research are applicable not only to the solution of current problems associated with the Nation's water resources, but also to anticipated hydrologic issues.

Basic firefly algorithm for document clustering

NASA Astrophysics Data System (ADS)

Mohammed, Athraa Jasim; Yusof, Yuhanis; Husni, Husniza

2015-12-01

The Document clustering plays significant role in Information Retrieval (IR) where it organizes documents prior to the retrieval process. To date, various clustering algorithms have been proposed and this includes the K-means and Particle Swarm Optimization. Even though these algorithms have been widely applied in many disciplines due to its simplicity, such an approach tends to be trapped in a local minimum during its search for an optimal solution. To address the shortcoming, this paper proposes a Basic Firefly (Basic FA) algorithm to cluster text documents. The algorithm employs the Average Distance to Document Centroid (ADDC) as the objective function of the search. Experiments utilizing the proposed algorithm were conducted on the 20Newsgroups benchmark dataset. Results demonstrate that the Basic FA generates a more robust and compact clusters than the ones produced by K-means and Particle Swarm Optimization (PSO).

Representation of the quantum Fourier transform on multilevel basic elements by a sequence of selective rotation operators

NASA Astrophysics Data System (ADS)

Ermilov, A. S.; Zobov, V. E.

2007-12-01

To experimentally realize quantum computations on d-level basic elements (qudits) at d > 2, it is necessary to develop schemes for the technical realization of elementary logical operators. We have found sequences of selective rotation operators that represent the operators of the quantum Fourier transform (Walsh-Hadamard matrices) for d = 3-10. For the prime numbers 3, 5, and 7, the well-known method of linear algebra is applied, whereas, for the factorable numbers 6, 9, and 10, the representation of virtual spins is used (which we previously applied for d = 4, 8). Selective rotations can be realized, for example, by means of pulses of an RF magnetic field for systems of quadrupole nuclei or laser pulses for atoms and ions in traps.

Combining cationic and anionic mixed-mode sorbents in a single cartridge to extract basic and acidic pharmaceuticals simultaneously from environmental waters.

PubMed

Salas, Daniela; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa Maria

2018-01-01

The aim of the present study is to broaden the applications of mixed-mode ion-exchange solid-phase extraction sorbents to extract both basic and acidic compounds simultaneously by combining the sorbents in a single cartridge and developing a simplified extraction procedure. Four different cartridges containing negative and positive charges in the same configuration were evaluated and compared to extract a group of basic, neutral, and acidic pharmaceuticals selected as model compounds. After a thorough optimization of the extraction conditions, the four different cartridges showed to be capable of retaining basic and acidic pharmaceuticals simultaneously through ionic interactions, allowing the introduction of a washing step with 15 mL methanol to eliminate interferences retained by hydrophobic interactions. Using the best combined cartridge, a method was developed, validated, and further applied to environmental waters to demonstrate that the method is promising for the extraction of basic and acidic compounds from very complex samples.

Basics of elder law and legal liabilities of negligence and malpractice for physicians as they apply to individuals with disabilities.

PubMed

Ullman, David; Zuller, Michael E

2005-02-01

This article provides information regarding the issues that physicians face when dealing with elderly patients with cognitive deficits. It includes a discussion of basic legal terms and concepts that medical personnel should understand, various difficulties encountered by patients and families in crisis situations, and how the legal system deals with these issues. It concludes with a general discussion of the legal liabilities of negligence and malpractice.

48 CFR 31.001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... four areas: (a) basic research, (b) applied research, (c) development, and (d) systems and other... the plan. Independent research and development (IR&D) cost means the cost of effort which is neither...

48 CFR 6.102 - Use of competitive procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... procedure (see subpart 36.6 for procedures). (2) Competitive selection of basic and applied research and... nature identifying areas of research interest, including criteria for selecting proposals, and soliciting...

Advancing the Science of ISRU

NASA Astrophysics Data System (ADS)

Gertsch, L. S.; Morris, K. A.

2017-02-01

The sustainable exploration of space requires in situ resource utilization (ISRU). Successful ISRU depends on a solid science foundation; consequently, planetary science must include basic and applied science investigations to support ISRU.

The Evolution of Vocational Psychology: Questions for a Postmodern Applied Discipline

ERIC Educational Resources Information Center

Krieshok, Thomas S.; Motl, Thomas C.; Rutt, Benjamin T.

2011-01-01

Vocational psychology has a long history of acting as a lens that focuses research in basic sciences on the particular experience of work in people's lives. This article presents several areas on the ascendancy in the broader scientific literature and ask how vocational psychology might apply them to issues of work in people's lives. The authors'…

Automotive Mechanics as Applied to Auto Body; Auto Body Repair and Refinishing 3: 9037.02.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

This is a course in which the student will receive the general information, technical knowledge, basic skills, attitudes, and values required for job entry level as an auto body repair helper. Course content includes general and specific goals, orientation, instruction in service tools and bench skills, and auto mechanics as applied to auto body.…

PHONICS WITH CONTEXT CLUES AS APPLIED TO LANGUAGE ARTS.

ERIC Educational Resources Information Center

GUFFEY, MARY DEMAREE

A SIMPLIFIED METHOD OF PHONICS UTILIZING THE GESTALT METHOD OF LEARNING IS PRESENTED. THE WORDS IN THIS COURSE IN PHONICS ARE TO BE TAUGHT AT A TIME DIFFERENT FROM THE READING CLASSES, BUT THE PRINCIPLES DEVELOPED ARE TO BE APPLIED WITHIN THE READING CLASSES. THE COURSE CAN BE USED WITH ANY BASIC TEXT AND STRESSES THE ABILITY OF CHILDREN TO…

Applied Linguistics Project: Student-Led Computer Assisted Research in High School EAL/EAP

ERIC Educational Resources Information Center

Bohát, Róbert; Rödlingová, Beata; Horáková, Nina

2015-01-01

The Applied Linguistics Project (ALP) started at the International School of Prague (ISP) in 2013. Every year, Grade 9 English as an Additional Language (EAL) students identify an area of learning in need of improvement and design a research method followed by data collection and analysis using basic computer software tools or online corpora.…

76 FR 55213 - Technical Amendments to Federal Employees' Retirement System; Present Value Conversion Factors...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

...) revising the factor at 5 CFR 843.309(b)(2) used to convert a lump sum basic employee death benefit under 5... would apply to deaths occurring on or after October 1, 2004. The revised factor, however, applies to deaths occurring on or after October 1, 2011. Therefore, this document corrects the final regulation by...

The method of averages applied to the KS differential equations

NASA Technical Reports Server (NTRS)

Graf, O. F., Jr.; Mueller, A. C.; Starke, S. E.

1977-01-01

A new approach for the solution of artificial satellite trajectory problems is proposed. The basic idea is to apply an analytical solution method (the method of averages) to an appropriate formulation of the orbital mechanics equations of motion (the KS-element differential equations). The result is a set of transformed equations of motion that are more amenable to numerical solution.

Recent developments in ejector technology in the Air Force: An overview

NASA Technical Reports Server (NTRS)

Nagaraja, K. S.

1979-01-01

Basic and applied studies in thrust augmentation conducted at the Aerospace Research Laboratory at Wright-Patterson AFB which led to an effective configuration of the jet flap diffuser ejector, are reviewed. A method for compressible ejector flow analysis, developed in support of the preliminary design of an ejector thrust aircraft, is discussed and applied to single- and two-stage ejectors.

The Impact of Cultural Capital on Secondary Student's Performance in Brazil

ERIC Educational Resources Information Center

Caprara, Bernardo

2016-01-01

The main goal of this study is to verify the effects of cultural capital on students' performance in an official test applied by the Brazilian government, as part of the National Assessment of Basic Education (Saeb). The data set used is from 2003 and involves 52,434 students. The standard test is applied every two years in the fields of…

Adlerian psychology as an intuitive operant system.

PubMed

Pratt, A B

1985-01-01

Traditional accounts of the Individual Psychology of Alfred Adler tend to sentimentalize his system and obscure its functional flavor. Six basic Adlerian positions on human behavior, including Rudolf Dreikurs' "four goals of misbehavior," are interpreted as a primitive statement of operant principles. Applied techniques long used by Individual Psychology practitioners strongly resemble interventions that applied behavior analysts have developed by more systematic means.

The State of Space Propulsion Research

NASA Technical Reports Server (NTRS)

Sackheim, R. L.; Cole, J. W.; Litchford, R. J.

2006-01-01

The current state of space propulsion research is assessed from both a historical perspective, spanning the decades since Apollo, and a forward-looking perspective, as defined by the enabling technologies required for a meaningful and sustainable human and robotic exploration program over the forthcoming decades. Previous research and technology investment approaches are examined and a course of action suggested for obtaining a more balanced portfolio of basic and applied research. The central recommendation is the establishment of a robust national Space Propulsion Research Initiative that would run parallel with systems development and include basic research activities. The basic framework and technical approach for this proposed initiative are defined and a potential implementation approach is recommended.

Tissue engineering and regenerative medicine in applied research: a year in review of 2014.

PubMed

Lin, Xunxun; Huang, Jia; Shi, Yuan; Liu, Wei

2015-04-01

Tissue engineering and regenerative medicine (TERM) remains to be one of the fastest growing fields, which covers a wide scope of topics of both basic and applied biological researches. This overview article summarized the advancements in applied researches of TERM area, including stem cell-mediated tissue regeneration, material science, and TERM clinical trial. These achievements demonstrated the great potential of clinical regenerative therapy of tissue/organ disease or defect through stem cells and tissue engineering approaches.

General In-Hole Procedures

EPA Pesticide Factsheets

The purpose of this section is to provide the basic information necessary to apply the most useful geophysical well logs for the solution of problems in groundwater, the environmental field, and for engineering applications.

48 CFR 2442.1107 - Contract clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... analytical nature (e.g., applied social science research); and (3) The contract requires the delivery of an overall end product (e.g., evaluation, study, model). (b) The Contracting Officer shall use the basic...

48 CFR 2442.1107 - Contract clause.

Code of Federal Regulations, 2012 CFR

2012-10-01

... analytical nature (e.g., applied social science research); and (3) The contract requires the delivery of an overall end product (e.g., evaluation, study, model). (b) The Contracting Officer shall use the basic...

48 CFR 2442.1107 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... analytical nature (e.g., applied social science research); and (3) The contract requires the delivery of an overall end product (e.g., evaluation, study, model). (b) The Contracting Officer shall use the basic...

48 CFR 9904.420-30 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... following three areas: (i) Basic and applied research, (ii) Development, and (iii) Systems and other concept... and a home office. (6) Independent research and development means the cost of effort which is neither...

A Primer of Human Development for Counselors.

ERIC Educational Resources Information Center

Hayes, Richard L.

1985-01-01

Presents the basic principles and dichotomies underlying human development theories and describe three contemporary approaches to human development: behaviorism, maturationism, and structuralism. Illustrates how different theories are applied to counseling practice. (MCF)

Memory: from the laboratory to everyday life.

PubMed

Schacter, Daniel L

2013-12-01

One of the key goals of memory research is to develop a basic understanding of the nature and characteristics of memory processes and systems. Another important goal is to develop useful applications of basic research to everyday life. This editorial considers two lines of work that illustrate some of the prospects for applying memory research to everyday life: interpolated quizzing to enhance learning in educational settings, and specificity training to enhance memory and associated functions in individuals who have difficulties remembering details of their past experiences.

GENERATING FRACTAL PATTERNS BY USING p-CIRCLE INVERSION

NASA Astrophysics Data System (ADS)

Ramírez, José L.; Rubiano, Gustavo N.; Zlobec, Borut Jurčič

2015-10-01

In this paper, we introduce the p-circle inversion which generalizes the classical inversion with respect to a circle (p = 2) and the taxicab inversion (p = 1). We study some basic properties and we also show the inversive images of some basic curves. We apply this new transformation to well-known fractals such as Sierpinski triangle, Koch curve, dragon curve, Fibonacci fractal, among others. Then we obtain new fractal patterns. Moreover, we generalize the method called circle inversion fractal be means of the p-circle inversion.

Electrowetting on polymer dispersed liquid crystal

NASA Astrophysics Data System (ADS)

Fan, Shih-Kang; Chiu, Cheng-Pu; Lin, Jing-Wei

2009-04-01

Polymer dispersed liquid crystal (PDLC) is used as a dielectric layer in electrowetting. By applying voltage between a liquid droplet and the electrode underlying PDLC, electrowetting occurs at the liquid/PDLC interface accompanied with electro-optic responses of the reoriented LC droplets embedded in PDLC. Two basic experiments investigating the electrowetting by sessile water droplets and the electro-optic effects through squeezed water droplets were design and performed. The basic functions of a liquid lens and droplet manipulations, including transporting, splitting, and merging, were demonstrated.

Ethics and managed care.

PubMed

Perkel, R L

1996-03-01

Managed care presents physicians with potential ethical dilemmas different from dilemmas in traditional fee-for-service practice. The ethical assumptions of managed care are explored, with special attention to the evolving dual responsibilities of physicians as patient advocates and as entrepreneurs. A number of proposals are described that delineate issues in support of and in opposition to managed care. Through an understanding of how to apply basic ethics principles to managed care participation, physicians may yet hold on to the basic ethic of the fiduciary doctor-patient relationship.

Basic and applied problems in developmental biology and immunobiology of cestode infections: Hymenolepis, Taenia and Echinococcus.

PubMed

Ito, A

2015-02-01

Differentiation and development of parasites, including longevity in host animals, are thought to be governed by host-parasite interactions. In this review, several topics on the developmental biology of cestode infections are discussed from immunobiological perspective with a focus on Hymenolepis, Taenia and Echinococcus infections. The basic premise of this review is that 'differentiation and development of cestodes' are somehow affected by host immune responses with an evolutionary history. © 2014 John Wiley & Sons Ltd.

A study about teaching quadratic functions using mathematical models and free software

NASA Astrophysics Data System (ADS)

Nepomucena, T. V.; da Silva, A. C.; Jardim, D. F.; da Silva, J. M.

2017-12-01

In the face of the reality of teaching Mathematics in Basic Education in Brazil, specially relating teach functions focusing their relevance to the student’s academic development in Basic and Superior Education, this work proposes the use of educational software to help the teaching of functions in Basic Education since the computers and software show as an outstanding option to help the teaching and learning processes. On the other hand, the study also proposes the use of Didactic Transposition as a methodology investigation and research. Along with this survey, some teaching interventions were applied to detect the main difficulties in the teaching process of functions in the Basic Education, analyzing the results obtained along the interventions in a qualitative form. Considering the discussion of the results at the end of the didactic interventions, it was verified that the results obtained were satisfactory.

Design of multiple representations e-learning resources based on a contextual approach for the basic physics course

NASA Astrophysics Data System (ADS)

Bakri, F.; Muliyati, D.

2018-05-01

This research aims to design e-learning resources with multiple representations based on a contextual approach for the Basic Physics Course. The research uses the research and development methods accordance Dick & Carey strategy. The development carried out in the digital laboratory of Physics Education Department, Mathematics and Science Faculty, Universitas Negeri Jakarta. The result of the process of product development with Dick & Carey strategy, have produced e-learning design of the Basic Physics Course is presented in multiple representations in contextual learning syntax. The appropriate of representation used in the design of learning basic physics include: concept map, video, figures, data tables of experiment results, charts of data tables, the verbal explanations, mathematical equations, problem and solutions example, and exercise. Multiple representations are presented in the form of contextual learning by stages: relating, experiencing, applying, transferring, and cooperating.

Brookhaven highlights: a two year report, July 1974--June 1976

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

Not Available

1976-01-01

Brief summaries are given of research activities in the areas of high energy physics, basic and applied energy science, and life sciences. Support activities and administrative data are also briefly reviewed.

Physics in the Ionosphere.

ERIC Educational Resources Information Center

Murket, A. J.

1979-01-01

Develops a simple model of radio wave propagation and illustrates how basic physical concepts such as refractive index, refraction, reflection and dispersion can be applied to a situation normally not met in introductory physics courses. (Author/GA)

Compact modeling of CRS devices based on ECM cells for memory, logic and neuromorphic applications.

PubMed

Linn, E; Menzel, S; Ferch, S; Waser, R

2013-09-27

Dynamic physics-based models of resistive switching devices are of great interest for the realization of complex circuits required for memory, logic and neuromorphic applications. Here, we apply such a model of an electrochemical metallization (ECM) cell to complementary resistive switches (CRSs), which are favorable devices to realize ultra-dense passive crossbar arrays. Since a CRS consists of two resistive switching devices, it is straightforward to apply the dynamic ECM model for CRS simulation with MATLAB and SPICE, enabling study of the device behavior in terms of sweep rate and series resistance variations. Furthermore, typical memory access operations as well as basic implication logic operations can be analyzed, revealing requirements for proper spike and level read operations. This basic understanding facilitates applications of massively parallel computing paradigms required for neuromorphic applications.

Working the truth and perfecting the moment for physicians and patients: a serious challenge for information systems.

PubMed

Garling, A C

1994-01-01

Most of us can remember the crowning sense of elegance we occasionally felt when we solved a very difficult geometry problem. We linked the proof to the postulates. It was almost like calling on history or the elders to stand silently with us in the flurry of our moment. We "worked truth." I'd like to capture a little of that same "working truth" and apply it in a very unlikely spot: information systems and information technology. It is time to go back and look at the basic postulates of knowledge and responsibility and truthfully apply them in the health care interchange between doctor and patient and make sure that our systems add to and even create an elegance so that the basic relationship of physician and patient in healing can flourish.

Improvement of Subsonic Basic Research Tunnel Flow Quality as Applied to Wall Mounted Testing

NASA Technical Reports Server (NTRS)

Howerton, Brian M.

1995-01-01

A survey to determine the characteristics of a boundary layer that forms on the wall of the Subsonic Basic Research Tunnel has been performed. Early results showed significant differences in the velocity profiles as measured spanwise across the wall. An investigation of the flow in the upstream contraction revealed the presence of a separation bubble at the beginning of the contraction which caused much of the observed unsteadiness. Vortex generators were successfully applied to the contraction inlet to alleviate the separation. A final survey of the wall boundary layer revealed variations in the displacement and momentum thicknesses to be less than +/- 5% for all but the most upper portion of the wall. The flow quality was deemed adequate to continue the planned follow-on tests to help develop the semi-span test technique.

Space human factors discipline science plan

NASA Technical Reports Server (NTRS)

1991-01-01

The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the comprehensive areas of behavior, performance, and human factors. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, defines critical questions in the subdiscipline areas, and identifies technological priorities. It covers the significant research areas critical to NASA's programmatic requirements for the Extended Duration Orbiter, Space Station Freedom, and Exploration mission science activities. These science activities include ground-based and flight; basic, applied and operational; and animal and human research and development. This document contains a general plan that will be used by both NASA Headquarters program offices and the field centers to review and plan basic, applied, and operational research and development activities, both intramural and extramural, in this area.

National Geospatial-Intelligence Agency Academic Research Program

NASA Astrophysics Data System (ADS)

Loomer, S. A.

2004-12-01

"Know the Earth.Show the Way." In fulfillment of its vision, the National Geospatial-Intelligence Agency (NGA) provides geospatial intelligence in all its forms and from whatever source-imagery, imagery intelligence, and geospatial data and information-to ensure the knowledge foundation for planning, decision, and action. To achieve this, NGA conducts a multi-disciplinary program of basic research in geospatial intelligence topics through grants and fellowships to the leading investigators, research universities, and colleges of the nation. This research provides the fundamental science support to NGA's applied and advanced research programs. The major components of the NGA Academic Research Program (NARP) are: - NGA University Research Initiatives (NURI): Three-year basic research grants awarded competitively to the best investigators across the US academic community. Topics are selected to provide the scientific basis for advanced and applied research in NGA core disciplines. - Historically Black College and University - Minority Institution Research Initiatives (HBCU-MI): Two-year basic research grants awarded competitively to the best investigators at Historically Black Colleges and Universities, and Minority Institutions across the US academic community. - Director of Central Intelligence Post-Doctoral Research Fellowships: Fellowships providing access to advanced research in science and technology applicable to the intelligence community's mission. The program provides a pool of researchers to support future intelligence community needs and develops long-term relationships with researchers as they move into career positions. This paper provides information about the NGA Academic Research Program, the projects it supports and how other researchers and institutions can apply for grants under the program.

Federal Funds for Research and Development: Fiscal Years 1983, 1984, and 1985. Volume XXXIII. Detailed Statistical Tables. Surveys of Science Resources Series.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC. Div. of Science Resources Studies.

Detailed statistical tables showing the funding levels of 92 federal agencies for research and development (R&D) are provided in this document. These tables are organized into the following sections: research, development, and R&D plant; R&D agency, character of work, and performer; total basic and applied applied research--agency,…

The Design and Development of a Context-Rich, Photo-Based Online Testing to Assess Students' Science Learning

ERIC Educational Resources Information Center

Lin, Min-Jin; Guo, Chorng-Jee; Hsu, Chia-Er

2011-01-01

This study designed and developed a CP-MCT (content-rich, photo-based multiple choice online test) to assess whether college students can apply the basic light concept to interpret daily light phenomena. One hundred college students volunteered to take the CP-MCT, and the results were statistically analyzed by applying t-test or ANOVA (Analysis of…

Does activity limitation predict discharge destination for postacute care patients?

PubMed

Chang, Feng-Hang; Ni, Pengsheng; Jette, Alan M

2014-09-01

This study aimed to examine the ability of different domains of activity limitation to predict discharge destination (home vs. nonhome settings) 1 mo after hospital discharge for postacute rehabilitation patients. A secondary analysis was conducted using a data set of 518 adults with neurologic, lower extremity orthopedic, and complex medical conditions followed after discharge from a hospital into postacute care. Variables collected at baseline include activity limitations (basic mobility, daily activity, and applied cognitive function, measured by the Activity Measure for Post-Acute Care), demographics, diagnosis, and cognitive status. The discharge destination was recorded at 1 mo after being discharged from the hospital. Correlational analyses revealed that the 1-mo discharge destination was correlated with two domains of activity (basic mobility and daily activity) and cognitive status. However, multiple logistic regression and receiver operating characteristic curve analyses showed that basic mobility functioning performed the best in discriminating home vs. nonhome living. This study supported the evidence that basic mobility functioning is a critical determinant of discharge home for postacute rehabilitation patients. The Activity Measure for Post-Acute Care-basic mobility showed good usability in discriminating home vs. nonhome living. The findings shed light on the importance of basic mobility functioning in the discharge planning process.

From basic to applied research to improve outcomes for individuals who require augmentative and alternative communication: potential contributions of eye tracking research methods.

PubMed

Light, Janice; McNaughton, David

2014-06-01

In order to improve outcomes for individuals who require AAC, there is an urgent need for research across the full spectrum--from basic research to investigate fundamental language and communication processes, to applied clinical research to test applications of this new knowledge in the real world. To date, there has been a notable lack of basic research in the AAC field to investigate the underlying cognitive, sensory perceptual, linguistic, and motor processes of individuals with complex communication needs. Eye tracking research technology provides a promising method for researchers to investigate some of the visual cognitive processes that underlie interaction via AAC. The eye tracking research technology automatically records the latency, duration, and sequence of visual fixations, providing key information on what elements attract the individual's attention (and which ones do not), for how long, and in what sequence. As illustrated by the papers in this special issue, this information can be used to improve the design of AAC systems, assessments, and interventions to better meet the needs of individuals with developmental and acquired disabilities who require AAC (e.g., individuals with autism spectrum disorders, Down syndrome, intellectual disabilities of unknown origin, aphasia).

Understanding the Thermodynamic Properties of the Elastocaloric Effect Through Experimentation and Modelling

NASA Astrophysics Data System (ADS)

Tušek, Jaka; Engelbrecht, Kurt; Mañosa, Lluis; Vives, Eduard; Pryds, Nini

2016-12-01

This paper presents direct and indirect methods for studying the elastocaloric effect (eCE) in shape memory materials and its comparison. The eCE can be characterized by the adiabatic temperature change or the isothermal entropy change (both as a function of applied stress/strain). To get these quantities, the evaluation of the eCE can be done using either direct methods, where one measures (adiabatic) temperature changes or indirect methods where one can measure the stress-strain-temperature characteristics of the materials and from these deduce the adiabatic temperature and isothermal entropy changes. The former can be done using the basic thermodynamic relations, i.e. Maxwell relation and Clausius-Clapeyron equation. This paper further presents basic thermodynamic properties of shape memory materials, such as the adiabatic temperature change, isothermal entropy change and total entropy-temperature diagrams (all as a function of temperature and applied stress/strain) of two groups of materials (Ni-Ti and Cu-Zn-Al alloys) obtained using indirect methods through phenomenological modelling and Maxwell relation. In the last part of the paper, the basic definition of the efficiency of the elastocaloric thermodynamic cycle (coefficient of performance) is defined and discussed.

The Tao of Microelectronics

NASA Astrophysics Data System (ADS)

Zhang, Yumin

2014-12-01

Microelectronics is a challenging course to many undergraduate students and is often described as very messy. Before taking this course, all the students have learned circuit analysis, where basically all the problems can be solved by applying Kirchhoff's laws. In addition, most engineering students have also learned engineering mechanics: statics and dynamics, where Newton's laws and related principles can be applied in solving all the problems. However, microelectronics is not as clean as these courses. There are hundreds of equations for different circuits, and it is impossible to remember which equation should be applied to which circuit. One of the common pitfalls in learning this course is over-focusing at the equation level and ignoring the ideas (Tao) behind it. Unfortunately, these ideas are not summarized and emphasized in most microelectronics textbooks, though they cover various electronic circuits comprehensively. Therefore, most undergraduate students feel at a loss when they start to learn this topic. This book tries to illustrate the major ideas and the basic analysis techniques, so that students can derive the right equations easily when facing an electronic circuit.

Research and Energy Efficiency: Selected Success Stories

DOE R&D Accomplishments Database

Garland, P. W.; Garland, R. W.

1997-06-26

Energy use and energy technology play critical roles in the U.S. economy and modern society. The Department of Energy (DOE) conducts civilian energy research and development (R&D) programs for the purpose of identifying promising technologies that promote energy security, energy efficiency, and renewable energy use. DOE-sponsored research ranges from basic investigation of phenomena all the way through development of applied technology in partnership with industry. DOE`s research programs are conducted in support of national strategic energy objectives, however austere financial times have dictated that R&D programs be measured in terms of cost vs. benefit. In some cases it is difficult to measure the return on investment for the basic "curiosity-driven" research, however many applied technology development programs have resulted in measurable commercial successes. The DOE has published summaries of their most successful applied technology energy R&D programs. In this paper, we will discuss five examples from the Building Technologies area of the DOE Energy Efficiency program. Each story will describe the technology, discuss the level of federal funding, and discuss the returns in terms of energy savings, cost savings, or national economic impacts.

Glycan Arrays: From Basic Biochemical Research to Bioanalytical and Biomedical Applications

NASA Astrophysics Data System (ADS)

Geissner, Andreas; Seeberger, Peter H.

2016-06-01

A major branch of glycobiology and glycan-focused biomedicine studies the interaction between carbohydrates and other biopolymers, most importantly, glycan-binding proteins. Today, this research into glycan-biopolymer interaction is unthinkable without glycan arrays, tools that enable high-throughput analysis of carbohydrate interaction partners. Glycan arrays offer many applications in basic biochemical research, for example, defining the specificity of glycosyltransferases and lectins such as immune receptors. Biomedical applications include the characterization and surveillance of influenza strains, identification of biomarkers for cancer and infection, and profiling of immune responses to vaccines. Here, we review major applications of glycan arrays both in basic and applied research. Given the dynamic nature of this rapidly developing field, we focus on recent findings.

Statistics for nuclear engineers and scientists. Part 1. Basic statistical inference

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

Beggs, W.J.

1981-02-01

This report is intended for the use of engineers and scientists working in the nuclear industry, especially at the Bettis Atomic Power Laboratory. It serves as the basis for several Bettis in-house statistics courses. The objectives of the report are to introduce the reader to the language and concepts of statistics and to provide a basic set of techniques to apply to problems of the collection and analysis of data. Part 1 covers subjects of basic inference. The subjects include: descriptive statistics; probability; simple inference for normally distributed populations, and for non-normal populations as well; comparison of two populations; themore » analysis of variance; quality control procedures; and linear regression analysis.« less

Basic charasteristics of information system of health insurance in FB&H.

PubMed

Dzubur, Amela; Besić, Asim; Omanić, Ajnija; Dzubur, Alen; Niksić, Dragana

2004-10-01

Due to the territorial and administrative division in the war period, information system of health protection after the war was divided in two systems, what matched organisation of health insurance in that period. Those information systems were incompatible, developed on different, both, hardware and software. Therefore, Ministry of Health, within the project "Basic hospital services", financed through the World Bank loan, applied new, common information system in health insurance. Goal of this paper is to present basic features of information system of health insurance in FB&H, as well as the way of its functioning in respect to other institutions included in the system, respective data bases, sites of entering and updating data, while using data available with Federal Bureau of Health Insurance.

NREL Supports Native American Tribes in Clean Energy Transformational

Science.gov Websites

information to design, fund, and implement renewable energy systems," Ganion said. "And by actively receive a basic evaluative study from NREL on the emerging biomass gasification technology, as applied to

Apply for a Research Grant

Cancer.gov

The NCI Grants Process provides an overview of the end-to-end lifecycle of grant funding. Learn about the types of funding available and the basics for application, review, award, and on-going administration within the NCI.

Applying for and using CMAQ funds

DOT National Transportation Integrated Search

1997-01-01

This guide provides the basic concepts to aid in an alternative fuel vehicle market development program developing an application for Congestion Mitigation and Air Quality (CMAQ) Improvement Program funding. The U.S. Department of Energy's Clean Citi...

48 CFR 45.107 - Contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Alternate II when a contract for the conduct of basic or applied research at nonprofit institutions of... research (see 35.014) is contemplated. (b) The contracting officer shall also insert the clause at 52.245-2...

40 CFR 63.7852 - What definitions apply to this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... hot metal, usually with dry air or nitrogen, to remove sulfur. Deviation means any instance in which... capture and collection of secondary emissions from a basic oxygen process furnace. Sinter cooler means the...

40 CFR 63.7852 - What definitions apply to this subpart?

Code of Federal Regulations, 2010 CFR

2010-07-01

... hot metal, usually with dry air or nitrogen, to remove sulfur. Deviation means any instance in which... capture and collection of secondary emissions from a basic oxygen process furnace. Sinter cooler means the...

40 CFR 63.7852 - What definitions apply to this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... hot metal, usually with dry air or nitrogen, to remove sulfur. Deviation means any instance in which... capture and collection of secondary emissions from a basic oxygen process furnace. Sinter cooler means the...

40 CFR 63.7852 - What definitions apply to this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... hot metal, usually with dry air or nitrogen, to remove sulfur. Deviation means any instance in which... capture and collection of secondary emissions from a basic oxygen process furnace. Sinter cooler means the...

40 CFR 63.7852 - What definitions apply to this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... hot metal, usually with dry air or nitrogen, to remove sulfur. Deviation means any instance in which... capture and collection of secondary emissions from a basic oxygen process furnace. Sinter cooler means the...

Proceedings of the First ERDA Semiannual Solar Photovoltaic Conversion Program Conference

NASA Technical Reports Server (NTRS)

1975-01-01

Organization, basic research and applied technology for the Solar Photovoltaic Conversion Program are outlined. The program aims to provide a technology base for low cost thin film solar cells and solar arrays.

42 CFR 65a.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH... this part. (b) Awardee institutions may carry out portions of the research or training components of an...

42 CFR 65a.3 - Who is eligible to apply for a grant?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH... this part. (b) Awardee institutions may carry out portions of the research or training components of an...

Genetics

USDA-ARS?s Scientific Manuscript database

The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

Really a Matter of Data: A Reply to Solomon.

ERIC Educational Resources Information Center

Sroufe, L. Alan

1980-01-01

Replies to Solomon's paper that basic criticisms made earlier of Shaffran and Decaries' study still apply. Views the study as essentially a confirmation of the null hypothesis based on weak measures. (Author/RH)

Christine English | NREL

Science.gov Websites

Hydrogenases: New Frontiers in Basic and Applied Studies for Biological and Synthetic H2 Production. Dalton Histone H3 in S-Phase. Journal of Biological Chemistry, 12, 1334-1340. English, C.M., Adkins, M.W

Can Clinical Scenario Videos Improve Dental Students' Perceptions of the Basic Sciences and Ability to Apply Content Knowledge?

PubMed

Miller, Cynthia Jayne; Metz, Michael James

2015-12-01

Dental students often have difficulty understanding the importance of basic science classes, such as physiology, for their future careers. To help alleviate this problem, the aim of this study was to create and evaluate a series of video modules using simulated patients and custom-designed animations that showcase medical emergencies in the dental practice. First-year students in a dental physiology course formatively assessed their knowledge using embedded questions in each of the three videos; 108 to 114 of the total 120 first-year students answered the questions, for a 90-95% response rate. These responses indicated that while the students could initially recognize the cause of the medical emergency, they had difficulty in applying their knowledge of physiology to the scenario. In two of the three videos, students drastically improved their ability to answer high-level clinical questions at the conclusion of the video. Additionally, when compared to the previous year of the course, there was a significant improvement in unit exam scores on clinically related questions (6.2% increase). Surveys were administered to the first-year students who participated in the video modules and fourth-year students who had completed the course prior to implementation of any clinical material. The response rate for the first-year students was 96% (115/120) and for the fourth-year students was 57% (68/120). The first-year students indicated a more positive perception of the physiology course and its importance for success on board examinations and their dental career than the fourth-year students. The students perceived that the most positive aspects of the modules were the clear applications of physiology to real-life dental situations, the interactive nature of the videos, and the improved student comprehension of course concepts. These results suggest that online modules may be used successfully to improve students' perceptions of the basic sciences and enhance their ability to apply basic science content to clinically important scenarios.

Basic energy sciences: Summary of accomplishments

NASA Astrophysics Data System (ADS)

1990-05-01

For more than four decades, the Department of Energy, including its predecessor agencies, has supported a program of basic research in nuclear- and energy related sciences, known as Basic Energy Sciences. The purpose of the program is to explore fundamental phenomena, create scientific knowledge, and provide unique user facilities necessary for conducting basic research. Its technical interests span the range of scientific disciplines: physical and biological sciences, geological sciences, engineering, mathematics, and computer sciences. Its products and facilities are essential to technology development in many of the more applied areas of the Department's energy, science, and national defense missions. The accomplishments of Basic Energy Sciences research are numerous and significant. Not only have they contributed to Departmental missions, but have aided significantly the development of technologies which now serve modern society daily in business, industry, science, and medicine. In a series of stories, this report highlights 22 accomplishments, selected because of their particularly noteworthy contributions to modern society. A full accounting of all the accomplishments would be voluminous. Detailed documentation of the research results can be found in many thousands of articles published in peer-reviewed technical literature.

Development of conditioning programs for dressage horses based on time-motion analysis of competitions.

PubMed

Clayton, H M

1993-05-01

The time-motion characteristics of Canadian basic- and medium-level dressage competitions are described, and the results are applied in formulating sport-specific conditioning programs. One competition was analyzed at the six levels from basic 1 to medium 3. Each test was divided into a series of sequences based on the type and speed of activity. The durations of the sequences were measured from videotapes. The basic-level tests had fewer sequences, and they were shorter in distance and duration than the medium tests (P < 0.10), but the average speed did not differ between the two levels. It is recommended that horses competing at the basic levels be conditioned using 5-min exercise periods, with short (10-s) bursts of lengthened trot and canter included at basic 2 and above. In preparation for medium-level competitions, the duration of the work periods increases to 7 min, 10- to 12-s bursts of medium or extended trot and canter are included, and transitions are performed frequently to simulate the energy expenditure in overcoming inertia.

Basic Energy Sciences: Summary of Accomplishments

DOE R&D Accomplishments Database

1990-05-01

For more than four decades, the Department of Energy, including its predecessor agencies, has supported a program of basic research in nuclear- and energy-related sciences, known as Basic Energy Sciences. The purpose of the program is to explore fundamental phenomena, create scientific knowledge, and provide unique user'' facilities necessary for conducting basic research. Its technical interests span the range of scientific disciplines: physical and biological sciences, geological sciences, engineering, mathematics, and computer sciences. Its products and facilities are essential to technology development in many of the more applied areas of the Department's energy, science, and national defense missions. The accomplishments of Basic Energy Sciences research are numerous and significant. Not only have they contributed to Departmental missions, but have aided significantly the development of technologies which now serve modern society daily in business, industry, science, and medicine. In a series of stories, this report highlights 22 accomplishments, selected because of their particularly noteworthy contributions to modern society. A full accounting of all the accomplishments would be voluminous. Detailed documentation of the research results can be found in many thousands of articles published in peer-reviewed technical literature.

Suppression of innate inflammation and immunity by interleukin-37.

PubMed

Dinarello, Charles A; Nold-Petry, Claudia; Nold, Marcel; Fujita, Mayumi; Li, Suzhao; Kim, Soohyun; Bufler, Philip

2016-05-01

IL-37 is unique in the IL-1 family in that unlike other members of the family, IL-37 broadly suppresses innate immunity. IL-37 can be elevated in humans with inflammatory and autoimmune diseases where it likely functions to limit inflammation. Transgenic mice expressing human IL-37 (IL37-tg) exhibit less severe inflammation in models of endotoxin shock, colitis, myocardial infarction, lung, and spinal cord injury. IL37-tg mice have reduced antigen-specific responses and dendritic cells (DCs) from these mice exhibit characteristics of tolerogenic DCs. Compared to aging wild-type (WT) mice, aging IL37-tg mice are protected against B-cell leukemogenesis and heart failure. Treatment of WT mice with recombinant human IL-37 has been shown to be protective in several models of inflammation and injury. IL-37 binds to the IL-18 receptor but then recruits the orphan IL-1R8 (formerly TIR8 or SIGIRR) in order to function as an inhibitor. Here, we review the discovery of IL-37, its production, release, and mechanisms by which IL-37 reduces inflammation and suppresses immune responses. The data reviewed here suggest a therapeutic potential for IL-37. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long Non-Coding RNAs in Haematological Malignancies

PubMed Central

Garitano-Trojaola, Andoni; Agirre, Xabier; Prósper, Felipe; Fortes, Puri

2013-01-01

Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. LncRNAs are as diverse as mRNAs and they normally share the same biosynthetic machinery based on RNA polymerase II, splicing and polyadenylation. However, lncRNAs have low coding potential. Compared to mRNAs, lncRNAs are preferentially nuclear, more tissue specific and expressed at lower levels. Most of the lncRNAs described to date modulate the expression of specific genes by guiding chromatin remodelling factors; inducing chromosomal loopings; affecting transcription, splicing, translation or mRNA stability; or serving as scaffolds for the organization of cellular structures. They can function in cis, cotranscriptionally, or in trans, acting as decoys, scaffolds or guides. These functions seem essential to allow cell differentiation and growth. In fact, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in several cancers including haematological malignancies. In this review, we summarize what is known about lncRNAs, the mechanisms for their regulation in cancer and their role in leukemogenesis, lymphomagenesis and hematopoiesis. Furthermore, we discuss the potential of lncRNAs in diagnosis, prognosis and therapy in cancer, with special attention to haematological malignancies. PMID:23887658

Recent advances in acute lymphoblastic leukemia in children and adolescents: an expert panel discussion.

PubMed

Asselin, Barbara L; Gaynon, Paul; Whitlock, James A

2013-12-01

Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia, representing 75% to 80% of cases of acute leukemia among children. Dramatic improvements in the cure rates and survival outcomes for children with ALL have been seen over the past several decades; currently the 5-year survival rate for childhood ALL is more than 80%. These improvements have come about because of advances in the understanding of the molecular genetics and pathogenesis of the disease, incorporation of risk-adapted therapy, and the advent of new targeted agents. Scientific advances have provided new insights into leukemogenesis, drug resistance, and host pharmacogenomics, identified novel subtypes of leukemia, and suggested potential targets for therapy. At the same time novel monoclonal antibodies, small molecule inhibitors, chemotherapeutics, and cell-based treatment strategies have been developed and investigated. In this article, experts will discuss some of the current challenges and future directions in the treatment of pediatric ALL. The authors will offer expert guidance to practicing oncologists on how to best incorporate newer treatment approaches into the care of children and adolescents with ALL. The most important ongoing clinical trials in the area will also be reviewed.

Cytoplasmic FANCA-FANCC Complex Interacts and Stabilizes the Cytoplasm-dislocalized Leukemic Nucleophosmin Protein (NPMc)*

PubMed Central

Du, Wei; Li, Jie; Sipple, Jared; Chen, Jianjun; Pang, Qishen

2010-01-01

Eight of the Fanconi anemia (FA) proteins form a core complex that activates the FA pathway. Some core complex components also form subcomplexes for yet-to-be-elucidated functions. Here, we have analyzed the interaction between a cytoplasmic FA subcomplex and the leukemic nucleophosmin (NPMc). Exogenous NPMc was degraded rapidly in FA acute myeloid leukemia bone marrow cells. Knockdown of FANCA or FANCC in leukemic OCI/AML3 cells induced rapid degradation of endogenous NPMc. NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. Moreover, cytoplasmic FANCA and FANCC formed a cytoplasmic complex and interacted with NPMc. Using a patient-derived FANCC mutant and a nuclearized FANCC, we demonstrated that the cytoplasmic FANCA-FANCC complex was essential for NPMc stability. Finally, depletion of FANCA and FANCC in NPMc-positive leukemic cells significantly increased inflammation and chemoresistance through NF-κB activation. Our findings not only reveal the molecular mechanism involving cytoplasmic retention of NPMc but also suggest cytoplasmic function of FANCA and FANCC in NPMc-related leukemogenesis. PMID:20864535

Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility

PubMed Central

Meyer, Stefan; Ravandi-Kashani, Farhad; Borthakur, Gautam; Coombes, Kevin R.; Zhang, Nianxiang; Kornblau, Steven

2016-01-01

Acute myeloid leukemia (AML) is a heterogenous disease with differential oncogene association, outcome and treatment regimens. Treatment strategies for AML have improved outcome but despite increased molecular biological information AML is still associated with poor prognosis. Proteomic analysis on the effects of a range of leukemogenic oncogenes showed that the protein transglutaminase 2 (TG2) is expressed at greater levels as a consequence of oncogenic transformation. Further analysis of this observation was performed with 511 AML samples using reverse phase proteomic arrays, demonstrating that TG2 expression was higher at relapse than diagnosis in many cases. In addition elevated TG2 expression correlated with increased expression of numerous adhesion proteins and many apoptosis regulating proteins, two processes related to leukemogenesis. TG2 has previously been linked to drug resistance in cancer and given the negative correlation between TG2 levels and peripheral blasts observed increased TG2 levels may lead to the protection of the leukemic stem cell due to increased adhesion/reduced motility. TG2 may therefore form part of a network of proteins that define poor outcome in AML patients and potentially offer a target to sensitize AML stem cells to drug treatment. PMID:23576428

Novel approaches to diagnosis and treatment of Juvenile Myelomonocytic Leukemia.

PubMed

Locatelli, Franco; Algeri, Mattia; Merli, Pietro; Strocchio, Luisa

2018-02-01

Juvenile myelomonocytic leukemia (JMML) is a clonal hematopoietic disorder of infancy/early childhood, resulting from oncogenic mutations in genes involved in the Ras pathway. As JMML often exhibits an aggressive course, the timing of diagnosis and treatment is critical to outcome. Areas covered: This review summarizes current approaches to diagnosis and treatment of JMML, highlighting most recent insights into genetic and epigenetic mechanisms underlying the disease, and providing an overview of novel potential therapeutic strategies. Expert commentary: At present, allogeneic HSCT remains the only potentially effective therapy, being able to cure more than 50% of patients, relapse representing the main cause of treatment failure. Prompt HSCT is recommended for all children with NF1, somatic PTPN11 and KRAS mutations, and for most children with somatic NRAS mutations. Conversely, a 'watch and wait' strategy should be adopted in children with germline CBL mutations, specific somatic NRAS mutation, and in Noonan syndrome patients, since spontaneous resolution has been reported to occur. Novel drugs targeting relevant nodes of JMML leukemogenesis have been explored in pre-HSCT window or at relapse. The use of 5-azacytidine, a DNA-hypomethylating agent reported to induce hematologic and molecular remission in some JMML children, is currently being investigated in clinical trials.

EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

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

Nagareda, C.S.; Kaplan, H.S.

1959-04-01

Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations.

PubMed

Ebens, Christen L; MacMillan, Margaret L; Wagner, John E

2017-01-01

Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.

Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia.

PubMed

Lanemo Myhrinder, Anna; Hellqvist, Eva; Bergh, Ann-Charlotte; Jansson, Mattias; Nilsson, Kenneth; Hultman, Per; Jonasson, Jon; Buhl, Anne Mette; Bredo Pedersen, Lone; Jurlander, Jesper; Klein, Eva; Weit, Nicole; Herling, Marco; Rosenquist, Richard; Rosén, Anders

2013-08-01

Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.

Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes.

PubMed

Zaragoza, Katrin; Bégay, Valérie; Schuetz, Anja; Heinemann, Udo; Leutz, Achim

2010-05-01

The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/EBPalpha transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity toward DNA and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.

Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis.

PubMed

Selvakumaran, M; Liebermann, D; Hoffman-Liebermann, B

1993-05-01

Conditional mutants of the myeloblastic leukemic M1 cell line, expressing the chimeric mycer transgene, have been established. It is shown that M1 mycer cells, like M1, undergo terminal differentiation coupled to growth arrest and programmed cell death (apoptosis) after treatment with the physiologic differentiation inducer interleukin-6. However, when beta-estradiol is included in the culture medium, M1 mycer cells respond to differentiation inducers like M1 myc cell lines, where the differentiation program is blocked at an intermediate stage. By manipulating the function of the mycer transgene product, it is shown that there is a 10-hour window during myeloid differentiation, from 30 to 40 hours after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, where activation of c-myc has no apparent effect on mature macrophages. M1 mycer cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal myelopoiesis and in leukemogenesis, also providing a strategy to clone c-myc target genes.

Seroprevalence of human herpes simplex, hepatitis B and epstein-barr viruses in children with acute lymphoblastic leukemia in southern iran.

PubMed

Mahjour, Seyed Babak; Ghaffarpasand, Fariborz; Fattahi, Mohammad Javad; Ghaderi, Abbas; Fotouhi Ghiam, Alireza; Karimi, Mehran

2010-12-01

To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age-sex matched healthy participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA) were measured by enzyme-linked immunosorbent assay (ELISA). There were 54 (60%) male and 36 (40%) female in both study groups with mean age of 8.47 ± 3.61 and 8.61 ± 2.84 years in case and control group respectively (P = 0.812). The prevalence of antibodies against HBsAg (P = 0.002), HSV1 (P < 0.0001), VCA (P = 0.021) and EA (P < 0.0001) antigens of EBV were significantly higher in ALL patients. With the results of this study, we could not exclude a connection between these viral infections and later leukemogenesis in childhood ALL, although nor latent infection nor congenital infection cannot be excluded by this method.

Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner

PubMed Central

2013-01-01

The current study evaluated the differential expression detected in the proteomic profiles of low risk- and high risk- ALL pediatric patients to characterize candidate biomarkers related to diagnosis, prognosis and patient targeted therapy. Bone marrow and peripheral blood plasma and cell lysates samples were obtained from pediatric patients with low- (LR) and high-risk (HR) ALL at diagnosis. As controls, non-leukemic pediatric patients were studied. Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization. Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The differential expression of certain proteins was confirmed by Western blot analysis. The obtained data revealed that CLUS, CERU, APOE, APOA4, APOA1, GELS, S10A9, AMBP, ACTB, CATA and AFAM proteins play a significant role in leukemia prognosis, potentially serving as distinctive biomarkers for leukemia aggressiveness, or as suppressor proteins in HR-ALL cases. In addition, vitronectin and plasminogen probably contributed to leukemogenesis, whilst bicaudal D-related protein 1 could afford a significant biomarker for pediatric ALL therapeutics. PMID:23849470

Targeting the TAM Receptors in Leukemia.

PubMed

Huey, Madeline G; Minson, Katherine A; Earp, H Shelton; DeRyckere, Deborah; Graham, Douglas K

2016-11-08

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

Ski can negatively regulates macrophage differentiation through its interaction with PU.1

PubMed Central

Ueki, N; Zhang, L; Haymann, MJ

2010-01-01

In the hematopoietic cell system, the oncoprotein Ski dramatically affects growth and differentiation programs, in some cases leading to malignant leukemia. However, little is known about the interaction partners or signaling pathways involved in the Ski-mediated block of differentiation in hematopoietic cells. Here we show that Ski interacts with PU.1, a lineage-specific transcription factor essential for terminal myeloid differentiation, and thereby represses PU.1-dependent transcriptional activation. Consistent with this, Ski inhibits the biological function of PU.1 to promote myeloid cells to differentiate into macrophage colony-stimulating factor receptor (M-CSFR)-positive macrophages. Using a Ski mutant deficient in PU.1 binding, we demonstrate that Ski–PU.1 interaction is critical for Ski's ability to repress PU.1-dependent transcription and block macrophage differentiation. Furthermore, we provide evidence that Ski-mediated repression of PU.1 is due to Ski's ability to recruit histone deacetylase 3 to PU.1 bound to DNA. Since inactivation of PU.1 is closely related to the development of myeloid leukemia and Ski strongly inhibits PU.1 function, we propose that aberrant Ski expression in certain types of myeloid cell lineages might contribute to leukemogenesis. PMID:17621263

Detecting Autophagy and Autophagy Flux in Chronic Myeloid Leukemia Cells Using a Cyto-ID Fluorescence Spectrophotometric Assay.

PubMed

Guo, Sujuan; Pridham, Kevin J; Sheng, Zhi

2016-01-01

Autophagy is a catabolic process whereby cellular components are degraded to fuel cells for longer survival during stress. Hence, autophagy plays a vital role in determining cell fate and is central for homeostasis and pathogenesis of many human diseases including chronic myeloid leukemia (CML). It has been well established that autophagy is important for the leukemogenesis as well as drug resistance in CML. Thus, autophagy is an intriguing therapeutic target. However, current approaches that detect autophagy lack reliability and often fail to provide quantitative measurements. To overcome this hurdle and facilitate the development of autophagy-related therapies, we have recently developed an autophagy assay termed as the Cyto-ID fluorescence spectrophotometric assay. This method uses a cationic fluorescence dye, Cyto-ID, which specifically labels autophagic compartments and is detected by a spectrophotometer to permit a large-scale and quantitative analysis. As such, it allows rapid, reliable, and quantitative detection of autophagy and estimation of autophagy flux. In this chapter, we further provide technical details of this method and step-by-step protocols for measuring autophagy or autophagy flux in CML cell lines as well as primary hematopoietic cells.

Deletion of TAK1 in the Myeloid Lineage Results in the Spontaneous Development of Myelomonocytic Leukemia in Mice

PubMed Central

Lamothe, Betty; Lai, YunJu; Hur, Lana; Orozco, Natalia Martin; Wang, Jing; Campos, Alejandro D.; Xie, Min; Schneider, Michael D.; Lockworth, Cynthia R.; Jakacky, Jared; Tran, Diep; Ho, Michael; Dawud, Sity; Dong, Chen; Lin, Hui-Kuan; Hu, Peter; Estrov, Zeev; Bueso-Ramos, Carlos E.; Darnay, Bryant G.

2012-01-01

Previous studies of the conditional ablation of TGF-β activated kinase 1 (TAK1) in mice indicate that TAK1 has an obligatory role in the survival and/or development of hematopoietic stem cells, B cells, T cells, hepatocytes, intestinal epithelial cells, keratinocytes, and various tissues, primarily because of these cells’ increased apoptotic sensitivity, and have implicated TAK1 as a critical regulator of the NF-κB and stress kinase pathways and thus a key intermediary in cellular survival. Contrary to this understanding of TAK1’s role, we report a mouse model in which TAK1 deletion in the myeloid compartment that evoked a clonal myelomonocytic cell expansion, splenomegaly, multi-organ infiltration, genomic instability, and aggressive, fatal myelomonocytic leukemia. Unlike in previous reports, simultaneous deletion of TNF receptor 1 (TNFR1) failed to rescue this severe phenotype. We found that the features of the disease in our mouse model resemble those of human chronic myelomonocytic leukemia (CMML) in its transformation to acute myeloid leukemia (AML). Consequently, we found TAK1 deletion in 13 of 30 AML patients (43%), thus providing direct genetic evidence of TAK1’s role in leukemogenesis. PMID:23251462

Discrete square root smoothing.

NASA Technical Reports Server (NTRS)

Kaminski, P. G.; Bryson, A. E., Jr.

1972-01-01

The basic techniques applied in the square root least squares and square root filtering solutions are applied to the smoothing problem. Both conventional and square root solutions are obtained by computing the filtered solutions, then modifying the results to include the effect of all measurements. A comparison of computation requirements indicates that the square root information smoother (SRIS) is more efficient than conventional solutions in a large class of fixed interval smoothing problems.

Analysis of Learning Curve Fitting Techniques.

DTIC Science & Technology

1987-09-01

1986. 15. Neter, John and others. Applied Linear Regression Models. Homewood IL: Irwin, 19-33. 16. SAS User’s Guide: Basics, Version 5 Edition. SAS... Linear Regression Techniques (15:23-52). Random errors are assumed to be normally distributed when using -# ordinary least-squares, according to Johnston...lot estimated by the improvement curve formula. For a more detailed explanation of the ordinary least-squares technique, see Neter, et. al., Applied

Student Improvement by Applying the Numbered Heads Together (NHT) Approach to Basic Subjects of Vocational Competence in a Vocational High School in Indonesia

ERIC Educational Resources Information Center

Wora, Veronika Marta; Hadisaputro, Ranto; Rohman, Ngatou; Bugis, Husin; Pambudi, Suharno Nugroho Agung

2017-01-01

This research aims to improve the learning activity and achievement of a 10th grade class made up of 30 students in a vocational high school located in the city of Surakarta, Indonesia, by applying the Numbered Heads Together (NHT) approach. The experiment was divided into two stages of four activities each: planning, implementation, observation,…