Downregulation of deoxycytidine kinase in cytarabine-resistant mantle cell lymphoma cells confers cross-resistance to nucleoside analogs gemcitabine, fludarabine and cladribine, but not to other classes of anti-lymphoma agents

PubMed Central

2014-01-01

Background Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma associated with poor prognosis. Implementation of high-dose cytarabine (araC) into induction therapy became standard-of-care for all newly diagnosed younger MCL patients. However, many patients relapse even after araC-based regimen. Molecular mechanisms responsible for araC resistance in MCL are unknown and optimal treatment strategy for relapsed/refractory MCL patients remains elusive. Methods Five araC-resistant (R) clones were derived by long-term culture of five MCL cell lines (CTRL) with increasing doses of araC up to 50 microM. Illumina BeadChip and 2-DE proteomic analysis were used to identify gene and protein expression changes associated with araC resistance in MCL. In vitro cytotoxicity assays and experimental therapy of MCL xenografts in immunodeficient mice were used to analyze their relative responsiveness to a set of clinically used anti-MCL drugs. Primary MCL samples were obtained from patients at diagnosis and after failure of araC-based therapies. Results Marked downregulation of deoxycytidine-kinase (DCK) mRNA and protein expression was identified as the single most important molecular event associated with araC-resistance in all tested MCL cell lines and in 50% primary MCL samples. All R clones were highly (20-1000x) cross-resistant to all tested nucleoside analogs including gemcitabine, fludarabine and cladribine. In vitro sensitivity of R clones to other classes of clinically used anti-MCL agents including genotoxic drugs (cisplatin, doxorubicin, bendamustine) and targeted agents (bortezomib, temsirolimus, rituximab) remained unaffected, or was even increased (ibrutinib). Experimental therapy of immunodeficient mice confirmed the anticipated loss of anti-tumor activity (as determined by overall survival) of the nucleoside analogs gemcitabine and fludarabine in mice transplanted with R clone compared to mice transplanted with CTRL cells, while the anti-tumor activity of cisplatin, temsirolimus, bortezomib, bendamustine, cyclophosphamide and rituximab remained comparable between the two cohorts. Conclusions Acquired resistance of MCL cells to araC is associated with downregulation of DCK, enzyme of the nucleotide salvage pathway responsible for the first phosphorylation (=activation) of most nucleoside analogs used in anti-cancer therapy. The data suggest that nucleoside analogs should not be used in the therapy of MCL patients, who relapse after failure of araC-based therapies. PMID:24972933

Cytosine arabinoside influx and nucleoside transport sites in acute leukemia.

PubMed

Wiley, J S; Jones, S P; Sawyer, W H; Paterson, A R

1982-02-01

Although cytosine arabinoside (araC) can induce a remission in a majority of patients presenting with acute myeloblastic leukemia (AML), a minority fail to respond and moreover the drug has less effect in acute lymphoblastic leukemia (ALL). The carrier-mediated influx of araC into purified blasts from patients with AML, ALL, and acute undifferentiated leukemia (AUL) has been compared to that of normal lymphocytes and polymorphs. Blasts showed a larger mediated influx of araC than mature cells, since mean influxes for myeloblasts and lymphoblasts were 6- and 2.3-fold greater than polymorphs and lymphocytes, respectively. Also, the mean influx for myeloblasts was fourfold greater than the mean for lymphoblasts. The number of nucleoside transport sites was estimated for each cell type by measuring the equilibrium binding of [(3)H]nitrobenzylthioinosine (NBMPR), which inhibits nucleoside fluxes by binding with high affinity to specific sites on the transport mechanism. The mean binding site numbers for myeloblasts and lymphoblasts were 5- and 2.8-fold greater, respectively, than for the mature cells of the same maturation series. The mean number of NBMPR binding sites for myeloblasts was fourfold greater than for lymphoblasts. Patients with AUL were heterogeneous since blasts from some gave values within the myeloblastic range and others within the lymphoblastic range. The araC influx correlated closely with the number of NBMPR binding sites measured in the same cells on the same day. Transport parameters were measured on blasts from 15 patients with AML or AUL who were then treated with standard induction therapy containing araC. Eight patients entered complete remission, while seven failed therapy, among whom were the three patients with the lowest araC influx (<0.4 pmol/10(7) cells per min) and NBMPR binding (<3,000 sites/cell) for the treated group. In summary, myeloblasts have both higher araC transport rates and more nucleoside transport sites than lymphoblasts and this factor may contribute to the greater sensitivity of AML to this drug. AraC transport varied >10-fold between leukemic blasts and normal leukocytes, but transport capacity related directly to the number of nucleoside transport sites on the cell. Finally, low araC transport rates or few NBMPR binding sites on blasts were observed in a subset of patients with acute leukemia who failed to achieve remission with drug combinations containing araC.

Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid leukemia (AML) and the effect of pharmacological inhibition of Nrf2.

PubMed

Karathedath, Sreeja; Rajamani, Bharathi M; Musheer Aalam, Syed Mohammed; Abraham, Ajay; Varatharajan, Savitha; Krishnamurthy, Partha; Mathews, Vikram; Velayudhan, Shaji Ramachandran; Balasubramanian, Poonkuzhali

2017-01-01

Cytarabine (Ara-C) and Daunorubicin (Dnr) forms the backbone of acute myeloid leukemia (AML) therapy. Drug resistance and toxic side effects pose a major threat to treatment success and hence alternate less toxic therapies are warranted. NF-E2 related factor-2 (Nrf2), a master regulator of antioxidant response is implicated in chemoresistance in solid tumors. However, little is known about the role of Nrf2 in AML chemoresistance and the effect of pharmacological inhibitor brusatol in modulating this resistance. Primary AML samples with high ex-vivo IC50 to Ara-C, ATO, Dnr had significantly high NRF2 RNA expression. Gene-specific knockdown of NRF2 improved sensitivity to these drugs in resistant AML cell lines by decreasing the expression of downstream antioxidant targets of Nrf2 by compromising the cell's ability to scavenge the ROS. Treatment with brusatol, a pharmacological inhibitor of Nrf2, improved sensitivity to Ara-C, ATO, and Dnr and reduced colony formation capacity. AML cell lines stably overexpressing NRF2 showed increased resistance to ATO, Dnr and Ara-C and increased expression of downstream targets. This study demonstrates that Nrf2 could be an ideal druggable target in AML, more so to the drugs that function through ROS, suggesting the possibility of using Nrf2 inhibitors in combination with chemotherapeutic agents to modulate drug resistance in AML.

Protective effect of β-D-glucan and glutamine on the genomic instability induced by Cytarabine/Ara-C in BALB/c mice.

PubMed

de Souza Silva, Priscilla Mirian; de Sousa, Raimundo Vicente; Simão, Anderson Assaid; Cesar, Pedro Henrique Souza; Trento, Marcus Vinicius Cardoso; Marcussi, Silvana

2018-05-28

Prophylactic antibiotics and growth promoters have been substituted, mainly for livestock, by immunomodulators and intestinal health promoters - such as β-D-glucans and glutamine. The aim of this study was to verify the beneficial effects of β-D-glucans and glutamine against Cytarabine/Ara-C, evaluating the DNA damage in leukocytes, the leukogram, and the mitotic index of intestinal crypts cells. Balb/C mice received treatment with β-D-glucan (80 mg/Kg), glutamine (150 mg/Kg), or both, for 21 days. On the last two days of this period, Ara-C was administered (1.8 mg/animal) by intraperitoneal injection every 12 h. The animals submitted to the treatment with Ara-C presented the highest genotoxic index, a significant leukopenia, and a decrease in the mitotic index of the intestinal crypts cells. Treatment with β-D-glucan protected the leukocytes against DNA fragmentation induced by Ara-C. Glutamine alone promoted maintenance of the mitotic index and, in association with β-Dglucan, reduced leukopenia. Thus, the use of β-D-glucan and glutamine proved to be beneficial to intestinal tropism. This can happen once the damage to the genetic material, prevented by the treatments with β-D-glucan and glutamine, can result in genotoxicity. Not only this, but it might be capable of turning into a mutagenesis, with consequential physiopathological alterations. Copyright © 2018. Published by Elsevier B.V.

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

PubMed

Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

1990-02-28

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

Histone deacetylase inhibitors reduce differentiating osteoblast-mediated protection of acute myeloid leukemia cells from cytarabine

PubMed Central

Sterner, Rosalie M.; Kremer, Kimberly N.; Al-Kali, Aref; Patnaik, Mrinal M.; Gangat, Naseema; Litzow, Mark R.; Kaufmann, Scott H.; Westendorf, Jennifer J.; van Wijnen, Andre J.; Hedin, Karen E.

2017-01-01

The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts. Moreover, pretreating differentiating osteoblasts with the histone deacetylase inhibitors (HDACi) vorinostat and panobinostat abrogated the ability of the differentiating osteoblasts to protect AML cells. Together, our results indicate that differentiating osteoblasts have the potential to promote residual AML in the bone marrow following standard chemotherapy and act via a mechanism requiring HDACi-sensitive gene expression. Using HDACi to target the leukemic microenvironment in combination with Ara-C could potentially improve treatment of AML. Moreover, other strategies for manipulating bone marrow osteoblasts may also help eradicate AML cells and reduce relapse. PMID:29212250

Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis.

PubMed

Chen, Wei; Zhang, Shan; Jiang, Peixia; Yao, Jun; He, Yongzhi; Chen, Lincai; Gui, Xiwu; Dong, Zhiyang; Tang, Shuang-Yan

2015-07-01

Advanced high-throughput screening methods for small molecules may have important applications in the metabolic engineering of the biosynthetic pathways of these molecules. Ectoine is an excellent osmoprotectant that has been widely used in cosmetics. In this study, the Escherichia coli regulatory protein AraC was engineered to recognize ectoine as its non-natural effector and to activate transcription upon ectoine binding. As an endogenous reporter of ectoine, the mutated AraC protein was successfully incorporated into high-throughput screening of ectoine hyper-producing strains. The ectoine biosynthetic cluster from Halomonas elongata was cloned into E. coli. By engineering the rate-limiting enzyme L-2,4-diaminobutyric acid (DABA) aminotransferase (EctB), ectoine production and the specific activity of the EctB mutant were increased. Thus, these results demonstrated the effectiveness of engineering regulatory proteins into sensitive and rapid screening tools for small molecules and highlighted the importance and efficacy of directed evolution strategies applied to the engineering of genetic components for yield improvement in the biosynthesis of small molecules. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Autophagy is an important event for low-dose cytarabine treatment in acute myeloid leukemia cells.

PubMed

Chen, Liyun; Guo, Pei; Zhang, Yunxiang; Li, Xiaoyang; Jia, Peimin; Tong, Jianhua; Li, Junmin

2017-09-01

Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells. Characteristic of autophagosomes appeared after 24h treatment. Meanwhile, deregulation of Akt-mTOR pathway was also detected. When cultured in presence of autophagy inhibitors, autophagy and differentiation was reversed, and cell growth inhibition was also attenuated. Similar phenomenon could also be seen when beclin1 expression was down-regulated. Taken together, we concluded that LD Ara-C can induce autophagy in AML cells and appeared to play an important role in differentiation and death. Down-regulation of Akt-mTOR pathway is involved in these processes. We suggest that cytarabine-induced autophagy is not a pro-survival mechanism, but accounts for its antineoplastic effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrocortisone in culture protects the blast cells in acute myeloblastic leukemia from the lethal effects of cytosine arabinoside

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

Yang, G.S.; Wang, C.; Minkin, S.

The blast cells in acute myeloblastic leukemia (AML) respond to many of the same regulatory mechanisms that control normal hemopoiesis. These include the growth factors that bind to membrane receptors and steroid hormones or vitamins that have intracellular receptors. The authors report the effects in culture of the steroid glucocorticoid hydrocortisone on freshly explanted AML blasts from patients and on two continuous AML cell lines. Only small changes in clonogenic cell numbers in suspension cultures were seen in the presence of hydrocortisone. The most striking effect of the hormone was on the sensitivity of blasts cells to cytosine arabinoside (ara-C).more » In contrast to the response of AML blast cells to retinoic acid, a ligand for intracellular steroid receptors that sensitizes some blast populations to ara-C, hydrocortisone reduced the toxic effects of the drug. The protective action of hydrocortisone was not mediated through the cell cycle since exposure of blasts to hydrocortisone did not affect the percentage of cells in DNA synthesis as measured with the tritiated thymidine (3HTdR) suicide technique. The hydrocortisone effect could be demonstrated using a pulse (20 min) exposure protocol. Blasts pulsed with increasing specific activities of 3HTdR showed the usual response pattern with an initial loss in plating efficiency to about 50% of control, followed by a plateau, regardless of whether the cells had been exposed to hydrocortisone. Control blasts exposed to increasing ara-C concentrations gave very similar dose-response curves; in striking contrast, blast cells cultured in hydrocortisone, then pulsed with ara-C did not lose colony-forming ability even though the same population was sensitive to 3HTdR.« less

N-acetylcysteine supplementation reduces oxidative stress for cytosine arabinoside in rat model.

PubMed

Balci, Yasemin Isik; Acer, Semra; Yagci, Ramazan; Kucukatay, Vural; Sarbay, Hakan; Bozkurt, Kerem; Polat, Aziz

2017-02-01

Cytosine arabinoside (ARA-C) is a pyrimidine analog that may cause keratoconjunctivitis when used in high doses. The underlying mechanism may be the increased amounts of reactive oxygen radicals that may damage the DNA synthesis of corneal and conjunctival epithelial cells. Topical corticosteroids are one of the prophylactic treatments for keratoconjunctivitis induced by ARA-C. Forty Wistar-type albino rats were included in this study the rats were divided into four groups. The first group (Group 1) received only ARA-C, the second group (Group 2) received ARA-C and N-acetylcysteine (NAC), the third group (Group 3) received only NAC and the fourth group (Group 4) was the control group. The total oxidant status (TOS), the total antioxidant capacity and the oxidative stress index (OSI) measurements of the cornea and the conjunctiva were evaluated in these four groups. The mean TOS and OSI value was the highest in Group 1 and the lowest in Group 3. The differences in TOS and OSI values were statistically significant between Group 1 and Group 2. There are decreases in TOS and OSI values in rats which received ARA-C with NAC administration. NAC may have a protective effect on ARA-C-induced keratoconjunctivitis.

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27(Kip 1) in acute myeloblastic leukemia cells.

PubMed

Siitonen, Timo; Koistinen, Pirjo; Savolainen, Eeva-Riitta

2005-11-01

The effects of valproate and butyrate were investigated in an acute myeloblastic cell line (OCI/AML-2) on cytotoxicity, cell cycle profile and expression of cell cycle regulating proteins in the presence of cytarabine (Ara-C) and etoposide. As a single agent valproate and butyrate inhibited AML cell growth but did not significantly induce cell death. A dramatic increase in cytotoxicity was observed when combining valproate or butyrate with Ara-C, whereas, co-addition of them with etoposide had much smaller effect on cell death. Valproate induced a clear G1 phase arrest and up-regulated cyclin D1 expression in the presence of Ara-C and etoposide. In addition, valporate was able to block the Ara-C-induced down-regulation of p27(Kip1) expression but not that induced by etoposide.

Mechanism of interaction of the antileukemic drug cytosine arabinoside with aromatic peptides: role of sugar conformation and peptide backbone.

PubMed

Datta, G; Hosur, R V; Verma, N C; Khetrapal, C L; Gurnani, S

1989-01-01

Interaction of the antileukemic drugs, cytosine-arabinoside (Ara-C) and adenosine-arabinoside (Ara-A) and a structural analogue, cytidine, with aromatic dipeptides has been studied by fluorescence and NMR spectroscopy. Ara-C and cytidine bind tryptophanyl and histidyl dipeptides but not tyrosyl dipeptides, while Ara-A does not bind to any of them. Both studies indicate association involving stacking of aromatic moieties. NMR spectra also indicate a protonation of the histidine moiety by Ara-C. In case of cytidine, the chemical shifts observed on binding to His-Phe imply that the backbone protons of the dipeptide participate in the binding. The conformation of the sugar and the base seem to play a very important role in the binding phenomenon as three similar molecules, Ara-C, Ara-A and cytidine bind in totally different ways.

The linker region of AraC protein.

PubMed Central

Eustance, R J; Schleif, R F

1996-01-01

AraC protein, a transcriptional regulator of the L-arabinose operon in Escherichia coli, is dimeric. Each monomer consists of a domain for DNA binding plus transcription activation and a domain for dimerization plus arabinose binding. These are connected to one another by a linker region of at least 5 amino acids. Here we have addressed the question of whether any of the amino acids in the linker region play active, specific, and crucial structural roles or whether these amino acids merely serve as passive spacers between the functional domains. We found that all but one of the linker amino acids can be changed to other amino acids individually and in small groups without substantially affecting the ability of AraC protein to activate transcription when arabinose is present. When, however, the entire linker region is replaced with linker sequences from other proteins, the functioning of AraC is impaired. PMID:8955380

Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis.

PubMed

Boogerd, W; Moffie, D; Smets, L A

1990-02-01

A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.

Ash cloud aviation advisories

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

Sullivan, T.J.; Ellis, J.S.; Schalk, W.W.

1992-06-25

During the recent (12--22 June 1991) Mount Pinatubo volcano eruptions, the US Air Force Global Weather Central (AFGWC) requested assistance of the US Department of Energy`s Atmospheric Release Advisory Capability (ARAC) in creating volcanic ash cloud aviation advisories for the region of the Philippine Islands. Through application of its three-dimensional material transport and diffusion models using AFGWC meteorological analysis and forecast wind fields ARAC developed extensive analysis and 12-hourly forecast ash cloud position advisories extending to 48 hours for a period of five days. The advisories consisted of ``relative`` ash cloud concentrations in ten layers (surface-5,000 feet, 5,000--10,000 feet andmore » every 10,000 feet to 90,000 feet). The ash was represented as a log-normal size distribution of 10--200 {mu}m diameter solid particles. Size-dependent ``ashfall`` was simulated over time as the eruption clouds dispersed. Except for an internal experimental attempt to model one of the Mount Redoubt, Alaska, eruptions (12/89), ARAC had no prior experience in modeling volcanic eruption ash hazards. For the cataclysmic eruption of 15--16 June, the complex three-dimensional atmospheric structure of the region produced dramatically divergent ash cloud patterns. The large eruptions (> 7--10 km) produced ash plume clouds with strong westward transport over the South China Sea, Southeast Asia, India and beyond. The low-level eruptions (< 7 km) and quasi-steady-state venting produced a plume which generally dispersed to the north and east throughout the support period. Modeling the sequence of eruptions presented a unique challenge. Although the initial approach proved viable, further refinement is necessary and possible. A distinct need exists to quantify eruptions consistently such that ``relative`` ash concentrations relate to specific aviation hazard categories.« less

77 FR 27538 - Aviation Rulemaking Advisory Committee-Continuing a Task

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-10

... Committee--Continuing a Task AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of continuing a task assignment for the Aviation Rulemaking Advisory Committee (ARAC). SUMMARY: The FAA assigned the Aviation Rulemaking Advisory Committee (ARAC) a continuing task to provide advice and...

78 FR 49595 - Aviation Rulemaking Advisory Committee-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... the new ARAC activity and solicits membership for the Maintenance Reliability Program Working Group... establish the Maintenance Reliability Program Working Group. The working group will serve as staff to ARAC... programs. The Maintenance Reliability Program Working Group will provide advice and recommendations on the...

77 FR 10798 - Aviation Rulemaking Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... assigned to the Aviation Rulemaking Advisory Committee (ARAC) concerning all weather operations. This... Weather Operations Harmonization Working Group. Over the years since assigning this task to ARAC, the... the All Weather Operations Manual for ICAO. These efforts are important to the FAA and other civil...

Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia.

PubMed

Rathe, Susan K; Moriarity, Branden S; Stoltenberg, Christopher B; Kurata, Morito; Aumann, Natalie K; Rahrmann, Eric P; Bailey, Natashay J; Melrose, Ellen G; Beckmann, Dominic A; Liska, Chase R; Largaespada, David A

2014-08-13

The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and from RNA interference to gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying and quantifying the effects of gene changes on drug resistance. Here we describe the results from deep-sequencing of RNA derived from two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN based methods for accomplishing complete gene knockout (KO) in AML cells. We found protein modifying loss-of-function mutations in Dck in both Ara-C resistant cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC₅₀ of Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted in a significant increase in Ara-C sensitivity. This effort demonstrates the power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and verify genes associated with drug resistance.

ARAC--The Montreal Jewish General Hospital Alzheimer Risk Assessment Clinic.

PubMed

Schipper, Hyman M; Liberman, Adrienne; Kelner, Nora; Babins, Lennie; Fried, Lynda; Bilbul, Melanie; Goodman, Rachel

2011-07-01

In parallel with robust efforts world-wide to develop effective neuroprotection for established disease, resources are being mobilized to delineate risk factors and implement preventive measures in a concerted effort to forestall the anticipated Alzheimer disease (AD) epidemic. A review of heritable and 'acquired' dementia risk factors, many operating at midlife, is presented in a companion paper. In 2009, an Alzheimer Risk Assessment Clinic (ARAC) was established at the Jewish General Hospital (Montreal) to address the concerns increasingly being voiced by active middle-aged individuals at risk for AD. A positive family history of AD and/or perceived changes in personal cognitive function (predominantly short-term memory) are main reasons for referral. The primary objectives of ARAC are to (i) ascertain, inform and mitigate the risks of developing AD in cognitively-healthy persons aged 40-65 based on best available medical and epidemiological evidence, (ii) conduct scientific research on midlife dementia risk and prevention in this population and (iii) provide instruction in dementia risk assessment and management to health professionals, clinical/research fellows, medical residents and students. ARAC infrastructure, evaluation protocol, risk profile classification scheme, interventions, knowledge dissemination program, case vignettes, and seminal research projects are described. It is hoped that ARAC and similar initiatives will help prevent or delay dementia by innovating effective interventions based on increasingly nuanced estimation of modifiable AD risk in presymptomatic persons.

Purine Analog-Like Properties of Bendamustine Underlie Rapid Activation of DNA Damage Response and Synergistic Effects with Pyrimidine Analogues in Lymphoid Malignancies

PubMed Central

Hiraoka, Nobuya; Kikuchi, Jiro; Yamauchi, Takahiro; Koyama, Daisuke; Wada, Taeko; Uesawa, Mitsuyo; Akutsu, Miyuki; Mori, Shigehisa; Nakamura, Yuichi; Ueda, Takanori; Kano, Yasuhiko; Furukawa, Yusuke

2014-01-01

Bendamustine has shown considerable clinical activity against indolent lymphoid malignancies as a single agent or in combination with rituximab, but combination with additional anti-cancer drugs may be required for refractory and/or relapsed cases as well as other intractable tumors. In this study, we attempted to determine suitable anti-cancer drugs to be combined with bendamustine for the treatment of mantle cell lymphoma, diffuse large B-cell lymphoma, aggressive lymphomas and multiple myeloma, all of which are relatively resistant to this drug, and investigated the mechanisms underlying synergism. Isobologram analysis revealed that bendamustine had synergistic effects with alkylating agents (4-hydroperoxy-cyclophosphamide, chlorambucil and melphalan) and pyrimidine analogues (cytosine arabinoside, gemcitabine and decitabine) in HBL-2, B104, Namalwa and U266 cell lines, which represent the above entities respectively. In cell cycle analysis, bendamustine induced late S-phase arrest, which was enhanced by 4-hydroperoxy-cyclophosphamide, and potentiated early S-phase arrest by cytosine arabinoside (Ara-C), followed by a robust increase in the size of sub-G1 fractions. Bendamustine was able to elicit DNA damage response and subsequent apoptosis faster and with shorter exposure than other alkylating agents due to rapid intracellular incorporation via equilibrative nucleoside transporters (ENTs). Furthermore, bendamustine increased the expression of ENT1 at both mRNA and protein levels and enhanced the uptake of Ara-C and subsequent increase in Ara-C triphosphate (Ara-CTP) in HBL-2 cells to an extent comparable with the purine analog fludarabine. These purine analog-like properties of bendamustine may underlie favorable combinations with other alkylators and pyrimidine analogues. Our findings may provide a theoretical basis for the development of more effective bendamustine-based combination therapies. PMID:24626203

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

PubMed Central

Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

2013-01-01

Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)—we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3′-ends. We also show that Tdp1−/− cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1−/− cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs. PMID:23775789

Program report for FY 1984 and 1985 Atmospheric and Geophysical Sciences Division of the Physics Department

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

Knox, J.B.; MacCracken, M.C.; Dickerson, M.H.

1986-08-01

This annual report for the Atmospheric and Geophysical Sciences Division (G-Division) summarizes the activities and highlights of the past three years, with emphasis on significant research findings in two major program areas: the Atmospheric Release Advisory Capability (ARAC), with its recent involvement in assessing the effects of the Chernobyl reactor accident, and new findings on the environmental consequences of nuclear war. The technical highlights of the many other research projects are also briefly reported, along with the Division's organization, budget, and publications.

Role of ABCB5 P-Glycoprotein in Breast Cancer Multidrug Resistance

DTIC Science & Technology

2005-09-01

Hydroxyurea Doxorubicin Porfiromycin Mechlorethamine Fluorodopan Mitomycin Cytarabine (araC) Dianhydrogalactitol Gemcitabine Thiotepa N-N-Dibenzyl-daunomycin...0.0196 Mitomycin 0.4173 0.0318 Cytarabine (araC) 0.4163 0.0288 Dianhydrogalactitol 0.4105 0.0354 Gemcitabine 0.4088 0.0302 Thiotepa 0.4015 0.0232

78 FR 24289 - Aviation Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group (ATSTWG) AGENCY... FAA will post all comments it receives, without change, to http://www.regulations.gov , including any... several draft documents developed by the Airman Testing Standards and Training Working Group. The...

75 FR 55393 - Aviation Rulemaking Advisory Committee Meeting on Transport Airplane and Engine Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

... Committee Meeting on Transport Airplane and Engine Issues AGENCY: Federal Aviation Administration (FAA), DOT... Rulemaking Advisory Committee (ARAC) to discuss transport airplane and engine (TAE) issues. DATES: The...: Opening Remarks, Review Agenda and Minutes. FAA Report. ARAC Executive Committee Report. Transport Canada...

78 FR 57672 - Aviation Rulemaking Advisory Committee Meeting on Transport Airplane and Engine Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

... Committee Meeting on Transport Airplane and Engine Issues AGENCY: Federal Aviation Administration (FAA), DOT... Rulemaking Advisory Committee (ARAC) Transport Airplane and Engine (TAE) Subcommittee to discuss TAE issues... meeting is as follows: Opening Remarks, Review Agenda and Minutes FAA Report ARAC Report Transport Canada...

A Report of the Joint Development of a Prototype Communications Link to Share Nuclear Accident Dispersion and Dose Assessment Modeling Products Between JAERI/WSPEEDI and LLNL/NARAC

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

Sullivan, T J; Belles, R D; Ellis, J S

2001-05-01

In June of 1997, under an umbrella Memorandum of Understanding between the Japan Atomic Energy Research Institute (JAERI) and the U.S. Department of Energy (US/DOE) concerning matters of nuclear research and development, a Specific Memorandum of Agreement (SMA) entitled ''A Collaborative Programme of Development of a Prototype Communication Link to Share Atmospheric Dispersion and Dose Assessment Modelling Products'' was signed. This SMA formalized an informal collaborative exchange between the DOE's Lawrence Livermore National Laboratory (LLNL) Atmospheric Release Advisory Capability (ARAC) center and the Japan Atomic Energy Research Institute (JAERI) Worldwide System for Prediction of Environmental Emergency Dose Information (WSPEEDI). Themore » intended objective of this agreement was to explore various modes of information exchange, beyond facsimile transmission, which could provide for the quick exchange of information between two major nuclear emergency dose assessment and prediction national centers to provide consistency checks and data exchange before public release of their calculations. The extreme sensitivity of the general public to any nuclear accident information has been a strong motivation to seek peer preview prior to public release. Other intended objectives of this work are the development of an affordable/accessible system for distribution of prediction results to other countries having no prediction capabilities and utilization of the link for collaboration studies. To fulfill the objectives of this project JAERI and LLNL scientists determined to assess the evolving Internet and rapidly emerging communications application software. Our timing was a little early in 1997-1998 but nonetheless a few candidate software packages were found, evaluated and a selection was made for initial test and evaluation. Subsequently several new candidate software packages have arrived, albeit with limitations. This report outlines the ARAC and JAERI emergency response assessment systems, describes the prototype communications protocol system established and the tools evaluated in that process. Three real-time applications of the information exchange protocol and lessons learned are discussed and then some conclusions and future plans are presented.« less

77 FR 56251 - Aviation Rulemaking Advisory Committee (ARAC); New Task Assignment for the ARAC: Establishment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... with the Airman Certification Standards documents; and to propose knowledge test item bank questions... ensure that knowledge test item bank questions are consistent with both the Airman Certification... knowledge and risk management into each Area of Operation in the current Practical Test Standards documents...

75 FR 52807 - Aviation Rulemaking Advisory Committee; Transport Airplane and Engine Issues-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

...'s Transport Airplane and Engine Issues and has established a new Materials Flammability Working... International Aircraft Materials Fire Test Working Group. The working group is sponsored by the FAA's William J... implementation. FAA will provide ARAC with the proposed approach. The ARAC working group is expected to produce a...

78 FR 50138 - Aviation Rulemaking Advisory Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... Standard Time. Arrange oral presentations by September 12, 2013. ADDRESSES: The meeting will take place at... Act (5 U.S.C. App. 2), we are giving notice of a meeting of the ARAC taking place on September 19... Agenda includes: 1. Recommendation Report a. Airman Testing Standards and Training Working Group (ARAC) 2...

Effects of early chemotherapeutic treatment on learning in adolescent mice: implications for cognitive impairment and remediation in childhood cancer survivors.

PubMed

Bisen-Hersh, Emily B; Hineline, Philip N; Walker, Ellen A

2013-06-01

Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40% to 70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Preweanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days after treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Significant impairment in acquisition and retention over both short (1 hour) and long (24 hours) intervals, as measured by autoshaping and novel object recognition tasks, was found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Findings are consistent with those from clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. ©2013 AACR

JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C).

PubMed

Shami, Paul J; Maciag, Anna E; Eddington, Jordan K; Udupi, Vidya; Kosak, Ken M; Saavedra, Joseph E; Keefer, Larry K

2009-11-01

We have designed prodrugs that release nitric oxide (NO) on metabolism by glutathione S-transferases (GST). This design exploits the upregulation of GST in acute myeloid leukemia (AML) cells. O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-leukemic activity. HL-60 myeloid leukemia cells were used for in vitro studies of the combination of JS-K with daunorubicin (DAUNO), cytarabine (ARA-C) or etoposide (ETOP) using the median effect method to determine synergistic, antagonistic, or additive effects. Combinations of JS-K added simultaneously, 2h before or 2h after the other compounds were used. JS-K and DAUNO were antagonistic in all three drug sequences. JS-K and ETOP were also antagonistic but to a lesser degree. JS-K and ARA-C showed strong synergy. The combination index at the 50% fraction affected was 0.37+/-0.23, 0.24+/-0.27, and 0.15+/-0.11 for simultaneous, JS-K first and ARA-C first additions, respectively. JS-K by itself induced DNA strand breaks at relatively high concentrations. However, at submicromolar concentrations, it significantly augmented ARA-C-induced DNA strand breaks. NMR spectroscopy revealed no evidence of chemical interaction between JS-K and the other chemotherapeutic agents. We conclude that ARA-C and JS-K have synergistic anti-leukemic activity and warrant further exploration in combination.

Effects of Early Chemotherapeutic Treatment on Learning in Adolescent Mice: Implications for Cognitive Impairment and Remediation in Childhood Cancer Survivors

PubMed Central

Bisen-Hersh, Emily B.; Hineline, Philip N.; Walker, Ellen A.

2013-01-01

Purpose Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40-70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Experimental Design Pre-weanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days following treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Results Significant impairment in acquisition and retention over both short (1h) and long (24h) intervals, as measured by autoshaping and novel object recognition tasks, were found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Conclusions Findings are consistent with clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy treatment. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. PMID:23596103

Yersinia pestis with regulated delayed attenuation as a vaccine candidate to induce protective immunity against plague.

PubMed

Sun, Wei; Roland, Kenneth L; Kuang, Xiaoying; Branger, Christine G; Curtiss, Roy

2010-03-01

Two mutant strains of Yersinia pestis KIM5+, a Deltacrp mutant and a mutant with arabinose-dependent regulated delayed-shutoff crp expression (araC P(BAD) crp), were constructed, characterized in vitro, and evaluated for virulence, immunogenicity, and protective efficacy in mice. Both strains were highly attenuated by the subcutaneous (s.c.) route. The 50% lethal doses (LD(50)s) of the Deltacrp and araC P(BAD) crp mutants were approximately 1,000,000-fold and 10,000-fold higher than those of Y. pestis KIM5+, respectively, indicating that both strains were highly attenuated. Mice vaccinated s.c. with 3.8 x 10(7) CFU of the Deltacrp mutant developed high anti-Y. pestis and anti-LcrV serum IgG titers, both with a strong Th2 bias, and induced protective immunity against subcutaneous challenge with virulent Y. pestis (80% survival) but no protection against pulmonary challenge. Mice vaccinated with 3.0 x 10(4) CFU of the araC P(BAD) crp mutant also developed high anti-Y. pestis and anti-LcrV serum IgG titers but with a more balanced Th1/Th2 response. This strain induced complete protection against s.c. challenge and partial protection (70% survival) against pulmonary challenge. Our results demonstrate that arabinose-dependent regulated crp expression is an effective strategy to attenuate Y. pestis while retaining strong immunogenicity, leading to protection against the pneumonic and bubonic forms of plague.

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study

PubMed Central

Schlegel, U; Pels, H; Glasmacher, A; Kleinschmidt, R; Schmidt-Wolf, I; Helmstaedter, C; Fliessbach, K; Deckert, M; Van Roost, D; Fimmers, R; Bode, U; Klockgether, T

2001-01-01

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL).
 From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C.
 Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse).
 In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70years.

 PMID:11413277

Cafestol, a diterpene molecule found in coffee, induces leukemia cell death.

PubMed

Lima, Cauê S; Spindola, Daniel G; Bechara, Alexandre; Garcia, Daniel M; Palmeira-Dos-Santos, Caroline; Peixoto-da-Silva, Janaina; Erustes, Adolfo G; Michelin, Luis F G; Pereira, Gustavo J S; Smaili, Soraya S; Paredes-Gamero, Edgar; Calgarotto, Andrana K; Oliveira, Carlos R; Bincoletto, Claudia

2017-08-01

To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

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

Shi, Lin; Song, Quansheng; Zhang, Yingmei

Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosismore » rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.« less

Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1985. Volume 2,

DTIC Science & Technology

1985-10-01

Objective(s): To study the feasibility of cytosine arabinoside (ara-C), used in high dosage in conjunction with fractionated total body irradiation... Using High Dose Ara-C 335 in Adult Acute Leukemia and Chronic Granulocytic Leukemia in Blastic Crisis, Phase III. (0) SWOG 8328 Evaluation of...Fludarabine Phosphate in Cervical Cancer, 336 Phase II. (0) SWOG 8360 Use of the Surgically Implanted "Infusaid" Pump for Ambula- 337 tory Ottpatient Hepatic

Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

PubMed

Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

2016-11-20

Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

Kinetic study of the scavenging reaction of the aroxyl radical by seven kinds of rice bran extracts in ethanol solution. Development of an aroxyl radical absorption capacity (ARAC) assay method.

PubMed

Mukai, Kazuo; Ouchi, Aya; Abe, Takumi; Murata, Kazumasa; Nakagawa, Kiyotaka; Miyazawa, Teruo

2014-12-10

Recently, a new assay method that can quantify the aroxyl radical (ArO•) absorption capacity (ARAC) of antioxidants (AOHs) was proposed. In the present work, the second-order rate constants (ks(Extract)) and ARAC values for the reaction of ArO• with seven kinds of rice bran extracts 1-7, which contain different concentrations of α-, β-, γ-, and δ-tocopherols and -tocotrienols (α-, β-, γ-, and δ-Tocs and -Toc-3s) and γ-oryzanol, were measured in ethanol at 25 °C using stopped-flow spectrophotometry. The ks(Extract) value (1.26 × 10(-2) M(-1) s(-1)) of Nipponbare (extract 1) with the highest activity was 1.5 times larger than that (8.29 × 10(-3)) of Milyang-23 (extract 7) with the lowest activity. The concentrations (in mg/100 g) of α-, β-, γ-, and δ-Tocs and -Toc-3s and γ-oryzanol found in the seven extracts 1-7 were determined using HPLC-MS/MS and UV-vis absorption spectroscopy, respectively. From the results, it has been clarified that the ArO•-scavenging rates (ks(Extract)) (that is, the relative ARAC value) obtained for the seven extracts 1-7 may be approximately explained as the sum of the product {Σ ks(AOH-i) [AOH-i]/10(5)} of the rate constant (ks(AOH-i)) and the concentration ([AOH-i]/10(5)) of AOH-i (Tocs, Toc-3s, and γ-oryzanol) included in rice bran extracts. The contribution of γ-oryzanol to the ks(Extract) value was estimated to be between 3.0-4.7% for each extract. Taken together, these results suggest that the ARAC assay method is applicable to general food extracts.

SPARC ectopic overexpression inhibits growth and promotes programmed cell death in acute myeloid leukemia transformed from myelodysplastic syndrome cells, alone and in combination with Ara-C treatment.

PubMed

Nian, Qing; Chi, Jianxiang; Xiao, Qing; Wei, Chunmei; Costeas, Paul; Yang, Zesong; Liu, Lin; Wang, Li

2015-09-01

Secreted protein acidic and rich in cysteine (SPARC) has a complex and pleiotropic biological role in cell life during disease. The role of SPARC in myelodysplastic syndrome (MDS) is not yet fully understood. In the present study, we investigated the role of SPARC protein overproduction in the proliferation and apoptosis of SKM-1 cells, an acute myeloid leukemia cell line transformed from MDS. SKM-1 cells were infected with the pGC-GV-SPARC vector. The cells were then assessed for proliferation and cell death following treatment with low-dose cytosine arabinoside (Ara‑C). The microarray analysis results revealed that samples from SPARC‑overexpressed cells compared to SPARC protein, in SKM-1 cells led to proliferation inhibition and promoted programmed cell death and these effects were greater when treated with Ara-C. The mRNA and protein expression levels of SPARC were detected by SPARC overexpression in cells treated with Ara-C resulting in a significant upregulation of the mixed lineage kinase domain-like (MLKL) gene expression and five other genes. The results showed that the necrotic signaling pathway may play a role when the two conditions were combined via the upregulation of the MLKL protein. MLKL upregulation in SPARC overexpressed cells treated with Ara-C, indicates necrosis as a possible cell death process for the SKM-1 cells under these stringent conditions.

Curative chemotherapy for acute myeloid leukemia: the development of high-dose ara-C from the laboratory to bedside.

PubMed

Capizzi, R L

1996-01-01

In the bench to bedside development of drugs to treat patients with cancer, the common guide to dose and schedule selection is toxicity to normal organs patterned after the preclinical profile of the drug. An understanding of the cellular pharmacology of the drug and specifically the cellular targets linked to the drug's effect is of substantial value in assisting the clinical investigator in selecting the proper dose and schedule of drug administration. The clinical development of ara-C for the treatment of acute myeloid leukemia (AML) provides a useful paradigm for the study of this process. An understanding of the cellular pharmacology, cytokinetics and pharmacokinetics of ara-C in leukemic mice showed substantial schedule-dependency. Exposure to high doses for a short duration (C x t) resulted in a palliative therapeutic outcome. In marked contrast, exposure to lower doses for a protracted period (c x T) was curative. Clinical use of ara-C in patients with AML patterned after the murine experience, c x T approach, has been of limited benefit in terms of long-term disease-free survival. Studies with human leukemia blasts from patients have shown that for the majority of patients, the initial rate-limiting step is membrane transport, the characteristics of which are substantially affected by extracellular drug concentration (dose). This pharmacologic impediment is eliminated with the blood levels attained during the infusion of gram doses (1-3 gm/m2) of the drug (high-dose ara-C, HiDaC) for shorter periods of time, a C x t approach. Clinical confirmation of these pharmacologic observations is evident in the therapeutic efficacy of HiDaC in patients with relapsed or SDaC-refractory acute leukemia. This is further emphasized by the significantly improved leukemia-free survival of patients with AML treated with HiDaC intensification during remission compared to those patients treated with milligram doses typical of SDaC protocols. Thus, the identification and monitoring of important parameters of drug action in tumors during the course of a clinical trial can be of substantial assistance in optimizing drug dose and schedule so as to attain the best therapeutic index.

HPLC-MS/MS method for the simultaneous determination of MB07133 and its metabolites, cytarabine and arabinofuranosyluracil, in rat plasma.

PubMed

Wang, Dan; Xiao, Qingqing; Yang, Wanqiu; Qian, Wei; Yang, Jin

2016-02-20

MB07133 is an intravenously administered cytarabine mononucleotide (araCMP) prodrug, for the treatment of hepatocellular carcinoma (HCC). A simple, selective and sensitive HPLC-MS/MS method using high pressure liquid chromatography (HPLC) coupled to triple-quadrupole mass spectrometer, was developed and validated for the detection of prodrug MB07133 and its metabolites, cytarabine (araC) and arabinofuranosyluracil (araU) in rat plasma. Protein precipitation using 3% trichloroacetic acid (TCA) was employed to extract analytes from 100μL rat plasma. Adequate separation of araC and araU from their endogenous compounds was achieved on the Synergi(®) fusion-RP column (150mm×4.6mm, 4μm) by a gradient-elution with a mobile phase consisting of ammonium formate (1mM) and methanol at a flow rate of 1mL/min. Multiple reaction monitoring mode (MRM) was applied in the detection of MB07133, araC, araU and Ganciclovir (internal standard) with ion pairs 441.2/330.2, 244.2/112.2, 245.2/113.2 and 256.1/152.2, respectively. The assays were validated with respect to specificity, linearity (100-50000ng/mL for MB07133, 2-1000ng/mL for araC and araU), accuracy and precision, extraction recovery, matrix effect and stability. The validated method has been successfully applied to an intravenous bolus pharmacokinetic study of MB07133 in male Sprague-Dawley rats (18mg/kg i.v.). Copyright © 2015 Elsevier B.V. All rights reserved.

Synergy of sequential administration of a deglycosylated ricin A chain-containing combined anti-CD19 and anti-CD22 immunotoxin (Combotox) and cytarabine in a murine model of advanced acute lymphoblastic leukemia

PubMed Central

Barta, Stefan K.; Zou, Yiyu; Schindler, John; Shenoy, Niraj; Bhagat, Tushar D.; Steidl, Ulrich; Verma, Amit

2013-01-01

The outcome for patients with refractory or relapsed acute lymphoblastic leukemia (ALL) treated with conventional therapy is poor. Immunoconjugates present a novel approach and have recently been shown to have efficacy in this setting. Combotox is a mixture of two ricin-conjugated monoclonal antibodies (RFB4 and HD37) directed against CD19 and CD22, respectively, and has shown activity in pediatric and adult ALL. We created a murine xenograft model of advanced ALL using the NALM/6 cell line to explore whether the combination of Combotox with the cytotoxic agent cytarabine (Ara-C) results in better outcomes. In our model the combination of both low- and high-dose Combotox and Ara-C resulted in significantly longer median survival. Sequential administration of Ara-C and Combotox, however, was shown to be superior to concurrent administration. These findings have led to a phase I clinical trial exploring this combination in adults with relapsed or refractory B-lineage ALL (ClinicalTrials.gov identifier NCT01408160). PMID:22448921

Paracetamol and cytarabine binding competition in high affinity binding sites of transporting protein

NASA Astrophysics Data System (ADS)

Sułkowska, A.; Bojko, B.; Równicka, J.; Sułkowski, W. W.

2006-07-01

Paracetamol (acetaminophen, AA) the most popular analgesic drug is commonly used in the treatment of pain in patients suffering from cancer. In our studies, we evaluated the competition in binding with serum albumin between paracetamol (AA) and cytarabine, antyleukemic drug (araC). The presence of one drug can alter the binding affinity of albumin towards the second one. Such interaction can result in changing of the free fraction of the one of these drugs in blood. Two spectroscopic methods were used to determine high affinity binding sites and the competition of the drugs. Basing on the change of the serum albumin fluorescence in the presence of either of the drugs the quenching ( KQ) constants for the araC-BSA and AA-BSA systems were calculated. Analysis of UV difference spectra allowed us to describe the changes in drug-protein complexes (araC-albumin and AA-albumin) induced by the presence of the second drug (AA and araC, respectively). The mechanism of competition between araC and AA has been proposed.

Stereoselective synthesis of the 5'-hydroxy-5'-phosphonate derivatives of cytidine and cytosine arabinoside.

PubMed

Chen, Xuemei; Wiemer, Andrew J; Hohl, Raymond J; Wiemer, David F

2002-12-27

Both the (R)- and (S)-5'-hydroxy 5'-phosphonate derivatives of cytidine and cytosine arabinoside (ara-C) have been prepared via phosphite addition or a Lewis acid mediated hydrophosphonylation of appropriately protected 5'-nucleoside aldehydes. Phosphite addition to a cytosine aldehyde protected as the 2',3'-acetonide gave predominately the 5'R isomer, while phosphite addition to the corresponding 2',3'-bis TBS derivative favored the 5'S stereochemistry. In contrast, phosphite addition to the 2',3'-bis TBS protected aldehyde derived from ara-C gave only the 5'R adduct. However, TiCl(4)-mediated hydrophosphonylation of the same ara-C aldehyde favored the 5'S stereoisomer by a 2:1 ratio. Once all four of the diastereomers were in hand, the stereochemistry of these compounds could be assigned based on their spectral data or that obtained from their O-methyl mandelate derivatives. After hydrolysis of the phosphonate esters and various protecting groups, the four alpha-hydroxy phosphonic acids were tested for their ability to serve as substrates for the enzyme nucleoside monophosphate kinase and for their toxicity to K562 cells.

Supplementation with RRR- or all-rac-α-Tocopherol Differentially Affects the α-Tocopherol Stereoisomer Profile in the Milk and Plasma of Lactating Women.

PubMed

Gaur, Shashank; Kuchan, Matthew J; Lai, Chron-Si; Jensen, Soren K; Sherry, Christina L

2017-07-01

Background: The naturally occurring α-tocopherol stereoisomer RRR- α-tocopherol is known to be more bioactive than synthetic α-tocopherol ( all-rac -α-tocopherol). However, the influence of this difference on the α-tocopherol stereoisomer profile of human milk is not understood. Objective: We investigated whether supplemental RRR- α-tocopherol or all-rac -α-tocopherol differentially affected the distribution of α-tocopherol stereoisomers in milk and plasma from lactating women. Methods: Eighty-nine lactating women aged 19-40 y and with a body mass index (in kg/m 2 ) ≤30 were randomly assigned at 4-6 wk postpartum to receive a daily supplement containing 45.5 mg all-rac -α-tocopherol acetate (ARAC), 22.8 mg all-rac -α-tocopherol acetate + 20.1 mg RRR -α-tocopherol (MIX), or 40.2 mg RRR- α-tocopherol (RRR). Milk and plasma were analyzed for α-tocopherol structural isomers and α-tocopherol stereoisomers at baseline and after 6 wk supplementation with the use of chiral HPLC. Results: There were no significant treatment group or time-dependent changes in milk or plasma α, γ, or δ-tocopherol. RRR- α-tocopherol was the most abundant stereoisomer in both milk and plasma in each group. Supplementation changed both milk and plasma percentage RRR- α-tocopherol (RRR > MIX > ARAC) ( P < 0.05) and percentage non- RRR- α-tocopherol (ARAC > MIX > RRR) ( P < 0.05). In the RRR group, percentage RRR- α-tocopherol increased in milk (mean ± SEM: 78% ± 2.3% compared with 82% ± 1.7%) ( P < 0.05) and plasma (mean ± SEM: 77% ± 1.8% compared with 87% ± 1%) ( P < 0.05). In contrast, the percentage RRR- α-tocopherol decreased in the MIX and ARAC groups (MIX, P < 0.05; ARAC, P < 0.0001), and percentage non- RRR- α-tocopherol stereoisomers increased (MIX, P < 0.05; ARAC, P < 0.0001) commensurate with an accumulation of 2S- α-tocopherol stereoisomers ( P < 0.05) in both milk and plasma. Milk and plasma RRR- α-tocopherol was positively correlated at baseline ( r = 0.67; P < 0.0001) and 6 wk ( r = 0.80; P < 0.0001). Conclusion: The α-tocopherol supplementation strategy differentially affected the α-tocopherol milk and plasma stereoisomer profile in lactating women. RRR- α-tocopherol increased milk and plasma percentage RRR- α-tocopherol, whereas all-rac -α-tocopherol acetate reduced these percentages. Because RRR- α-tocopherol is the most bioactive stereoisomer, investigating the impact of supplement-driven changes in the milk α-tocopherol stereoisomer profile on the α-tocopherol status of breastfed infants is warranted. © 2017 American Society for Nutrition.

Differences in the Mechanism of the Allosteric L-Rhamnose Responses of the AraC/XylS Family Transcription Activators RhaS and RhaR

PubMed Central

Kolin, Ana; Balasubramaniam, Vinitha; Skredenske, Jeff; Wickstrum, Jason; Egan, Susan M.

2008-01-01

SUMMARY Proteins in the largest subset of AraC/XylS family transcription activators, including RhaS and RhaR, have C-terminal domains (CTDs) that mediate DNA-binding and transcription activation, and N-terminal domains (NTDs) that mediate dimerization and effector binding. The mechanism of the allosteric effector response in this family has been identified only for AraC. Here, we investigated the mechanism by which RhaS and RhaR respond to their effector, L-rhamnose. Unlike AraC, N-terminal truncations suggested that RhaS and RhaR don’t use an N-terminal arm to inhibit activity in the absence of effector. We used random mutagenesis to isolate RhaS and RhaR variants with enhanced activation in the absence of L-rhamnose. NTD substitutions largely clustered around the predicted L-rhamnose-binding pockets, suggesting that they mimic the structural outcome of effector binding to the wild-type proteins. RhaS-CTD substitutions clustered in the first HTH motif, and suggested that L-rhamnose induces improved DNA binding. In contrast, RhaR-CTD substitutions clustered at a single residue in the second HTH motif, at a position consistent with improved RNAP contacts. We propose separate allosteric mechanisms for the two proteins: Without L-rhamnose, RhaS doesn’t effectively bind DNA while RhaR doesn’t effectively contact RNAP. Upon L-rhamnose binding, both proteins undergo structural changes that enable transcription activation. PMID:18366439

Neurodegenerative Central Nervous System Langerhans Cell Histiocytosis and Coincident Hydrocephalus: Treated with Vincristine/Cytosine Arabinoside

PubMed Central

Allen, Carl E.; Flores, Ricardo; Rauch, Ronald; Dauser, Robert; Murray, Jeffrey C.; Puccetti, Diane; Hsu, David A.; Sondel, Paul; Hetherington, Maxine; Goldman, Stan; McClain, Kenneth L.

2012-01-01

Background Central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) include mass lesions and a neurodegenerative (ND) syndrome with ataxia, dysarthria, dysmetria, learning and behavior difficulties and/or characteristic changes on brain MRIs. Hydrocephalus has rarely been reported in LCH. LCH lesions of the orbit, mastoid and temporal bones (“CNS-Risk” lesions) and diabetes insipidus predispose patients to ND-CNS-LCH. Treatment options have been limited and only a case series using trans-retinoic acid (ATRA) and intravenous immunoglobulin (IVIG) have been published. Methods We have used cytosine arabinoside (ARA-C) with or without vincristine to treat 8 patients with ND-CNS LCH. Patients:7 male children and one young adult male with clinical and radiologic ND- CNS-LCH were treated with a regimen of vincristine 1.5 mg/m2 on day 1 and ARA-C 100 mg/m2 daily for 5 days or ARA-C alone monthly for 4–19 months. Seven patients were evaluated with an ataxia rating scale (ARS) and all with serial MRIs of the brain. Results Five of 7 patients had decreases in their ARS scores and/or decreased T2 hyperintense lesions on MRI images. Grade 2 neutropenia was the most frequent adverse event. Vincristine-associated neuropathy occurred in two patients. Hydrocephalus caused symptoms and signs that confounded the diagnosis and management of ND-CNS-LCH in all 4 patients affected with both. Conclusions Subtle changes in neurologic function may be complicated by hydrocephalus. Vcr/ARA-C or ARA-C were an effective therapies for some ND-CNS LCH patients. A clinical trial using this and possibly other modalities such as IVIG or ATRA should be done. PMID:19908293

Measurement of myeloid maturation by flow cytochemistry in HL-60 leukemia: esterase is inducible, myeloperoxidase is not.

PubMed

Ross, D W

1986-05-01

The phenomenon of leukemic cell maturation requires a measurement of myeloid maturation to understand the process and to exploit it as a means of therapy for leukemia. The HL-60 leukemic cell line was used as a model of induced leukemic cell maturation in order to develop a method of quantitating granulocytic and monocytic maturation in response to drug therapy. An automated flow cytochemistry system (Hemalog-D) was employed to measure mean cell volume, myeloperoxidase (MPO), and nonspecific esterase (NSE). For granulocytic maturation induced by vitamin A or DMSO, MPO and cell volume decreased by 50%, maintaining a constant mean cellular MPO concentration throughout maturation from promyelocyte to neutrophil-like forms. For monocytic maturation induced by low-dose ARA-c, the mean NSE increased substantially, while cell volume remained constant. Unlike MPO concentration, NSE was truly inducible and thus a useful quantitative measure of maturation caused by low-dose ARA-c. Flow cytochemistry and cytofluorometry may be developed to allow for quantitative monitoring of therapeutic trials of induced maturation in human leukemias. However, this will require adapting these techniques to the complexity of human leukemias in vivo, and the necessity of handling heterogeneous populations encountered in bone marrow samples.

Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group.

PubMed

Wierzbowska, Agnieszka; Robak, Tadeusz; Pluta, Agnieszka; Wawrzyniak, Ewa; Cebula, Barbara; Hołowiecki, Jerzy; Kyrcz-Krzemień, Sławomira; Grosicki, Sebastian; Giebel, Sebastian; Skotnicki, Aleksander B; Piatkowska-Jakubas, Beata; Kuliczkowski, Kazimierz; Kiełbiński, Marek; Zawilska, Krystyna; Kłoczko, Janusz; Wrzesień-Kuś, Agata

2008-02-01

Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients. The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA. One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated with decreased probability of DFS. We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.

Monitoring tectonic uplift and paleoenvironmental reconstruction for marine terraces near Maǧaracik and Samandaǧ, Hatay Province, Turkey.

PubMed

Florentin, Jonathan A; Blackwell, Bonnie A B; Tüysüz, Okan; Tarı, Ufuk; Can Genç, Ş; İmren, Caner; Mo, Shirley; Huang, Yiwen E W; Blickstein, Joel I B; Skinner, Anne R; Kim, Maria

2014-06-01

Near Hatay, the Antakya-Samandağ-Cyprus Fault (ASCF), East Anatolian and Dead Sea Fault Zones, the large faults that form the edges of the African, Anatolian, Cyprus and Arabian Plates, all produce large earthquakes, which have decimated Hatay repeatedly. Near Samandağ, Hatay, differential vertical displacement on the ASCF has uplifted the southeastern side relative to northwestern side, producing large fault scarps that parallel the Asi (Orontes) River. Tectonic uplift coupled with Quaternary sealevel fluctuations has produced several stacked marine terraces stranded above current sealevel. This study dated 24 mollusc samples from 10 outcrops on six marine terraces near Samandağ electron spin resonance (ESR). Ages were calculated using time-averaged and volumetrically averaged external dose rates, modelled by assuming typical water depths for the individual species and sediment thicknesses estimated from geological criteria. Uplift rates were then calculated for each fault block. At all the Mağaracık terraces, the dates suggest that many shells were likely reworked. On the 30 m terrace at Mağaracık IV (UTM 766588-3999880), Lithophagus burrows with in situ shells cross the unconformity. One such shell dated to 62 ± 6 ka, setting the minimum possible age for the terrace. For all the Mağaracık terraces at ∼30 m above mean sealevel (amsl), the youngest ages for the reworked shells, which averaged 60 ± 3 ka for six separate analyses, sets the maximum possible age for this unit. Thus, the terrace must date to 60-62 ± 3 ka, at the MIS 3/4 boundary when temperatures and sealevels were fluctuating rapidly. Older units dating to MIS 7, 6, and 5 likely were being eroded to supply some fossils found in this terrace. At Mağaracık Dump (UTM 765391-4001048), ∼103 m amsl, Ostrea and other shells were found cemented in growth position to the limestone boulders outcropping there <2.0 m above a wave-eroded notch. If the oysters grew at the same time as the wave-cut notch and the related terrace, the date, 91 ± 13 ka, for the oysters, this fault block has been uplifted at 1.19 ± 0.15 m ky(-1), since MIS 5c. At Samandağ Kurt Stream at 38 m amsl, molluscs were deposited fine sandy gravel, which was likely formed in a large tidal channel. Four molluscs averaged 116 ± 5 ka. If these molluscs have not been reworked, this fault block has uplifted at 0.34 ± 0.05 m ky(-1) since the MIS 5d/5e boundary. The differences in these uplift rates suggests that at least one, and possibly two, hitherto undiscovered faults may separate the Mağaracık Dump site from the other Mağaracık sites and from the Samandağ Kurt Stream site. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synergistic inhibition in vivo of bone marrow myeloid progenitors by myelosuppressive chemokines and chemokine-accelerated recovery of progenitors after treatment of mice with Ara-C.

PubMed

Broxmeyer, Hal E; Pelus, Louis M; Kim, Chang H; Hangoc, Giao; Cooper, Scott; Hromas, Robert

2006-08-01

Selected chemokines suppress proliferation of hematopoietic progenitor cells (HPCs) in vitro; some of these have demonstrated inhibition of myelopoiesis in vivo. Because myelosuppressive chemokines synergize in vitro with other myelosuppressive chemokines, we sought to determine whether additional chemokines active in vitro were myelosuppressive in vivo and whether combinations of myelosuppressive chemokines synergized in vivo to dampen myelopoiesis. We also evaluated three chemokines in vivo for myeloprotection against Ara-C-induced decreases in HPCs. C3H/HeJ mice were used for analysis of in vivo influence of chemokines, with the end points being effects on absolute numbers and cycling status of HPCs. When used alone, CCL2, CCL3, CCL19, CCL20, CXCL4, CXCL5, CXCL8, CXCL9, and XCL1 caused dose-dependent significant decreases in absolute numbers and cycling status of HPCs in vivo. The following combinations of two chemokines resulted in in vivo myelosuppression at concentrations much lower than that induced by each chemokine alone: CCL3 plus either CXCL8 or CXCL4, CXCL8 plus CXCL4, CCL2 plus either CCL20 or CXCL9, CCL20 plus CXCL9, CXCL5 plus either XCL1 or CCL19, XCL1 plus CCL19, and CCL3 plus CCL19. Also, mice injected with CXCL8, CXCL4, or the chimeric CXCL8/CXCL4 protein CXCL8M1 manifested accelerated recovery of absolute numbers of HPCs in response to the toxic effects of Ara-C administration. A number of chemokines shown previously to manifest inhibitory effects in vitro for proliferation of HPCs are now demonstrated to also induce myelosuppression in vivo. Moreover, combinations of low dosages of two myelosuppressive chemokines when administered together demonstrate synergistic suppression in vivo. Additionally, chemokines, including a CXCL8M1 chimeric protein previously shown to manifest enhanced suppression of HPC proliferation in vitro and in vivo, accelerate HPC recovery after treatment of mice with Ara-C. These results may be of use for future clinical utility of chemokines in a myelosuppressive/myeloprotective setting.

High Tech for Milady's Makeup

NASA Technical Reports Server (NTRS)

1985-01-01

"Elizabeth," a computerized beauty analysis system marketed by Elizabeth Arden, is based upon an ARAC data base search of technologies measuring skin profiles. * "Elizabeth" is no longer commercially available.

Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.

PubMed

Qi, Na; Cai, Cuifang; Zhang, Wei; Niu, Yantao; Yang, Jingyu; Wang, Lihui; Tian, Bin; Liu, Xiaona; Lin, Xia; Zhang, Yu; Zhang, Yan; He, Haibing; Chen, Kang; Tang, Xing

2014-09-10

This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy.

PubMed

Liu, Jing; Zhao, Dujuan; He, Wenxiu; Zhang, Huiyuan; Li, Zhonghao; Luan, Yuxia

2017-02-01

The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH 2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared. The results of MTT assays on FR-positive K562 cells and FR-negative A549 cells demonstrated higher cytotoxicity of HA-Ara NAs than the native drug. Especially, the IC 50 values revealed that NAs/FA-BSA was 3 and 2-fold effective than non-targeted NAs after 24 and 48h treatment with K562 cells, respectively indicating FR-mediated enhanced anti-tumor efficacy. In vitro cellular uptake, larger accumulation of HA-Ara NAs were observed in comparative with the free FITC and the results further confirmed the selective uptake of NAs/FA-BSA in folate receptor enriched cancer cells. Above all, self-assembled HA-Ara NAs exhibited potential superiority for Ara-C delivery and FA-modified NAs would be an excellent candidate for targeting leukemia therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 60493 - Aviation Rulemaking Advisory Committee; Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Aviation Rulemaking Advisory Committee; Renewal AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of Renewal. SUMMARY... Aviation Rulemaking Advisory Committee (ARAC) for a 2-year period beginning September 17, 2010. The...

Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA-1 erythroid transcription factor.

PubMed

Foti, M; Omichinski, J G; Stahl, S; Maloney, D; West, J; Schweitzer, B I

1999-02-05

We investigate here the effects of the incorporation of the nucleoside analogs araC (1-beta-D-arabinofuranosylcytosine) and ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA-1 erythroid transcription factor. A 10-fold decrease in binding affinity was observed for the ganciclovir-substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1H-15N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir-modified DNA-protein complex when compared to the unmodified DNA-protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.

Murine and human leukemias.

PubMed

Burchenal, J H

1975-01-01

Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).

Türk Lise Öğrencilerinde Okul Terkinin Yordanması: Aracı ve Etkileşim Değişkenleri ile Bir Model Testi

PubMed Central

Özer, Arif; Gençtanirim, Dilek; Ergene, Tuncay

2011-01-01

Bu araştırmada ilk olarak, dürtüsel davranma ile okulu terk etme riski arasındaki ilişkiye disiplin cezası almanın, antisosyal davranışların ve sigara-alkol kullanımının aracılık edip etmediği incelenmiştir. İkinci olarak, öğretmen desteği ve antisosyal davranış etkileşiminin okulu terk etme riski üzerindeki etkisi test edilmiştir. Araştırma grubunu 2009-2010 yılında Ankara İlinde genel liselere devam eden 478 öğrenci oluşturmuştur. Sonuçlar okulu terk etme riskini aile ve arkadaş desteğinin azalttığını, dürtüsel davranmanın ise artırdığını göstermiştir. Ayrıca disiplin cezası, alkol-sigara kullanma ve antisosyal davranışlar okulu terk etme riskini artıran aracı değişkenlerdir. Antisosyal davranışlarla okulu terk etme arasındaki ilişki öğretmen desteğine bağlı olarak değişmektedir. Öğrencilerin cinsiyet ve başarıları ile okulu terk etme riskleri arasında anlamlı bir ilişki bulunmamaktadır. PMID:22003257

Comparison of the Antiviral Effects of 5-Methoxymethyl-deoxyuridine with 5-Iododeoxyuridine, Cytosine Arabinoside, and Adenine Arabinoside

PubMed Central

Babiuk, Lorne A.; Meldrum, Blair; Gupta, V. Sagar; Rouse, Barry T.

1975-01-01

The antiviral activity of 5-methoxymethyl-2′-deoxyuridine (MMUdR) was compared with that of 5-iodo-2′-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 μg/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 μg/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 μg/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%. PMID:1239978

The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats.

PubMed

Shiromoto, Takashi; Okabe, Naohiko; Lu, Feng; Maruyama-Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Yagita, Yoshiki; Kimura, Kazumi; Miyamoto, Osamu

2017-02-01

Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI). Ischemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C). Rehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI. After CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

General approach to, and perspectives on clinical research in, older patients with newly diagnosed acute myeloid leukemia.

PubMed

Estey, Elihu H

2006-04-01

Most patients aged>or=55 to 60 years who are treated for newly diagnosed acute myeloid leukemia (AML) receive a combination of an anthracycline plus cytarabine (ara-C). A principal thesis of this chapter is that such therapy is unsatisfactory for the great majority of such patients. In particular, the >or=15% risk of death in the month following the start of treatment is difficult to justify given median survivals of less than 1 year in the patients who do not die early. Thus, investigational therapy should be recommended for most, if not all, older patients. In patients for whom such therapy is not feasible, low-dose ara-C is a reasonable alternative except for patients with de novo disease and a normal karyotype, who might benefit more from an anthracycline+ara-C combination, and patients with either a poor performance status, abnormal organ function, or age>or=80, for whom supportive/palliative care only is recommended. Distinctions are made between investigational therapies likely associated with lower and higher risks of treatment-related mortality (TRM). The former are preferable initial treatment in patients aged 70 and above, or with abnormal cytogenetics. Three topics are discussed that are likely to be relevant to future clinical research in older patients: the possibility of delaying therapy to gain information about prognosis with initial induction therapy, the clinical value of responses less than conventional complete remission (CR), and the possibility of looking for larger differences between treatments in randomized clinical trials.

Learning Induces Sonic Hedgehog Signaling in the Amygdala which Promotes Neurogenesis and Long-Term Memory Formation

PubMed Central

Hung, Hui-Chi; Hsiao, Ya-Hsin

2015-01-01

Background: It is known that neurogenesis occurs throughout the life mostly in the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle. We investigated whether neurogenesis occurred in the amygdala and its function in fear memory formation. Methods: For detection of newborn neurons, mice were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU) 2h before receiving 15 tone–footshock pairings, and newborn neurons were analyzed 14 and 42 days after training. To determine the relationship between neurogenesis and memory formation, mice were given a proliferation inhibitor methylazoxymethanol (MAM) or a DNA synthesis inhibitor cytosine arabinoside (Ara-C). To test whether sonic hedgehog (Shh) signaling was required for neurogenesis, Shh-small hairpin–interfering RNA (shRNA) was inserted into a retroviral vector (Retro-Shh-shRNA). Results: The number of BrdU+/Neuronal nuclei (NeuN)+ cells was significantly higher in the conditioned mice, suggesting that association of tone with footshock induced neurogenesis. MAM and Ara-C markedly reduced neurogenesis and impaired fear memory formation. Shh, its receptor patched 1 (Ptc1), and transcription factor Gli1 protein levels increased at 1 day and returned to baseline at 7 days after fear conditioning. Retro-Shh-shRNA, which knocked down Shh specifically in the mitotic neurons, reduced the number of BrdU+/NeuN+ cells and decreased freezing responses. Conclusions: These results suggest that fear learning induces Shh signaling activation in the amygdala, which promotes neurogenesis and fear memory formation. PMID:25522410

76 FR 21936 - Aviation Rulemaking Advisory Committee-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... ARAC activity and solicits membership for the new Rulemaking Prioritization Working Group. FOR FURTHER... Rulemaking Prioritization Working Group will specifically address, in part, Recommendation 22: ``The... available * * *.'' The objective of the Rulemaking Prioritization Working Group is to provide advice and...

77 FR 69916 - Aviation Rulemaking Advisory Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

... Expectations 3. Recommendation Reports a. Rulemaking Prioritization Working Group (RPWG) Recommendation Report (ARAC) b. Avionics Systems Harmonization Working Group--Low Speed Alerting, Phase 2 Recommendation Report (TAE) 4. Status Reports From Active Working Groups a. Airman Testing Standards and Training...

77 FR 40699 - Aviation Rulemaking Advisory Committee Teleconference on Transport Airplane and Engine Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Aviation Rulemaking Advisory Committee Teleconference on Transport Airplane and Engine Issues AGENCY: Federal Aviation Administration... teleconference of the FAA's Aviation Rulemaking Advisory Committee (ARAC) to discuss transport airplane and...

78 FR 11728 - Aviation Rulemaking Advisory Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... Working Groups a. Airman Testing Standards and Training Working Group (ARAC) b. Flight Controls Harmonization Working Group (Transport Airplane and Engine Subcommittee [TAE]) c. Airworthiness Assurance Working Group (TAE) 3. New Tasks a. Engine Bird Ingestion Requirements--Revision of Section 33.76 b...

A novel biocatalytic approach to acetylation of 1-β-D-arabinofuranosylcytosine by Aspergillus oryzae whole cell in organic solvents.

PubMed

Li, Xiao-Feng; Zhu, Zhen; Zhao, Guang-Lei; Yu, Yi-Gang; Lai, Fu-Rao; Wu, Hui

2012-01-01

Biocatalytic acylation of 1-β-D-arabinofuranosylcytosine (ara-C) was developed using whole cell of Aspergillus oryzae as a novel catalyst. (13)C nuclear magnetic resonance (NMR) analysis indicated that the whole-cell biocatalyst had more specific activity toward the 3'-hydroxyl group than 5'-hydroxyl group among the available hydroxyl groups in sugar moiety of ara-C. Except for glucose and maltose, 11 carbon sources supplemented to basal media, including Spans, Tweens, olive oil and oleic acid, exhibited notable enhancement effects on both the cell growth and the acylation reactions. It was suggested that the carbon sources containing controlled-release oleic acid were the important substrates for the production of fungal cell-bound lipase with specific activity, partially due to a gradual induction effect of their released oleic acid on the cell-bound lipase production. Despite the low initial reaction rate and substrate conversion, the addition of 2.0 g/l Span 80 resulted in a higher 3'-regioselectivity of the cells than 81%. By using Tween 85 at its optimum concentration of 5.0 g/l, however, the highest initial rates (3.2 mmol/l h) and substrate conversion (76%) of the whole-cell catalyzed acylation of ara-C can be achieved. It was also found that the 3'-regioselectivity of the cells showed observable increase by extending the culture time. And the activity of cell-bound lipase drastically increased in the early stage of cell growth and then declined in the late culture stage, whatever the culture media used. Our results thus indicated that A. oryzae whole cell was a promising green tool for biosynthesis of nucleoside esters with potential bioactivities.

Small-Molecule Inhibitor of the Shigella flexneri Master Virulence Regulator VirF

PubMed Central

Koppolu, Veerendra; Osaka, Ichie; Skredenske, Jeff M.; Kettle, Bria; Hefty, P. Scott; Li, Jiaqin

2013-01-01

VirF is an AraC family transcriptional activator that is required for the expression of virulence genes associated with invasion and cell-to-cell spread by Shigella flexneri, including multiple components of the type three secretion system (T3SS) machinery and effectors. We tested a small-molecule compound, SE-1 (formerly designated OSSL_051168), which we had identified as an effective inhibitor of the AraC family proteins RhaS and RhaR, for its ability to inhibit VirF. Cell-based reporter gene assays with Escherichia coli and Shigella, as well as in vitro DNA binding assays with purified VirF, demonstrated that SE-1 inhibited DNA binding and transcription activation (likely by blocking DNA binding) by VirF. Analysis of mRNA levels using real-time quantitative reverse transcription-PCR (qRT-PCR) further demonstrated that SE-1 reduced the expression of the VirF-dependent virulence genes icsA, virB, icsB, and ipaB in Shigella. We also performed eukaryotic cell invasion assays and found that SE-1 reduced invasion by Shigella. The effect of SE-1 on invasion required preincubation of Shigella with SE-1, in agreement with the hypothesis that SE-1 inhibited the expression of VirF-activated genes required for the formation of the T3SS apparatus and invasion. We found that the same concentrations of SE-1 had no detectable effects on the growth or metabolism of the bacterial cells or the eukaryotic host cells, respectively, indicating that the inhibition of invasion was not due to general toxicity. Overall, SE-1 appears to inhibit transcription activation by VirF, exhibits selectivity toward AraC family proteins, and has the potential to be developed into a novel antibacterial agent. PMID:24002059

Synthesis of deoxyribonucleotidyl(3'5')arabinonucleosides

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

Gray, S.H.; Ainsworth, C.F.; Bell, C.L.

Two different synthetic routes using phosphotriester methodology have been utilized to prepare deoxyribonucleotidyl(3'-5)arabinonucleosides containing 9-..beta..-D-arabinofuranosyladenine (ara-A vidarabine) and 1-..beta..-D-arabinofuranosylcytosine (ara-C, cytarabine) at the 3'-terminus in amounts and purity (greater than 95%) suitable for NMR analysis.

Gas chromatography-mass spectrometry screening for phytochemical 4-desmethylsterols accumulated during development of Tunisian peanut kernels (Arachis hypogaea L.).

PubMed

Cherif, Aicha O; Trabelsi, Hajer; Ben Messaouda, Mhamed; Kâabi, Belhassen; Pellerin, Isabelle; Boukhchina, Sadok; Kallel, Habib; Pepe, Claude

2010-08-11

4-Desmethylsterols, the main component of the phytosterol fraction, have been analyzed during the development of Tunisian peanut kernels ( Arachis hypogaea L.), Trabelsia (AraT) and Chounfakhi (AraC), which are monocultivar species, and Arbi (AraA), which is a wild species, by gas chromatography-mass spectrometry. Immature wild peanut (AraA) showed the highest contents of beta-sitosterol (554.8 mg/100 g of oil), campesterol (228.6 mg/100 g of oil), and Delta(5)-avenasterol (39.0 mg/100 g of oil) followed by peanut cultivar AraC with beta-sitosterol, campesterol, and Delta(5)-avenasterol averages of 267.7, 92.1, and 28.6 mg/100 g of oil, respectively, and similarly for AraT 309.1, 108.4, and 27.4 mg/100 g of oil, respectively, were found. These results suggest that, in immature stages, phytosterol contents can be important regulator factors for the functional quality of peanut oil for the agro-industry chain from plant to nutraceuticals.

Deferasirox has strong anti-leukemia activity but may antagonize theanti-leukemia effect of doxorubicin.

PubMed

Chang, Yu-Chien; Lo, Wen-Jyi; Huang, Yu-Ting; Lin, Chaio-Lin; Feng, Chiu-Che; Lin, Hsin-Ting; Cheng, Hsu-Chen; Yeh, Su-Peng

2017-09-01

Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients. DFX induces cell cycle arrest at G1 phase and apoptosis and inhibits phosphorylation of ERK. We also showed that DFX antagonizes the anti-leukemic effect of DOX. On the contrary, combining DFX with Ara-C created a synergistic effect. Our study confirms the anti-leukemia activity of DFX and provides important information on how to select a partner drug for DFX for the treatment of AML in future clinical trials.

Inhibition of DNA replication in Saccharomyces cerevisiae by araCMP.

PubMed

McIntosh, E M; Kunz, B A; Haynes, R H

1986-01-01

Cytosine arabinoside (araC), a potent inhibitor of DNA replication in mammalian cells, was found to be completely ineffective in Saccharomyces cerevisiae. The 5' monophosphate derivative, araCMP, is toxic and effectively inhibits both nuclear and mitochondrial DNA synthesis in this organism. Although wild-type strains can be inhibited by araCMP, dTMP permeable (tup-) strains were found to be much more sensitive to the analogue. In vivo labelling experiments indicate that araC enters yeast cells; however, it is extensively catabolized by deamination and breakage of the glycosidic bond. In addition, the analogue is not efficiently phosphorylated in S. cerevisiae owing to an apparent lack of deoxynucleoside kinase activity. These results provide further evidence that deoxyribonucleotides can be synthesized only through de novo pathways in this organism. Finally, araCMP was found to be recombinagenic in S. cerevisiae which suggests, together with other previous studies, that, in general, inhibition of DNA synthesis in yeast promotes mitotic recombination events.

For the relief of Rosa Isela Figueroa Rincon, Miguel Angel Figueroa Rincon, Blanca Azucena Figueroa Rincon, and Nancy Araceli Figueroa Rincon.

THOMAS, 111th Congress

Rep. DeGette, Diana [D-CO-1

2009-02-12

House - 03/10/2009 Referred to the Subcommittee on Immigration, Citizenship, Refugees, Border Security, and International Law. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

77 FR 59243 - Aviation Rulemaking Advisory Committee Meeting on Transport Airplane and Engine Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... Committee Meeting on Transport Airplane and Engine Issues AGENCY: Federal Aviation Administration (FAA), DOT... Rulemaking Advisory Committee (ARAC) to discuss transport airplane and engine (TAE) issues. DATES: The... Prioritization Working Group Transport Canada Report Materials Flammability Working Group Report Avionics...

77 FR 10797 - Aviation Rulemaking Advisory Committee-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... Committee--New Task AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of withdrawal of task assignment for the Aviation Rulemaking Advisory Committee (ARAC). SUMMARY: The FAA has withdrawn a task... is to inform the public of the FAA's decision to withdraw this task. FOR FURTHER INFORMATION CONTACT...

78 FR 34423 - Aviation Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... private pilot certificate and the instrument rating. These documents are available for public review... Airman Testing Standards and Training (2) Draft PRIVATE PILOT--AIRPLANE Airman Certification Standards; (3) Draft Change Tracking Matrix referenced to FAA-S-8081-14B, Private Pilot Practical Test Standards...

78 FR 44619 - Aviation Rulemaking Advisory Committee (ARAC) Airman Testing Standards and Training Working Group...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... aviation accidents by incorporating task-specific risk management considerations into each Area of... the Fundamentals of Instructing (FOI) concepts listed in 14 CFR part 61. Consistent with its desire... the instrument rating ACS, its construction reflects fundamental differences between the family of...

75 FR 27857 - Aviation Rulemaking Advisory Committee; Transport Airplane and Engine Issue Area-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... (autopilot) and performance and handling qualities in icing conditions to improve transport airplane... the existing Avionics Systems Harmonization Working Group. The Task ARAC is initially tasked with... working group will be expected to provide a report that addresses the following low speed alerting...

78 FR 15110 - Aviation Rulemaking Advisory Committee; Engine Bird Ingestion Requirements-New Task

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

...: During the bird-ingestion rulemaking database (BRDB) working group`s reevaluation of the current engine... engine core ingestion. If the BRDB working group`s reevaluation determines that such requirements are... Task ARAC accepted the task and will establish the Engine Harmonization Working Group (EHWG), under the...

Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine. Second case report.

PubMed

Islam, Anwarul

2017-09-01

We show for the second time that intramarrow injection/administration of chemotherapeutic agents such as cytarabine (Ara-C) can be used safely and effectively and is associated with no toxicity, promising antileukemic activity and possible improved survival.

The RclR Protein Is a Reactive Chlorine-specific Transcription Factor in Escherichia coli *

PubMed Central

Parker, Benjamin W.; Schwessinger, Emily A.; Jakob, Ursula; Gray, Michael J.

2013-01-01

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance. PMID:24078635

The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli.

PubMed

Parker, Benjamin W; Schwessinger, Emily A; Jakob, Ursula; Gray, Michael J

2013-11-08

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.

78 FR 72141 - Aviation Rulemaking Advisory Committee; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

... Standard Time. Arrange oral presentations by December 12, 2013. ADDRESSES: The meeting will take place at... Act (5 U.S.C. App. 2), we are giving notice of a meeting of the ARAC taking place on December 19, 2013... includes: 1. Recommendation Report a. Flight Controls Harmonization Working Group (Transport Airplane and...

The aflatoxin B1 -fumonisin B1 toxicity in BRL-3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism.

PubMed

Mary, Verónica S; Arias, Silvina L; Otaiza, Santiago N; Velez, Pilar A; Rubinstein, Héctor R; Theumer, Martín G

2017-06-01

Human oral exposure to aflatoxin B 1 (AFB 1 ) and fumonisin B 1 (FB 1 ) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB 1 -FB 1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB 1 -FB 1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB 1 metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors. Flow cytometry of stained BRL-3A hepatocytes was used to study the cell cycle (propidium iodide), ROS intracellular production (DCFH-DA, HE, DAF-2 DA), and phospholipase A activity (staining with bis-BODIPY FL C11-PC). The CYP1A activity was assessed by the 7-ethoxyresorufin-O-deethylase (EROD) assay. Despite a 48-h exposure to FB 1 (30 μM) not being genotoxic, the AFB 1 (20 μM)-induced micronucleus frequency was overcome by the AFB 1 -FB 1 mixture (MIX), presumably showing toxin interaction. The mycotoxins blocked G1/S-phase, but only MIX caused cell death. Overall, the oxidative stress led these alterations as the pretreatment with N-acetyl-l-cysteine reduced such toxic effects. While AFB 1 had a major input to the MIX pro-oxidant activity, with CYP and ArAc metabolism being ROS contributors, these pathways were not involved in the FB 1 -elicited weak oxidative stress. The MIX-induced micronucleus frequency in N-acetyl-l-cysteine pretreated cells was greater than that caused by AFB 1 without antioxidants, suggesting enhanced AFB 1 direct genotoxicity probably owing to the higher CYP activity and ArAc metabolism found in MIX. The metabolic pathways modulation by AFB 1 -FB 1 mixtures could raise its hepatocarcinogenic properties. © 2017 Wiley Periodicals, Inc.

Development of a new fluorescent reporter:operator system: location of AraC regulated genes in Escherichia coli K-12.

PubMed

Sellars, Laura E; Bryant, Jack A; Sánchez-Romero, María-Antonia; Sánchez-Morán, Eugenio; Busby, Stephen J W; Lee, David J

2017-08-03

In bacteria, many transcription activator and repressor proteins regulate multiple transcription units that are often distally distributed on the bacterial genome. To investigate the subcellular location of DNA bound proteins in the folded bacterial nucleoid, fluorescent reporters have been developed which can be targeted to specific DNA operator sites. Such Fluorescent Reporter-Operator System (FROS) probes consist of a fluorescent protein fused to a DNA binding protein, which binds to an array of DNA operator sites located within the genome. Here we have developed a new FROS probe using the Escherichia coli MalI transcription factor, fused to mCherry fluorescent protein. We have used this in combination with a LacI repressor::GFP protein based FROS probe to assess the cellular location of commonly regulated transcription units that are distal on the Escherichia coli genome. We developed a new DNA binding fluorescent reporter, consisting of the Escherichia coli MalI protein fused to the mCherry fluorescent protein. This was used in combination with a Lac repressor:green fluorescent protein fusion to examine the spatial positioning and possible co-localisation of target genes, regulated by the Escherichia coli AraC protein. We report that induction of gene expression with arabinose does not result in co-localisation of AraC-regulated transcription units. However, measurable repositioning was observed when gene expression was induced at the AraC-regulated promoter controlling expression of the araFGH genes, located close to the DNA replication terminus on the chromosome. Moreover, in dividing cells, arabinose-induced expression at the araFGH locus enhanced chromosome segregation after replication. Regions of the chromosome regulated by AraC do not colocalise, but transcription events can induce movement of chromosome loci in bacteria and our observations suggest a role for gene expression in chromosome segregation.

Induction of S phase cell arrest and caspase activation by polysaccharide peptide isolated from Coriolus versicolor enhanced the cell cycle dependent activity and apoptotic cell death of doxorubicin and etoposide, but not cytarabine in HL-60 cells.

PubMed

Hui, Kenrie Pui-Yan; Sit, Wai-Hung; Wan, Jennifer Man-Fan

2005-07-01

Activation of the cell death program (apoptosis) is a strategy for the treatment of human cancer, and unfortunately a large number of drugs identified as cell cycle-specific agents for killing cancer cells are also toxic to normal cells. The present study demonstrates that the polysaccharide peptide (PSP) extracted from the Chinese medicinal mushroom, Coriolus versicolor, used in combination therapy in China, has the ability to lower the cytotoxicity of certain anti-leukemic drugs via their interaction with cell cycle-dependent and apoptotic pathways. Flow cytometry analysis demonstrated that pre-treatment of PSP (25-100 microg/ml) dose-dependently enhanced the cell cycle perturbation and apoptotic activity of doxorubicin (Doxo) and etoposide (VP-16), but not cytarabine (Ara-C) in human promyelocytic leukemia HL-60 cells. The antagonistic result from combined treatment with Ara-C and PSP may be caused by the removal of HL-60 cells in the G1-S boundary by PSP before exposure to Ara-C. A negative correlation between the increase in apoptotic cell population (pre-G1 peak) with the S-phase cell population expression (R2=0.998), the expression of cyclin E expression (R2=0.872) and caspase 3 activity (R2=0.997) suggests that PSP enhanced the apoptotic machinery of Doxo and VP-16 in a cell cycle-dependent manner and is mediated, at least in part, by the PSP-mediated modulation of the regulatory checkpoint cyclin E and caspase 3. This study is the first to describe the cell cycle mechanistic action of PSP and its interaction with other anticancer agents. Our data support the potential development of PSP as an adjuvant for leukemia treatment, but also imply the importance of understanding its interaction with individual anticancer agents.

MarA, SoxS and Rob of Escherichia coli - Global regulators of multidrug resistance, virulence and stress response.

PubMed

Duval, Valérie; Lister, Ida M

2013-01-01

Bacteria have a great capacity for adjusting their metabolism in response to environmental changes by linking extracellular stimuli to the regulation of genes by transcription factors. By working in a co-operative manner, transcription factors provide a rapid response to external threats, allowing the bacteria to survive. This review will focus on transcription factors MarA, SoxS and Rob in Escherichia coli , three members of the AraC family of proteins. These homologous proteins exemplify the ability to respond to multiple threats such as oxidative stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides. MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more than 40 regulatory target genes. As their regulons overlap, a finely tuned adaptive response allows E. coli to survive in the presence of different assaults in a co-ordinated manner. These regulators are well conserved amongst Enterobacteriaceae and due to their broad involvement in bacterial adaptation in the host, have recently been explored as targets to develop new anti-virulence agents. The regulators are also being examined for their roles in novel technologies such as biofuel production.

Development of a Cavum Septi Pellucidi after Ommaya Reservoir Placement: A Cause of Shunt Malfunction

DTIC Science & Technology

2005-09-01

pellucidi (Figure 1). After the first injection of intrathecal cytarabine (Ara-C) via the Ommaya reservoir the patient experienced a generalized tonic...methotrexate and cytarabine . Child’s Nerv Syst 1990; 6: 231-235. 3. Lishner M, Perrin RG, Feld R, Messner HA, Tuffnell PG, Elhakim T, Matlow A, Curtis JE

Cold Regions Test of Indirect Fire Weapons Ammunition

DTIC Science & Technology

1983-03-08

COLD REGIONS TEST OF INDIRECT FIRE WEAPONS AMMUNITION Paragraph 1 . SCOPE. 1 2. FACILITIES AND INSTRUMENTATION .......... 3. PREPARATION FOR TEST...A- 1 B. Data Collection Sheets ..... .............. B- 1 C. References ..... .................... ... C- 1 D. Cold-Dry...Uniform .D...... .. ... .. ... 0- 1 1 . SCOPE. The procedures outlined in this TOP are designed to determine the c-h-arac-teristics of indirect artillery

76 FR 11844 - Aviation Rulemaking Advisory Committee; Transport Airplane and Engine Issue Area-Phase 2 of Low...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... new designs, the working group should state the rationale and not repeat the information previously... design changes, or would an operational rule be sufficient? In responding, the working group should... the public that the ARAC working group has completed activity for Phase 1 of the task and will begin...

Nonidentity of Some Simian Virus 40-induced Enzymes with Tumor Antigen

PubMed Central

Kit, Saul; Melnick, Joseph L.; Anken, Milton; Dubbs, Del Rose; de Torres, R. A.; Kitahara, Tsunehiro

1967-01-01

The complement-fixing tumor (T) antigen induced by simian virus 40 (SV40) has been prepared from SV40-infected cell cultures, from infected cell cultures treated at the time of infection with 1-β-d-arabinofuranosylcytosine (ara-C), and from SV40-transformed cells. Upon partial purification, the T antigen exhibited the following properties: it was tightly adsorbed by calcium phosphate gel, it was precipitated by acetic acid at pH 5 or by ammonium sulfate at about 20 to 32% saturation, and it had a molecular weight greater than 250,000, as estimated by Sephadex G-200 gel chromatography. In contrast, deoxycytidylate (dCMP) deaminase, thymidylate (dTMP) kinase, and thymidine (dT) kinase were less strongly bound to calcium phosphate and were not precipitated at pH 5; these enzymes also had much lower molecular weights than the T antigen, as did dihydrofolic (FH2) reductase. Furthermore, higher ammonium sulfate concentrations were required to precipitate dCMP deaminase, dTMP kinase, and FH2 reductase activities than to precipitate the T antigen. Another difference was that the T antigen was not stabilized, but dCMP deaminase, dTMP kinase, and dT kinase, were stabilized, respectively, by dCTP, dTMP, and dT or dTTP. Deoxyribonucleic acid (DNA) polymerase activity resembled the T antigen in adsorption to calcium phosphate, in precipitation by ammonium sulfate or at pH 5, and in the rate of inactivation when incubated at 38 C. However, the polymerase activity could be partly separated from the T antigen by Sephadex G-200 gel chromatography. The cell fraction containing partially purified T antigen also contained a soluble complement-fixing antigen (presumably a subunit of the viral capsid) which reacted with hyperimmune monkey sera. The latter antigen was present in very low titers or absent from cell extracts prepared from SV40-infected monkey kidney cell cultures which had been treated with ara-C at the time of infection, or from SV40-transformed mouse kidney (mKS) or hamster tumor (H-50) cells. The T antigen, however, was present in usual amounts in SV40-transformed cells or ara-C treated, infected cells. PMID:4316227

Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature.

PubMed

McIlwain, Laura; Sokol, Lubomir; Moscinski, Lynn C; Saba, Hussain I

2003-04-01

We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

Hydrocarbon productivities in different Botryococcus strains: comparative methods in product quantification.

PubMed

Eroglu, Ela; Okada, Shigeru; Melis, Anastasios

2011-08-01

Six different strains of the green microalgae Botryococcus belonging to the A-race or B-race, accumulating alkadiene or botryococcene hydrocarbons, respectively, were compared for biomass and hydrocarbon productivities. Biomass productivity was assessed gravimetrically upon strain growth in the laboratory under defined conditions. Hydrocarbon productivities were measured by three different and independent experimental approaches, including density equilibrium of the intact cells and micro-colonies, spectrophotometric analysis of hydrocarbon extracts, and gravimetric quantitation of eluted hydrocarbons. All three hydrocarbon-quantitation methods yielded similar results for each of the strains examined. The B-race microalgae Botryococcus braunii var. Showa and Kawaguchi-1 constitutively accumulated botryococcene hydrocarbons equivalent to 30% and 20%, respectively, of their overall biomass. The A-race microalgae Botryococcus braunii, varieties Yamanaka, UTEX 2441 and UTEX LB572 constitutively accumulated alkadiene hydrocarbons ranging from 14% to 13% and 10% of their overall biomass, respectively. Botryococcus sudeticus (UTEX 2629), a morphologically different green microalga, had the lowest hydrocarbon accumulation, equal to about 3% of its overall biomass. Results validate the density equilibrium and spectrophotometric analysis methods in the quantitation of botryococcene-type hydrocarbons. These analytical advances will serve in the screening and selection of B. braunii and of other microalgae in efforts to identify those having a high hydrocarbon content for use in commercial applications.

Stimulation of Breast Tumor Cell Proliferative Recovery by the Peptide Hormone Erythropoietin

DTIC Science & Technology

2006-08-01

against apoptosis induced by chemotherapy, F-MEL leukemic cells treated with or without EPO were exposed to either cytarabine (Ara-C) or daunorubicin...F-MEL erythroleukemia cells is suppressed by treatment with cytarabine ( Ara C) or daunorubicin. Cells were incubated in the absence or presence...antiproliferative and/or cytotoxic effects of Adriamycin,Taxol, and tamoxifen in breast tumor cells (or of cytarabine and daunorubicin in F-MEL cells). EPO failed to

Targeted Ablation of CML Stem Cells

DTIC Science & Technology

2007-01-01

centuries .12 More recently, PTL has been found to have several other properties, including antitumor activity, inhibition of DNA synthesis, and...as a chemopreventive agent in a UVB-induced skin cancer animal model. 21 PTL is a potent inhibitor of NF-B activation and has been shown to directly...diluted in phosphate buffer saline (PBS). Ara-C was obtained from Sigma ( St Louis, MO). Total cell numbers were determined before and after culture for

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

PubMed

Ueda, T; Kawai, Y; Sugiyama, T; Takeuchi, N; Yoshida, A; Iwasaki, H; Wano, Y; Tsutani, H; Kamada, N; Nakamura, T

1993-12-01

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

DOC/WSNSO (Department of Commerce/Weather Service Nuclear Support Office) operational support to Federal Radiological Monitoring and Assessment Center

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

Mueller, P.

1989-01-01

The National Weather Service (NWS) is an agency of the Department of Commerce. The NWS has hundreds of weather offices throughout the United States. The Weather Service Nuclear Support Office (WSNSO) is a highly specialized unit of NWS that provides direct support to the U.S. Department of Energy's (DOE's) underground nuclear testing program. The WSNSO has been associated with the DOE for >33 yr. As a result of the unique relationship with the DOE, all WSNSO emergency response meteorologists and meteorological technicians are allowed access to classified material. Meteorological phenomena play a significant role during a Federal Radiological Monitoring andmore » Assessment Center (FRMAC) event, and WSNSO meteorologists provide direct support to ARAC. The marriage of state-of-the-art computer systems together with proven technology provides the on-scene WSNSO meteorologist with essentially a portable fully equipped, fully functional, advanced NWS weather station. The WSNSO's emergency response personnel and hardware are at the ready and can be mobilized within 2 h. WSNSO can provide on-scene weather forecasts and critical weather data collection whenever and wherever necessary.« less

Molecular mechanism for sphingosine-induced Pseudomonas ceramidase expression through the transcriptional regulator SphR

PubMed Central

Okino, Nozomu; Ito, Makoto

2016-01-01

Pseudomonas aeruginosa, an opportunistic, but serious multidrug-resistant pathogen, secretes a ceramidase capable of cleaving the N-acyl linkage of ceramide to generate fatty acids and sphingosine. We previously reported that the secretion of P. aeruginosa ceramidase was induced by host-derived sphingolipids, through which phospholipase C-induced hemolysis was significantly enhanced. We herein investigated the gene(s) regulating sphingolipid-induced ceramidase expression and identified SphR, which encodes a putative AraC family transcriptional regulator. Disruption of the sphR gene in P. aeruginosa markedly decreased the sphingomyelin-induced secretion of ceramidase, reduced hemolytic activity, and resulted in the loss of sphingomyelin-induced ceramidase expression. A microarray analysis confirmed that sphingomyelin significantly induced ceramidase expression in P. aeruginosa. Furthermore, an electrophoretic mobility shift assay revealed that SphR specifically bound free sphingoid bases such as sphingosine, dihydrosphingosine, and phytosphingosine, but not sphingomyelin or ceramide. A β-galactosidase-assisted promoter assay showed that sphingosine activated ceramidase expression through SphR at a concentration of 100 nM. Collectively, these results demonstrated that sphingosine induces the secretion of ceramidase by promoting the mRNA expression of ceramidase through SphR, thereby enhancing hemolytic phospholipase C-induced cytotoxicity. These results facilitate understanding of the physiological role of bacterial ceramidase in host cells. PMID:27941831

Acute leukemia occurring after radiotherapy and chemotherapy with a nitrosourea, PCNU.

PubMed

Shepard, K V; Larson, R; Le Beau, M M; Leichman, L; Levin, B

1988-06-01

Secondary acute leukemias can occur in patients who have been treated with chemotherapy. Several reports have shown that treatment with nitrosoureas can result in secondary leukemia, but this is the first report implicating the investigational drug PCNU as a cause. This case is unique because of the cytogenetic findings, the short latency period between the chemotherapy and the diagnosis of leukemia, and the successful treatment of the leukemia with high-dose cytarabine (ara-C).

Polyphosphate Affects on Breast Cancer Cell Survival

DTIC Science & Technology

2007-04-01

not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 01-04-2007 2...and verify the strains that were developed. Strains without UvrA are extremely sensitive to UV light so the screen easily displays the strains with...2007) W81XWH-04-1-0379 P.I. Christine Haakenson pPPK 6609 bp Selectable Marker Promoter BAD prom MCS M13 intergenic region pBR322 ORI rrnB araC

Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan.

PubMed

Konuma, Takaaki; Takahashi, Satoshi; Uchida, Naoyuki; Kuwatsuka, Yachiyo; Yamasaki, Satoshi; Aoki, Jun; Onishi, Yasushi; Aotsuka, Nobuyuki; Ohashi, Kazuteru; Mori, Takehiko; Masuko, Masayoshi; Nakamae, Hirohisa; Miyamura, Kouichi; Kato, Koji; Atsuta, Yoshiko; Kato, Seiko; Asano, Shigetaka; Takami, Akiyoshi; Miyazaki, Yasushi

2015-09-01

Granulocyte colony-stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF-combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) ≥ 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI ≥ 8 Gy + Ara-C + CY (n = 119), TBI ≥ 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI ≥ 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF-combined conditioning regimen provides better engraftment and survival results in CBT for adults with MDS and sAML. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

[Prediction of School Dropout among Turkish High School Students: A Model Testing with Moderator and Mediator Variables.

PubMed

Ozer, Arif; Gençtanirim, Dilek; Ergene, Tuncay

2011-01-01

Bu araştırmada ilk olarak, dürtüsel davranma ile okulu terk etme riski arasındaki ilişkiye disiplin cezası almanın, antisosyal davranışların ve sigara-alkol kullanımının aracılık edip etmediği incelenmiştir. İkinci olarak, öğretmen desteği ve antisosyal davranış etkileşiminin okulu terk etme riski üzerindeki etkisi test edilmiştir. Araştırma grubunu 2009-2010 yılında Ankara İlinde genel liselere devam eden 478 öğrenci oluşturmuştur. Sonuçlar okulu terk etme riskini aile ve arkadaş desteğinin azalttığını, dürtüsel davranmanın ise artırdığını göstermiştir. Ayrıca disiplin cezası, alkol-sigara kullanma ve antisosyal davranışlar okulu terk etme riskini artıran aracı değişkenlerdir. Antisosyal davranışlarla okulu terk etme arasındaki ilişki öğretmen desteğine bağlı olarak değişmektedir. Öğrencilerin cinsiyet ve başarıları ile okulu terk etme riskleri arasında anlamlı bir ilişki bulunmamaktadır.

Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes.

PubMed

Lepelley, P; Poulain, S; Grardel, N; Preudhomme, C; Cosson, A; Fenaux, P

1998-05-01

The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.

Quarterly literature review of the remote sensing of natural resources

NASA Technical Reports Server (NTRS)

Fears, C. B. (Editor); Inglis, M. H. (Editor)

1977-01-01

The Technology Application Center reviewed abstracted literature sources, and selected document data and data gathering techniques which were performed or obtained remotely from space, aircraft or groundbased stations. All of the documentation was related to remote sensing sensors or the remote sensing of the natural resources. Sensors were primarily those operating within the 10 to the minus 8 power to 1 meter wavelength band. Included are NASA Tech Briefs, ARAC Industrial Applications Reports, U.S. Navy Technical Reports, U.S. Patent reports, and other technical articles and reports.

The role of nanoparticles in the albumin-cytarabine and albumin-methotrexate interactions.

PubMed

Pentak, Danuta; Maciążek-Jurczyk, Małgorzata; Zawada, Zygmunt H

2017-04-01

Understanding the interactions which occur between nanomaterials and biomolecules is one of the most important issues in nanotechnology. Determining the properties of nanoparticles obtained through the use of novel methods and defining the scope of their application as drug carriers has important practical significance. Nanoparticles containing methotrexate and cytarabine obtained by a modified reverse-phase evaporation method (mREV) were characterized through the use of the UV/Vis and NMR methods. Obtained results confirmed high degree of analysed drugs encapsulation. The encapsulation efficiencies of cytarabine (AraC) and methotrexate (MTX) in L DPPC/AraC/MTX were found to be 86.30% (AraC) and 86.00% (MTX). The increased permeability of the phospholipid membranes, resulting from physico-chemical properties and the location of the drug, as well as from the physico-chemical properties of the phospholipids themselves, has been confirmed by increase in the length of the T1 relaxation time of protons in the N + (CH 3 ) 3 group. The study of analysed drugs release process from the liposomes has been made for bovine serum albumin, both in the absence (dBSA) and in the presence of fatty acid (BSA). Moreover two types of kinetic models (Bhaskar equation and Rigter-Peppas equation) have been used. Based on the study it has been concluded that mathematical modelling of drug release can be very helpful in speeding up product development and in better understanding the mechanisms controlling drug release from advanced delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary-adrenal axis.

PubMed

Colagiovanni, Dorothy B; Drolet, Daniel W; Dihel, Larry; Meyer, Dennis J; Hart, Karen; Wolf, Julie

2006-01-01

4'-Thio-beta-D-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression, reversible transaminase elevations, and flu-like symptoms are common side effects associated with human use of gemcitabine and ara-C. Fatigue is also associated with the use of gemcitabine and OSI-7836 in humans. To better understand the toxicity of OSI-7836, subchronic studies were conducted in dogs. OSI-7836 was administered on days 1 and 8 or on days 1, 2, and 3 of a 21-day dose regimen. These schedules attempted to match clinical trial dosing regimens. Routine toxicity study end points demonstrated that OSI-7836 was primarily cytotoxic to the gastrointestinal tract, bone marrow, and testes; the myelotoxicity was mild and reversible. Plasma pharmacokinetics were dose-linear with an elimination half-life of 2.2 h. Follow-up single dose experiments in dogs assessed drug effects on lymphocyte subpopulations and on adrenal and thyroid function. Populations of T and B cells were equally reduced following OSI-7836 administration. There were no adverse effects on thyroid function, but there were marked reductions in circulating cortisol and adrenocorticotropic hormone concentrations suggesting a centrally mediated impairment of the hypothalamic-pituitary-adrenal axis. These findings show a toxicological profile with OSI-7836 similar to other nucleoside analogues and suggest that the beagle is a model for studying one possible cause of OSI-7836-related fatigue, impaired function of the hypothalamic-pituitary-adrenal axis.

Highly efficient generation of glutamatergic/cholinergic NT2-derived postmitotic human neurons by short-term treatment with the nucleoside analogue cytosine β-D-arabinofuranoside.

PubMed

González-Burguera, Imanol; Ricobaraza, Ana; Aretxabala, Xabier; Barrondo, Sergio; García del Caño, Gontzal; López de Jesús, Maider; Sallés, Joan

2016-03-01

The human NTERA2/D1 (NT2) cells generate postmitotic neurons (NT2N cells) upon retinoic acid (RA) treatment and are functionally integrated in the host tissue following grafting into the rodent and human brain, thus representing a promising source for neuronal replacement therapy. Yet the major limitations of this model are the lengthy differentiation procedure and its low efficiency, although recent studies suggest that the differentiation process can be shortened to less than 1 week using nucleoside analogues. To explore whether short-term exposure of NT2 cells to the nucleoside analogue cytosine β-d-arabinofuranoside (AraC) could be a suitable method to efficiently generate mature neurons, we conducted a neurochemical and morphometric characterization of AraC-differentiated NT2N (AraC/NT2N) neurons and improved the differentiation efficiency by modifying the cell culture schedule. Moreover, we analyzed the neurotransmitter phenotypes of AraC/NT2N neurons. Cultures obtained by treatment with AraC were highly enriched in postmitotic neurons and essentially composed of dual glutamatergic/cholinergic neurons, which contrasts with the preferential GABAergic phenotype that we found after RA differentiation. Taken together, our results further reinforce the notion NT2 cells are a versatile source of neuronal phenotypes and provide a new encouraging platform for studying mechanisms of neuronal differentiation and for exploring neuronal replacement strategies. Copyright © 2016 University of Texas at Austin Dell Medical School. Published by Elsevier B.V. All rights reserved.

Evaluation of γ-Induced Apoptosis in Human Peripheral Blood Lymphocytes

NASA Astrophysics Data System (ADS)

Baranova, Elena; Boreyko, Alla; Ravnachka, Ivanka; Saveleva, Maria

2010-01-01

Several experiments have been performed to study regularities in the induction of apoptotic cells in human lymphocytes by 60Co γ-rays at different times after irradiation. Apoptosis induction by 60Co γ-rays in human lymphocytes in different cell cycle phases (G0, S, G1, and G2) has been studied. The maximal apoptosis output in lymphocyte cells was observed in the S phase. Modifying effect of replicative and reparative DNA synthesis inhibitors—1- β -D-arabinofuranosylcytosine (Ara-C) and hydroxyurea (Hu)—on the kinetics of 60Co γ-rays induced apoptosis in human lymphocytes has been studied.

Functional Domains of the TOL Plasmid Transcription Factor XylS

PubMed Central

Kaldalu, Niilo; Toots, Urve; de Lorenzo, Victor; Ustav, Mart

2000-01-01

The alkylbenzoate degradation genes of Pseudomonas putida TOL plasmid are positively regulated by XylS, an AraC family protein, in a benzoate-dependent manner. In this study, we used deletion mutants and hybrid proteins to identify which parts of XylS are responsible for the DNA binding, transcriptional activation, and benzoate inducibility. We found that a 112-residue C-terminal fragment of XylS binds specifically to the Pm operator in vitro, protects this sequence from DNase I digestion identically to the wild-type (wt) protein, and activates the Pm promoter in vivo. When overexpressed, that C-terminal fragment could activate transcription as efficiently as wt XylS. All the truncations, which incorporated these 112 C-terminal residues, were able to activate transcription at least to some extent when overproduced. Intactness of the 210-residue N-terminal portion was found to be necessary for benzoate responsiveness of XylS. Deletions in the N-terminal and central regions seriously reduced the activity of XylS and caused the loss of effector control, whereas insertions into the putative interdomain region did not change the basic features of the XylS protein. Our results confirm that XylS consists of two parts which probably interact with each other. The C-terminal domain carries DNA-binding and transcriptional activation abilities, while the N-terminal region carries effector-binding and regulatory functions. PMID:10648539

[Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

PubMed

Wang, Fan; Yuan, Hai-Long; Duan, Xian-Lin; Wang, Lei; Cao, Hai-Zhou; Xu, Jian-Li; Qu, Jian-Hua

2014-08-01

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

[Efficacy of granisetron for preventing chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia treated with a combination of anthracycline and cytarabine].

PubMed

Goto, Takashi; Tanimoto, Kazuki; Ishibashi, Makoto; Okamura, Seiichi

2012-08-01

In Japan, the combination of anthracycline and cytarabine(Ara-C)is a standard therapy for acute myelogenous leukemia(AML). Chemotherapy-induced nausea and vomiting(CINV)are frequently reported as side effects related to the administration of these regimens. In our hospital, patients received prophylactic granisetron at a dose of 3 mg daily during chemotherapy. However, granisetron is known to induce constipation as a side effect. The present study evaluated the efficacy of a single dose of granisetron administered throughout the entire period of chemotherapy in AML patients receiving anthracycline and Ara-C combination therapy, and also examined the incidence of constipation during chemotherapy. From July 2008 to December 2010, all patients with AML treated using anthracycline and Ara-C combination therapy were registered in the study. This retrospective study investigated the patients' background and the incidence of CINV and constipation from the patients' records. The efficacy of granisetron was measured on each day using the complete regression(no vomiting and no rescue medication; CR)rate. A total of 45 patients were included in the study(27 male; 18 female), and received a total 68 courses(56 of induction therapy; 12 of consolidation therapy)of the regimens. The CR rate and the incidence of constipation on the final day of chemotherapy were 61. 8% and 63. 2%, respectively. As the duration of chemotherapy increased, the CR rate tended to decrease, whereas the incidence of constipation tended to increase. The CR rate in this study was 61. 8%, thus indicating that there is still room for improvement. The combination of dexamethasone and a neurokinin-1 receptor antagonist, or the changeover from granisetron to palonosetron could therefore increase the CR rate.

High Dose Cytosine Arabinoside in the consolidation of adult acute myeloid leukemia.

PubMed

Rahman, M H; Khan, M A; Islam, M S; Afrose, S; Ara, T

2012-04-01

This interventional study was done to evaluate the duration of remission with High Dose Cytosine Arabinoside (Ara-C) as post-remission chemotherapy in the consolidation of adult acute myeloid leukemia. A total of 32 patients were included in this study. Among them, 19 were male and 13 were female and the age of the patients ranges from 15-60 years. We use High Dose Cytosine Arabinoside 1.5-2.5 g/m2 i.v, 12 hourly, over 2-3 hours on day 1, 3 and 5 in a 28 days cycle. This study was done during the period of April 2007 to March 2009 in the department of hematology, Dhaka Medical College & Hospital. History, clinical features and laboratory investigations were included. Among 32 patients, 5 patients (15.6%) received one cycle, 20 patients (62.5%) received two cycles and 7 patients (21.9%) received three cycles. The mean ± SD duration of remission (disease free survival) was 5.20 ± 3.83 months who received one cycle, 9.55 ± 3.30 months and 10.71 ± 1.70 months who received two cycles and three cycles respectively. The adverse effects of the therapy were neutropenia and neutropenic fever, purpuric rash, gum bleeding, mucositis and peripheral neuropathy. The supportive materials needed were antibiotics (both prophylactic and treatment) 86.13%, blood and blood products 51.7% and G-CSF 14.9% patients of all cycles. High Dose Ara-C (HiDAC) is a safe and cost effective consolidation treatment for AML patients in complete remission. This therapy merits multi-center control study to define its efficacy and cost-effectiveness in contrast to our socio-economic condition.

The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models.

PubMed

Sredni, B; Xu, R H; Albeck, M; Gafter, U; Gal, R; Shani, A; Tichler, T; Shapira, J; Bruderman, I; Catane, R; Kaufman, B; Whisnant, J K; Mettinger, K L; Kalechman, Y

1996-01-03

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-I studies, preliminary results from phase-II clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1 RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1 alpha. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Establishment of a long-term spiral ganglion neuron culture with reduced glial cell number: Effects of AraC on cell composition and neurons.

PubMed

Schwieger, Jana; Esser, Karl-Heinz; Lenarz, Thomas; Scheper, Verena

2016-08-01

Sensorineural deafness is mainly caused by damage to hair cells and degeneration of the spiral ganglion neurons (SGN). Cochlear implants can functionally replace lost hair cells and stimulate the SGN electrically. The benefit from cochlear implantation depends on the number and excitability of these neurons. To identify potential therapies for SGN protection, in vitro tests are carried out on spiral ganglion cells (SGC). A glial cell-reduced and neuron-enhanced culture of neonatal rat SGC under mitotic inhibition (cytarabine (AraC)) for up to seven days is presented. Serum containing and neurotrophin-enriched cultures with and without AraC-addition were analyzed after 4 and 7 days. The total number of cells was significantly reduced, while the proportion of neurons was greatly increased by AraC-treatment. Cell type-specific labeling demonstrated that nearly all fibroblasts and most of the glial cells were removed. Neither the neuronal survival, nor the neurite outgrowth or soma diameter were negatively affected. Additionally neurites remain partly free of surrounding non-neuronal cells. Recent culture conditions allow only for short-term cultivation of neonatal SGC and lack information on the influence of non-neuronal cells on SGN and of direct contact of neurites with test-materials. AraC-addition reduces the number of non-neuronal cells and increases the ratio of SGN in culture, without negative impact on neuronal viability. This treatment allows longer-term cultivation of SGC and provides deeper insight into SGN-glial cell interaction and the attachment of neurites on test-material surfaces. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type.

PubMed

Michot, Jean-Marie; Mazeron, Renaud; Danu, Alina; Lazarovici, Julien; Ghez, David; Antosikova, Anna; Willekens, Christophe; Chamseddine, Ali N; Minard, Veronique; Dartigues, Peggy; Bosq, Jacques; Carde, Patrice; Koscielny, Serge; De Botton, Stéphane; Ferme, Christophe; Girinsky, Theodore; Ribrag, Vincent

2015-11-01

Radiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. An induction phase with two upfront courses of CCRT delivering a 40Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2-3 cycles of ESHAP chemotherapy alone. Thirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3-4 haematological toxicity. The main non-haematological grade 3-4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. With optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type. Copyright © 2015 Elsevier Ltd. All rights reserved.

ompW is cooperatively upregulated by MarA and SoxS in response to menadione

PubMed Central

Collao, B.; Morales, E. H.; Gil, F.; Calderón, I. L.

2013-01-01

OmpW is a minor porin whose biological function has not been clearly defined. Evidence obtained in our laboratory indicates that in Salmonella enterica serovar Typhimurium the expression of OmpW is activated by SoxS upon exposure to paraquat and it is required for resistance. SoxS belongs to the AraC family of transcriptional regulators, like MarA and Rob. Due to their high structural similarity, the genes under their control have been grouped in the mar/sox/rob regulon, which presents a DNA-binding consensus sequence denominated the marsox box. In this work, we evaluated the role of the transcription factors MarA, SoxS and Rob of S. enterica serovar Typhimurium in regulating ompW expression in response to menadione. We determined the transcript and protein levels of OmpW in different genetic backgrounds; in the wild-type and Δrob strains ompW was upregulated in response to menadione, while in the ΔmarA and ΔsoxS strains the induction was abolished. In a double marA soxS mutant, ompW transcript levels were lowered after exposure to menadione, and only complementation in trans with both genes restored the positive regulation. Using transcriptional fusions and electrophoretic mobility shift assays with mutant versions of the promoter region we demonstrated that two of the predicted sites were functional. Additionally, we demonstrated that MarA increases the affinity of SoxS for the ompW promoter region. In conclusion, our study shows that ompW is upregulated in response to menadione in a cooperative manner by MarA and SoxS through a direct interaction with the promoter region. PMID:23393149

ompW is cooperatively upregulated by MarA and SoxS in response to menadione.

PubMed

Collao, B; Morales, E H; Gil, F; Calderón, I L; Saavedra, C P

2013-04-01

OmpW is a minor porin whose biological function has not been clearly defined. Evidence obtained in our laboratory indicates that in Salmonella enterica serovar Typhimurium the expression of OmpW is activated by SoxS upon exposure to paraquat and it is required for resistance. SoxS belongs to the AraC family of transcriptional regulators, like MarA and Rob. Due to their high structural similarity, the genes under their control have been grouped in the mar/sox/rob regulon, which presents a DNA-binding consensus sequence denominated the marsox box. In this work, we evaluated the role of the transcription factors MarA, SoxS and Rob of S. enterica serovar Typhimurium in regulating ompW expression in response to menadione. We determined the transcript and protein levels of OmpW in different genetic backgrounds; in the wild-type and Δrob strains ompW was upregulated in response to menadione, while in the ΔmarA and ΔsoxS strains the induction was abolished. In a double marA soxS mutant, ompW transcript levels were lowered after exposure to menadione, and only complementation in trans with both genes restored the positive regulation. Using transcriptional fusions and electrophoretic mobility shift assays with mutant versions of the promoter region we demonstrated that two of the predicted sites were functional. Additionally, we demonstrated that MarA increases the affinity of SoxS for the ompW promoter region. In conclusion, our study shows that ompW is upregulated in response to menadione in a cooperative manner by MarA and SoxS through a direct interaction with the promoter region.

Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators

PubMed Central

Nock, Adam M.

2016-01-01

ABSTRACT Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa. Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa. Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis. In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. IMPORTANCE Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential regulation of these components can help us understand both the evolution of these systems and the potential roles these pathways have in the biology of each bacterium. Here, we describe the transcriptome response of Burkholderia thailandensis to the eukaryote-enriched molecule choline, identify the regulatory pathway governing choline catabolism, and compare the pathway to that previously described for Pseudomonas aeruginosa. These data support a multitiered regulatory network in B. thailandensis, with conserved orthologs in the select agents Burkholderia pseudomallei and Burkholderia mallei, as well as the opportunistic lung pathogens in the Burkholderia cepacia clade. PMID:27381916

Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators.

PubMed

Nock, Adam M; Wargo, Matthew J

2016-09-15

Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential regulation of these components can help us understand both the evolution of these systems and the potential roles these pathways have in the biology of each bacterium. Here, we describe the transcriptome response of Burkholderia thailandensis to the eukaryote-enriched molecule choline, identify the regulatory pathway governing choline catabolism, and compare the pathway to that previously described for Pseudomonas aeruginosa These data support a multitiered regulatory network in B. thailandensis, with conserved orthologs in the select agents Burkholderia pseudomallei and Burkholderia mallei, as well as the opportunistic lung pathogens in the Burkholderia cepacia clade. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Future Directions in Myelodysplastic Syndrome: Newer Agents and the Role of Combination Approaches

PubMed Central

Gore, Steven D.; Hermes-DeSantis, Evelyn R.

2009-01-01

Myelodysplastic syndrome (MDS) is not a single disease, but a collection of hematopoietic disorders that require newer strategies. Currently, azacitidine, decitabine, and lenalidomide are approved by the US Food and Drug Administration for the treatment of MDS. A recent study demonstrated an improved overall survival (24.4 months vs 15 months) in high-risk MDS patients receiving azacitidine plus best supportive care vs conventional care which has resulted in an updated label for this product. Conventional care consisted of supportive care alone or either low-dose ara-C or standard chemotherapy plus best supportive care. While these data are encouraging, newer agents such as vorinostat, MGCD0103, MS-275, and tipifarnib are currently being studied as monotherapy or in combinations with approved treatments for MDS. The goal of combining pharmacotherapy, such as the combination of DNA methylation inhibitors and histone deacetylase inhibitors, in the management of MDS is to increase the response rates and decrease the toxicities associated with treatment. Clinical experience in the use of combination products has given practitioners the empirical knowledge necessary to better treat patients with MDS. Utilizing convergent or complementary molecular mechanisms with in vitro or in vivo evidence of synergy is a fresher and maybe a more efficacious approach to combination therapy. PMID:18813208

Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice.

PubMed

Monteiro, Brisa M M; Moreira, Fabrício A; Massensini, André R; Moraes, Márcio F D; Pereira, Grace S

2014-02-01

Social memory consists of the information necessary to identify and recognize cospecifics and is essential to many forms of social interaction. Social memory persistence is strongly modulated by the animal's experiences. We have shown in previous studies that social isolation (SI) in adulthood impairs social memory persistence and that an enriched environment (EE) prevents this impairment. However, the mechanisms involved in the effects of SI and EE on social memory persistence remain unknown. We hypothesized that the mechanism by which SI and EE affect social memory persistence is through their modulation of neurogenesis. To investigate this hypothesis, adult mice were submitted to 7 days of one of the following conditions: group-housing in a standard (GH) or enriched environment (GH+EE); social isolation in standard (SI) or enriched environment (SI+EE). We observed an increase in the number of newborn neurons in the dentate gyrus of the hippocampus (DG) and glomerular layer of the olfactory bulb (OB) in both GH+EE and SI+EE mice. However, this increase of newborn neurons in the granule cell layer of the OB was restricted to the GH+EE group. Furthermore, both SI and SI+EE groups showed less neurogenesis in the mitral layer of the OB. Interestingly, the performance of the SI mice in the buried food-finding task was inferior to that of the GH mice. To further analyze whether increased neurogenesis is in fact the mechanism by which the EE improves social memory persistence in SI mice, we administered the mitotic inhibitor AraC or saline directly into the lateral ventricles of the SI+EE mice. We found that the AraC treatment decreased cell proliferation in both the DG and OB, and impaired social memory persistence in the SI+EE mice. Taken together, our results strongly suggest that neurogenesis is what supports social memory persistence in socially isolated mice. © 2013 Wiley Periodicals, Inc.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

PubMed Central

Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.

PubMed

Chen, Wen-Lian; Wang, Yue-Ying; Zhao, Aihua; Xia, Li; Xie, Guoxiang; Su, Mingming; Zhao, Linjing; Liu, Jiajian; Qu, Chun; Wei, Runmin; Rajani, Cynthia; Ni, Yan; Cheng, Zhen; Chen, Zhu; Chen, Sai-Juan; Jia, Wei

2016-11-14

Rapidly proliferating leukemic progenitor cells consume substantial glucose, which may lead to glucose insufficiency in bone marrow. We show that acute myeloid leukemia (AML) cells are prone to fructose utilization with an upregulated fructose transporter GLUT5, which compensates for glucose deficiency. Notably, AML patients with upregulated transcription of the GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of the antileukemic agent, Ara-C. In conclusion, this study highlights enhanced fructose utilization as a metabolic feature of AML and a potential therapeutic target. Copyright © 2016 Elsevier Inc. All rights reserved.

Temperature sensing in Yersinia pestis: regulation of yopE transcription by lcrF.

PubMed Central

Hoe, N P; Minion, F C; Goguen, J D

1992-01-01

In Escherichia coli, a yopE::lacZ fusion was found to be regulated by temperature in the presence of the cloned BamHI G fragment of Yersinia pestis plasmid pCD1, which contains the lcrF locus. Increasing the copy number of lcrF relative to that of the yopE reporter had a negligible effect on the induction ratio (26 versus 37 degrees C) but caused large reductions in the absolute levels of yopE transcription. We localized the lcrF gene by monitoring the induction phenotype of BamHI G deletion derivatives. Sequencing revealed an open reading frame capable of encoding a protein of 30.8 kDa. A protein product of this size was detected in a T7 expression system, and LcrF-dependent yopE-specific DNA binding activity was observed. As expected, LcrF exhibited 98% homology to VirF of Yersinia enterocolitica and significant homology to the carboxy termini of other members of the AraC family of transcriptional regulatory proteins. These proteins could be divided into two classes according to function: those regulating operons involved in catabolism of carbon and energy sources and those involved in regulating virulence genes. lcrF::lacZ transcriptional fusions were constructed and analyzed in Y. pestis and E. coli. The activity of the fusions was not affected by the native pCD1 virulence plasmid, an intact lcrF gene, or temperature. Thus, induction of lcrF transcription is not essential for temperature-dependent activation of yopE transcription. A portion of LcrF was found associated with the membrane fraction in E. coli; however, pulse-chase experiments indicated that this result is an artifact of fractionation. Images PMID:1624422

The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients.

PubMed

Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph

2015-08-01

To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; <1.9%; ALDH-rare AML), whereas 24 patients had relatively numerous ALDH(+) cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

[Neuron differential attachment purification and its influence factor].

PubMed

Li, Jun; Feng, Daxiong; Huang, Yize; Ye, Fei

2010-02-01

Neuron purification is essential to procedure of various nerve cell experimental research, however, at present there is few reports on the effect of various factors on neural axons during purification. To find out a simple method of neuron purification, and to investigate the influence factors of corresponding purification culture in dorsal root ganglion (DRG) tissue culture on beta3-tubulin positive axon. The DRGs were obtained from the 3 days neonatal SD rat microscopically and were made into cell suspension. Then, the amount of attached DRG neurons and nonneuronal cells in poly-D-lysine (PDL) group, PDL/Laminin (PDL/LN) group and collagen-I (Col I) group was observed from 10 to 100 minutes. Then, the extension and arborization of beta3-tubulin positive axons were observed after 72 hours completely randomised DRG tissue culture for the research of the influences among culture substrates (PDL, PDL/LN, and Col I), FBS (0, 5%, and 10%), 5 fluorouracil (5-Fu, 0, 20, and 40 micromol/L), and cytarabine (Ara-C, 0, 10, and 20 micromol/L). Adherent cells were observed instantly after inoculation by inverted phase contrast microscope and inverted fluorescence microscope; after cell suspension was removed, adherent growth of DRGn cells and non-DRGn cells were still seen. In PDL group, the amount of NSE negative cells was significantly higher than that of NSE positive cells at 10 and 30 minutes (P < 0.05); the amount of NSE positive cells was significantly higher than that of NSE negative cells at 80, 90 and 100 minutes (P < 0.05). In PDL/LN group, there was no significant difference (P > 0.05) in the amount of NSE negative cells and NSE positive cells at 10, 20, 30, 40, and 50 minutes; the amount of NSE positive cells was significantly higher (P < 0.05) than that of NSE negative cells at 60, 70, 80, 90, 100 minutes. In Col I group, the amount of NSE negative cells was higher than that of NSE positive cells at 10-40 minutes, but showing no significant difference (P > 0.05); the amount of NSE positive cells was significantly higher (P < 0.05) than that of NSE negative cells at 70-100 minutes. At 72 hours after DRG tissue culture, the best result of beta3-tubulin positive axon extension and arborization was obtained when the substrate level was PDL/LN, and the average length of PDL/LN level was significantly larger than that of other two substrates (P < 0.05). The highest number of beta3-tubulin positive axon distal end was obtained at 5% concentration level of FBS (P < 0.05), but showing no significant differences in beta3-tubulin positive axon length among three levels (P > 0.05). Both the most of beta3-tubulin positive axon distal ends and the longest beta3-tubulin positive axon average length were obtained at 0 micromol/L concentration level of 5-Fu, showing significant differences between 0 micromol/L level and 20, 40 micromol/L levels (P < 0.05). A similar result of 33-tubulin positive axon distal end was got at the 0 micromol/L level and 10 micromol/L level of Ara-C, which was significantly higher than that of 20 micromol/L level (P < 0.05). A purified DRG neuron suspension for neuron culture could be obtained via PDL differential attachment for 30 minutes. When DRG neuron culture, neuron special medium, PDL/LN substrate and 10 micromol/L Ara-C are recommended in beta3-tubulin positive axon research.

Purification and Properties of Cytidine Deaminase from Normal and Leukemic Granulocytes

PubMed Central

Chabner, Bruce A.; Johns, David G.; Coleman, C. Norman; Drake, James C.; Evans, Warren H.

1974-01-01

Cytidine deaminase, an enzyme that catalyses the deamination of both cytidine and its nucleoside analogues including the antineoplastic agents cytosine arabinoside (ara-C) and 5-azacytidine (5-azaC), has been partially purified from normal and leukemic human granulocytes. The purification procedure included heat precipitation at 70°C, ammonium sulfate precipitation, calcium phosphate gel ion exchange, and Sephadex G-150 gel filtration. The enzyme has mol wt 51,000, isoelectric pH of 4.8, and maximum activity over a broad pH range of 5-9.5. The enzyme is stabilized by the presence of the sulfhydryl reagent, dithiothreitol. Cytidine deaminase from normal human granulocytes has a greater affinity for its physiologic substrate cytidine (Km = 1.1 × 10−5 M) than for ara-C (8.8 × 10−5 M) or 5-azaC (4.3 × 10−4 M). Halogenated analogues such as 5-fluorocytidine and 5-bromo-2′-deoxycytidine also exhibited substrate activity, with maximum velocities greater than that of the physiologic substrates cytidine and deoxycytidine. No activity was observed with nucleotides or deoxynucleotides. The relative maximum velocity of the enzyme for cytidine and its nucleoside analogues remained constant during purification, indicating that a single enzyme was responsible for deamination of these substrates. Tetrahydrouridine (THU) was found to be a strong competitive inhibitor of partially purified deaminase with a Ki of 5.4 × 10−8 M. The biochemical properties of partially purified preparations of cytidine deaminase from normal and leukemic cells were compared with respect to isoelectric pH, molecular weight, and substrate and inhibitor kinetic parameters, and no differences were observed. However, normal circulating granulocytes contained a significantly greater concentration of cytidine deaminase (3.52±1.86 × 103/mg protein) than chronic myelocytic leukemia (CML) cells (1.40±0.70 × 103 U/mg protein) or acute myelocytic leukemia (AML) cells (0.19±0.17 × 103 U/mg protein). To explain these differences in enzyme levels in leukemic versus normal cells, the changes in cytidine deaminase levels associated with maturation of normal granulocytes were studied in normal human bone marrow. Myeloid precursors obtained from bone marrow aspirates were separated into mature and immature fractions by Ficoll density centrifugation. Deaminase activity in lysates of mature granulocytes was 3.55-14.2 times greater than the activity found in the lysates of immature cells. Decreased enzyme activity was also found in immature myeloid cells from a patient with CML as compared to mature granulocytes from the same patient. These observations support the conclusion that the greater specific activity of cytidine deaminase in normal mature granulocytes as compared to leukemic cells is related to the process of granulocyte maturation rather than a specific enzymatic defect in leukemic cells. PMID:4521417

Critical systems for public health management of floods, North Dakota.

PubMed

Wiedrich, Tim W; Sickler, Juli L; Vossler, Brenda L; Pickard, Stephen P

2013-01-01

Availability of emergency preparedness funding between 2002 and 2009 allowed the North Dakota Department of Health to build public health response capabilities. Five of the 15 public health preparedness capability areas identified by the Centers for Disease Control and Prevention in 2011 have been thoroughly tested by responses to flooding in North Dakota in 2009, 2010, and 2011; those capability areas are information sharing, emergency operations coordination, medical surge, material management and distribution, and volunteer management. Increasing response effectiveness has depended on planning, implementation of new information technology, changes to command and control procedures, containerized response materials, and rapid contract procedures. Continued improvement in response and maintenance of response capabilities is dependent on ongoing funding.

Mimicking phosphorylation of Ser-74 on human deoxycytidine kinase selectively increases catalytic activity for dC and dC analogues.

PubMed

McSorley, Theresa; Ort, Stephan; Hazra, Saugata; Lavie, Arnon; Konrad, Manfred

2008-03-05

Intracellular phosphorylation of dCK on Ser-74 results in increased nucleoside kinase activity. We mimicked this phosphorylation by a Ser-74-Glu mutation in bacterially produced dCK and investigated kinetic parameters using various nucleoside substrates. The S74E mutation increases the k(cat) values 11-fold for dC, and 3-fold for the anti-cancer analogues dFdC and AraC. In contrast, the rate is decreased for the purine substrates. In HEK293 cells, we found that by comparing transiently transfected dCK(S74E)-GFP and wild-type dCK-GFP, mimicking the phosphorylation of Ser-74 has no effect on cellular localisation. We note that phosphorylation may represent a mechanism to enhance the catalytic activity of the relatively slow dCK enzyme.

Self-reported Preparedness to Respond to Mass Fatality Incidents in 38 State Health Departments.

PubMed

Merrill, Jacqueline; Zhi, Qi; Gershon, Robyn R

Public health departments play an important role in the preparation and response to mass fatality incidents (MFIs). To describe MFI response capabilities of US state health departments. The data are part of a multisector cross-sectional study aimed at 5 sectors that comprise the US mass fatality infrastructure. Data were collected over a 6-week period via a self-administered, anonymous Web-based survey. In 2014, a link to the survey was distributed via e-mail to health departments in 50 states and the District of Columbia. State health department representatives responsible for their state's MFI plans. Preparedness was assessed using 3 newly developed metrics: organizational capabilities (n = 19 items); operational capabilities (n = 19 items); and resource-sharing capabilities (n = 13 items). Response rate was 75% (n = 38). Among 38 responses, 37 rated their workplace moderately or well prepared; 45% reported MFI training, but only 30% reported training on MFI with hazardous contaminants; 58% estimated high levels of staff willingness to respond, but that dropped to 40% if MFIs involved hazardous contaminants; and 84% reported a need for more training. On average, 76% of operational capabilities were present. Resource sharing was most prevalent with state Office of Emergency Management but less evident with faith-based organizations and agencies within the medical examiner sector. Overall response capability was adequate, with gaps found in capabilities where public health shares responsibility with other sectors. Collaborative training with other sectors is critical to ensure optimal response to future MFIs, but recent funding cuts in public health preparedness may adversely impact this critical preparedness element. In order for the sector to effectively meet its public health MFI responsibilities as delineated in the National Response Framework, resources to support training and other elements of preparedness must be maintained.

Unmanned and Unattended Response Capability for Homeland Defense

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

BENNETT, PHIL C.

2002-11-01

An analysis was conducted of the potential for unmanned and unattended robotic technologies for forward-based, immediate response capabilities that enables access and controlled task performance. The authors analyze high-impact response scenarios in conjunction with homeland security organizations, such as the NNSA Office of Emergency Response, the FBI, the National Guard, and the Army Technical Escort Unit, to cover a range of radiological, chemical and biological threats. They conducted an analysis of the potential of forward-based, unmanned and unattended robotic technologies to accelerate and enhance emergency and crisis response by Homeland Defense organizations. Response systems concepts were developed utilizing new technologiesmore » supported by existing emerging threats base technologies to meet the defined response scenarios. These systems will pre-position robotic and remote sensing capabilities stationed close to multiple sites for immediate action. Analysis of assembled systems included experimental activities to determine potential efficacy in the response scenarios, and iteration on systems concepts and remote sensing and robotic technologies, creating new immediate response capabilities for Homeland Defense.« less

Capabilities of electrodynamic shakers when used for mechanical shock testing

NASA Technical Reports Server (NTRS)

Keegan, W. B.

1973-01-01

The results of a research task to investigate the capabilities of electrodynamic vibrators (shakers) to perform mechanical shock tests are presented. The simulation method employed was that of developing a transient whose shock response spectrum matched the desired shock response spectrum. Areas investigated included the maximum amplitude capabilities of the shaker systems, the ability to control the shape of the resultant shock response spectrum, the response levels induced at frequencies outside the controlled bandwidth, and the nonlinearities in structural response induced by a change in test level.

Annual Report to The President and The Congress of the Advisory Panel to Assess Domestic Response Capabilities for Terrorism Involving Weapons of Mass Destruction (2nd). II. Toward a National Strategy for Combating Terrorism

DTIC Science & Technology

2000-12-15

over many years, for responses to natural disasters, disease outbreaks, and accidents. Those capabilities can and should be used as a base for...terminated. 57 Many response entities had used those services and had included that capability in their response plans. This is one more example of... Many Federal entities 58 conduct or facilitate various exercises and offer State and local response entities opportunities to participate. Most agencies

Progenitor cell dynamics in the Newt Telencephalon during homeostasis and neuronal regeneration.

PubMed

Kirkham, Matthew; Hameed, L Shahul; Berg, Daniel A; Wang, Heng; Simon, András

2014-04-08

The adult newt brain has a marked neurogenic potential and is highly regenerative. Ventricular, radial glia-like ependymoglia cells give rise to neurons both during normal homeostasis and after injury, but subpopulations among ependymoglia cells have not been defined. We show here that a substantial portion of GFAP(+) ependymoglia cells in the proliferative hot spots of the telencephalon has transit-amplifying characteristics. In contrast, proliferating ependymoglia cells, which are scattered along the ventricular wall, have stem cell features in terms of label retention and insensitivity to AraC treatment. Ablation of neurons remodels the proliferation dynamics and leads to de novo formation of regions displaying features of neurogenic niches, such as the appearance of cells with transit-amplifying features and proliferating neuroblasts. The results have implication both for our understanding of the evolutionary diversification of radial glia cells as well as the processes regulating neurogenesis and regeneration in the adult vertebrate brain.

Mimicking phosphorylation of Ser-74 on human deoxycytidine kinase selectively increases catalytic activity for dC and dC analogues

PubMed Central

McSorley, Theresa; Ort, Stephan; Hazra, Saugata; Lavie, Arnon; Konrad, Manfred

2009-01-01

Intracellular phosphorylation of dCK on Ser-74 results in increased nucleoside kinase activity. We mimicked this phosphorylation by a Ser-74-Glu mutation in bacterially produced dCK and investigated kinetic parameters using various nucleoside substrates. The S74E mutation increases the kcat values 11-fold for dC, and 3-fold for the anti-cancer analogues dFdC and AraC. In contrast, the rate is decreased for the purine substrates. In HEK293 cells, we found that by comparing transiently transfected dCK(S74E)-GFP and wild-type dCK-GFP, mimicking the phosphorylation of Ser-74 has no effect on cellular localisation. We note that phosphorylation may represent a mechanism to enhance the catalytic activity of the relatively slow dCK enzyme. PMID:18258203

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

PubMed Central

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity. PMID:28659796

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

PubMed

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche

PubMed Central

Mohammad, H; Marchisella, F; Ortega-Martinez, S; Hollos, P; Eerola, K; Komulainen, E; Kulesskaya, N; Freemantle, E; Fagerholm, V; Savontous, E; Rauvala, H; Peterson, B D; van Praag, H; Coffey, E T

2018-01-01

Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders. PMID:27843149

Chemical sensors

DOEpatents

Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.

1991-01-01

Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising (a) a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, operatively coupled to (b) a transducer capable of directly converting said expansion or contraction to a measurable electrical response.

Development, Verification and Validation of Enclosure Radiation Capabilities in the CHarring Ablator Response (CHAR) Code

NASA Technical Reports Server (NTRS)

Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.

2016-01-01

With the recent development of multi-dimensional thermal protection system (TPS) material response codes including the capabilities to account for radiative heating is a requirement. This paper presents the recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute view factors for radiation problems involving multiple surfaces. Furthermore, verification and validation of the code's radiation capabilities are demonstrated by comparing solutions to analytical results, to other codes, and to radiant test data.

Chemical sensors

DOEpatents

Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.

1991-07-02

Sensors responsive to small changes in the concentration of chemical species are disclosed. The sensors comprise a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment. They are operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical response. 9 figures.

NASA's Applied Sciences: Natural Disasters Program

NASA Technical Reports Server (NTRS)

Kessler, Jason L.

2010-01-01

Fully utilize current and near-term airborne and spaceborne assets and capabilities. NASA spaceborne instruments are for research but can be applied to natural disaster response as appropriate. NASA airborne instruments can be targeted specifically for disaster response. Could impact research programs. Better flow of information improves disaster response. Catalog capability, product, applicable disaster, points of contact. Ownership needs to come from the highest level of NASA - unpredictable and irregular nature of disasters requires contingency funding for disaster response. Build-in transfer of applicable natural disaster research capabilities to operational functionality at other agencies (e.g., USFS, NOAA, FEMA...) at the outset, whenever possible. For the Decadal Survey Missions, opportunities exist to identify needs and requirements early in the mission design process. Need to understand additional needs and commitments for meeting the needs of the disaster community. Opportunity to maximize disaster response and mitigation from the Decadal Survey Missions. Additional needs or capabilities may require agency contributions.

A Highly Capable Year 6 Student's Response to a Challenging Mathematical Task

ERIC Educational Resources Information Center

Livy, Sharyn; Holmes, Marilyn; Ingram, Naomi; Linsell, Chris; Sullivan, Peter

2016-01-01

Highly capable mathematics students are not usually considered strugglers. This paper reports on a case study of a Year 6 student, Debbie, her response to a lesson, and her learning involving a challenging mathematical task. Debbie, usually a highly capable student, struggled to complete a challenging mathematical task by herself, but as the…

Aviation System Analysis Capability Quick Response System Report for Fiscal Year 1998

NASA Technical Reports Server (NTRS)

Ege, Russell; Villani, James; Ritter, Paul

1999-01-01

This document presents the additions and modifications made to the Quick Response System (QRS) in FY 1998 in support of the ASAC QRS development effort. this Document builds upon the Aviation System Analysis Capability Quick Responses System Report for Fiscal Year 1997.

Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4;#8201;Å

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

Johnson, Zachary Lee; Cheong, Cheom-Gil; Lee, Seok-Yong

2012-07-11

Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine has a function in a variety of signalling processes. Transport of nucleosides across cell membranes provides the major source of nucleosides in many cell types and is also responsible for the termination of adenosine signalling. As a result of their hydrophilic nature, nucleosides require a specialized class of integral membrane proteins, known as nucleoside transporters (NTs), for specific transport across cell membranes. In addition to nucleosides, NTs are important determinants for the transport of nucleoside-derived drugs across cell membranes. A wide range of nucleoside-derived drugs, including anticancer drugsmore » (such as Ara-C and gemcitabine) and antiviral drugs (such as zidovudine and ribavirin), have been shown to depend, at least in part, on NTs for transport across cell membranes. Concentrative nucleoside transporters, members of the solute carrier transporter superfamily SLC28, use an ion gradient in the active transport of both nucleosides and nucleoside-derived drugs against their chemical gradients. The structural basis for selective ion-coupled nucleoside transport by concentrative nucleoside transporters is unknown. Here we present the crystal structure of a concentrative nucleoside transporter from Vibrio cholerae in complex with uridine at 2.4 {angstrom}. Our functional data show that, like its human orthologues, the transporter uses a sodium-ion gradient for nucleoside transport. The structure reveals the overall architecture of this class of transporter, unravels the molecular determinants for nucleoside and sodium binding, and provides a framework for understanding the mechanism of nucleoside and nucleoside drug transport across cell membranes.« less

Development and Verification of Enclosure Radiation Capabilities in the CHarring Ablator Response (CHAR) Code

NASA Technical Reports Server (NTRS)

Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.

2016-01-01

With the recent development of multi-dimensional thermal protection system (TPS) material response codes, the capability to account for surface-to-surface radiation exchange in complex geometries is critical. This paper presents recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute geometric view factors for radiation problems involving multiple surfaces. Verification of the code's radiation capabilities and results of a code-to-code comparison are presented. Finally, a demonstration case of a two-dimensional ablating cavity with enclosure radiation accounting for a changing geometry is shown.

Strengthening the Federal Emergency Management Agency's disaster response capabilities.

PubMed

Cannon, Glenn M

2008-04-01

The Federal Emergency Management Agency's (FEMA) Disaster Operations Directorate provides the core federal response capability to save lives and to protect property in US communities that have been overwhelmed by the impact of a major disaster or emergency. The directorate executes its mission through three main programme areas: operational direction, command and control; operational teams; and operational planning. Based on lessons learned from years of disaster response experience, FEMA is now taking a more proactive and collaborative approach with its partners. This paper discusses how FEMA is placing a greater emphasis on response operations and strengthening capabilities across the full range of operational and support missions by comprehensively revamping its disaster operations model; enhancing its headquarters and regional operations centres; enhancing its headquarters and regional operational planning capabilities; and addressing catastrophic disaster planning and related critical preparedness issues.

Chemical sensors

DOEpatents

Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.

1992-01-01

Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material.

Chemical sensors

DOEpatents

Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.

1992-06-09

Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material. 12 figs.

Viral Vaccine Immunogenicity in Relation to Host Cell-Mediated and Humoral Immune Responses.

DTIC Science & Technology

1976-05-01

adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring adoptive immunity...vac- cine combined with adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring...Freund’s adjuvant and Bordetella pertussis , are consistently capable of producing early and brisk serum neutralizing antibody responses in adoptively

A capability model of individual differences in frontal EEG asymmetry.

PubMed

Coan, James A; Allen, John J B; McKnight, Patrick E

2006-05-01

Researchers interested in measuring individual differences in affective style via asymmetries in frontal brain activity have depended almost exclusively upon the resting state for EEG recording. This reflects an implicit conceptualization of affective style as a response predisposition that is manifest in frontal EEG asymmetry, with the goal to describe individuals in terms of their general approach or withdrawal tendencies. Alternatively, the response capability conceptualization seeks to identify individual capabilities for approach versus withdrawal responses during emotionally salient events. The capability approach confers a variety of advantages to the study of affective style and personality, and suggests new possibilities for the approach/withdrawal motivational model of frontal EEG asymmetry and emotion. Logical as well as empirical arguments supportive of this conclusion are presented.

Methotrexate and Cytarabine-Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study.

PubMed

Pentak, Danuta; Kozik, Violetta; Bąk, Andrzej; Dybał, Paulina; Sochanik, Aleksander; Jampilek, Josef

2016-12-08

Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC) interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance 2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR) were consistent with the results obtained by Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR).

Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

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

Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria

2010-03-04

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding thatmore » cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.« less

Sustaining Statewide Disaster Response Capabilities from a Fire Service Perspective

DTIC Science & Technology

2013-03-01

2010). These increased capabilities can be vital to the success of response operations that involve automobile accidents, train wrecks , boat...Trench Rescue  Subterranean Rescue  Dive Rescue  Wilderness Rescue 2. 1670 Operations and Training for Technical Search and Rescue Incidents The

Response capabilities of the National Guard: a focus on domestic disaster medical response.

PubMed

Bochicchio, Daniel

2010-01-01

The National Guard has a 373-year history of responding to the nation's call to duty for service both at home and abroad (The National Guard Bureau Web site: Available at http://www.ngb.army.mil/default. aspx.). The National Guard (NG) is a constitutionally unique organization (United States Constitution, US Government Printing Office Web site: Available at http://www.gpoaccess.gov/constitution/index.html.). Today's Guard conducts domestic disaster response and civilian assistance missions on a daily basis. Yet, the NG's role, mission, and capabilities are not well-known or understood. The National Response Framework (NRF) places significant responsibility on the local and state disaster planners (Department of Homeland Security: National Response Framework. US Department of Homeland Security, Washington, DC, January 2008). The public health professionals are an integral component of the disaster planning community. It is critical that the public health community be knowledgeable of types and capabilities of all the response assets at their disposal.

A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia.

PubMed

Burnett, A K; Russell, N H; Hills, R K; Kell, J; Nielsen, O J; Dennis, M; Cahalin, P; Pocock, C; Ali, S; Burns, S; Freeman, S; Milligan, D; Clark, R E

2017-02-01

The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance. The primary end point was overall survival. The overall response rate was 69% (complete remission (CR) 60%; CRi 9%), with no difference between DA (71%) and DClo (66%). There was no difference in 30-/60-day mortality or toxicity: significantly more supportive care was required in the DA arm even though platelet and neutrophil recovery was significantly slower with DClo. There were no differences in cumulative incidence of relapse (74% vs 68%; hazard ratio (HR) 0.93 (0.77-1.14), P=0.5); survival from relapse (7% vs 9%; HR 0.96 (0.77-1.19), P=0.7); relapse-free (31% vs 32%; HR 1.02 (0.83-1.24), P=0.9) or overall survival (23% vs 22%; HR 1.08 (0.93-1.26), P=0.3). Clofarabine 20 mg/m 2 given for 5 days with daunorubicin is not superior to ara-C+daunorubicin as induction for older patients with AML/high-risk MDS.

Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach.

PubMed

Desai, Urja N; Shah, Krupa P; Mirza, Sheefa H; Panchal, Darshil K; Parikh, Sonia K; Rawal, Rakesh M

2015-01-01

Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patient's bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 μM-100 μM) and Silibinin (0.5 μM-100 μM) alone and in combination with Cytarabine (Hesperidin-25 μM, Silibinin10 μM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method. In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 μM and 16.2 μM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents.

A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia

PubMed Central

Burnett, A K; Russell, N H; Hills, R K; Kell, J; Nielsen, O J; Dennis, M; Cahalin, P; Pocock, C; Ali, S; Burns, S; Freeman, S; Milligan, D; Clark, R E

2017-01-01

The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56–84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance. The primary end point was overall survival. The overall response rate was 69% (complete remission (CR) 60% CRi 9%), with no difference between DA (71%) and DClo (66%). There was no difference in 30-/60-day mortality or toxicity: significantly more supportive care was required in the DA arm even though platelet and neutrophil recovery was significantly slower with DClo. There were no differences in cumulative incidence of relapse (74% vs 68% hazard ratio (HR) 0.93 (0.77–1.14), P=0.5); survival from relapse (7% vs 9% HR 0.96 (0.77–1.19), P=0.7); relapse-free (31% vs 32% HR 1.02 (0.83–1.24), P=0.9) or overall survival (23% vs 22% HR 1.08 (0.93–1.26), P=0.3). Clofarabine 20 mg/m2 given for 5 days with daunorubicin is not superior to ara-C+daunorubicin as induction for older patients with AML/high-risk MDS. PMID:27624670

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

PubMed

Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

2017-07-01

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Microbial Relatives of the Seed Storage Proteins of Higher Plants: Conservation of Structure and Diversification of Function during Evolution of the Cupin Superfamily

PubMed Central

Dunwell, Jim M.; Khuri, Sawsan; Gane, Paul J.

2000-01-01

This review summarizes the recent discovery of the cupin superfamily (from the Latin term “cupa,” a small barrel) of functionally diverse proteins that initially were limited to several higher plant proteins such as seed storage proteins, germin (an oxalate oxidase), germin-like proteins, and auxin-binding protein. Knowledge of the three-dimensional structure of two vicilins, seed proteins with a characteristic β-barrel core, led to the identification of a small number of conserved residues and thence to the discovery of several microbial proteins which share these key amino acids. In particular, there is a highly conserved pattern of two histidine-containing motifs with a varied intermotif spacing. This cupin signature is found as a central component of many microbial proteins including certain types of phosphomannose isomerase, polyketide synthase, epimerase, and dioxygenase. In addition, the signature has been identified within the N-terminal effector domain in a subgroup of bacterial AraC transcription factors. As well as these single-domain cupins, this survey has identified other classes of two-domain bicupins including bacterial gentisate 1,2-dioxygenases and 1-hydroxy-2-naphthoate dioxygenases, fungal oxalate decarboxylases, and legume sucrose-binding proteins. Cupin evolution is discussed from the perspective of the structure-function relationships, using data from the genomes of several prokaryotes, especially Bacillus subtilis. Many of these functions involve aspects of sugar metabolism and cell wall synthesis and are concerned with responses to abiotic stress such as heat, desiccation, or starvation. Particular emphasis is also given to the oxalate-degrading enzymes from microbes, their biological significance, and their value in a range of medical and other applications. PMID:10704478

A Highly-Conserved Single-Stranded DNA-Binding Protein in Xanthomonas Functions as a Harpin-Like Protein to Trigger Plant Immunity

PubMed Central

Che, Yi-Zhou; Zou, Li-Fang; Zakria, Muhammad; Zou, Hua-Song; Chen, Gong-You

2013-01-01

Harpins are produced by Gram-negative phytopathogenic bacteria and typically elicit hypersensitive response (HR) in non-host plants. The characterization of harpins in Xanthomonas species is largely unexplored. Here we demonstrate that Xanthomonas produce a highly conserved single-stranded DNA-binding protein (SSBX) that elicits HR in tobacco as by harpin Hpa1. SSBX, like Hpa1, is an acidic, glycine-rich, heat-stable protein that lacks cysteine residues. SSBX-triggered HR in tobacco, as by Hpa1, is characterized by the oxidative burst, the expression of HR markers (HIN1, HSR203J), pathogenesis-related genes, and callose deposition. Both SSBX- and Hpa1-induced HRs can be inhibited by general metabolism inhibitors actinomycin D, cycloheximide, and lanthanum chloride. Furthermore, those HRs activate the expression of BAK1 and BIK1 genes that are essential for induction of mitogen-activated protein kinase (MAPK) and salicylic acid pathways. Once applied to plants, SSBX induces resistance to the fungal pathogen Alternaria alternata and enhances plant growth. When ssbX was deleted in X. oryzae pv. oryzicola, the causal agent of bacterial leaf streak in rice, the resulting ssbXoc mutant was reduced in virulence and bacterial growth in planta, but retained its ability to trigger HR in tobacco. Interestingly, ssbXoc contains an imperfect PIP-box (plant-inducible promoter) and the expression of ssbXoc is regulated by HrpX, which belongs to the AraC family of transcriptional activators. Immunoblotting evidence showed that SSBx secretion requires a functional type-III secretion system as Hpa1 does. This is the first report demonstrating that Xanthomonas produce a highly-conserved SSBX that functions as a harpin-like protein for plant immunity. PMID:23418541

Formulation of a parametric systems design framework for disaster response planning

NASA Astrophysics Data System (ADS)

Mma, Stephanie Weiya

The occurrence of devastating natural disasters in the past several years have prompted communities, responding organizations, and governments to seek ways to improve disaster preparedness capabilities locally, regionally, nationally, and internationally. A holistic approach to design used in the aerospace and industrial engineering fields enables efficient allocation of resources through applied parametric changes within a particular design to improve performance metrics to selected standards. In this research, this methodology is applied to disaster preparedness, using a community's time to restoration after a disaster as the response metric. A review of the responses from Hurricane Katrina and the 2010 Haiti earthquake, among other prominent disasters, provides observations leading to some current capability benchmarking. A need for holistic assessment and planning exists for communities but the current response planning infrastructure lacks a standardized framework and standardized assessment metrics. Within the humanitarian logistics community, several different metrics exist, enabling quantification and measurement of a particular area's vulnerability. These metrics, combined with design and planning methodologies from related fields, such as engineering product design, military response planning, and business process redesign, provide insight and a framework from which to begin developing a methodology to enable holistic disaster response planning. The developed methodology was applied to the communities of Shelby County, TN and pre-Hurricane-Katrina Orleans Parish, LA. Available literature and reliable media sources provide information about the different values of system parameters within the decomposition of the community aspects and also about relationships among the parameters. The community was modeled as a system dynamics model and was tested in the implementation of two, five, and ten year improvement plans for Preparedness, Response, and Development capabilities, and combinations of these capabilities. For Shelby County and for Orleans Parish, the Response improvement plan reduced restoration time the most. For the combined capabilities, Shelby County experienced the greatest reduction in restoration time with the implementation of Development and Response capability improvements, and for Orleans Parish it was the Preparedness and Response capability improvements. Optimization of restoration time with community parameters was tested by using a Particle Swarm Optimization algorithm. Fifty different optimized restoration times were generated using the Particle Swarm Optimization algorithm and ranked using the Technique for Order Preference by Similarity to Ideal Solution. The optimization results indicate that the greatest reduction in restoration time for a community is achieved with a particular combination of different parameter values instead of the maximization of each parameter.

National health and medical services response to incidents of chemical and biological terrorism.

PubMed

Tucker, J B

1997-08-06

In response to the growing threat of terrorism with chemical and biological weapons, the US government has developed a national concept of operations for emergency health and medical services response. This capability was developed and tested for the first time during the Atlanta Olympic Games in the summer of 1996. In the event of a chemical or biological terrorist incident that exceeded local and state-level response capabilities, federal agencies would provide specialized teams and equipment to help manage the consequences of the attack and treat, decontaminate, and evacuate casualties. The US Congress has also established a Domestic Preparedness Program that provides for enhanced training of local first-responders and the formation of metropolitan medical strike teams in major cities around the country. While these national response capabilities are promising, their implementation to date has been problematic and their ultimate effectiveness is uncertain.

Responsibility, capability, and Active SETI: Policy, law, ethics, and communication with extraterrestrial intelligence

NASA Astrophysics Data System (ADS)

Vakoch, Douglas A.

2011-02-01

With recently growing interest in the Active Search for Extraterrestrial Intelligence (SETI), in which humankind would send intentional signals to extraterrestrial civilizations, there have been increased concerns about appropriate policy, as well as the role of space law and ethics in guiding such activities. Implicit in these discussions are notions of responsibility and capability that affect judgments about whether humans or other civilizations should initiate transmissions. Existing protocols that guide SETI research address transmissions from Earth, but there is debate over whether these guidelines should inform de novo transmissions as well. Relevant responsibilities to address include (1) looking out for the interests of humankind as a whole, (2) being truthful in interstellar messages, and (3) benefiting extraterrestrial civilizations. Our capabilities as a species and a civilization affect how well we can fulfill responsibilities, as seen when we consider whether we will be able to reach consensus about message contents (and whether that would be desirable), and whether we have the capacity to decode messages from beings that rely on different sensory modalities. The interplay of these responsibilities and capabilities suggests that humankind should place increased emphasis on Active SETI.

Time Dependent Data Mining in RAVEN

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

Cogliati, Joshua Joseph; Chen, Jun; Patel, Japan Ketan

RAVEN is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. The goal of this type of analyses is to understand the response of such systems in particular with respect their probabilistic behavior, to understand their predictability and drivers or lack of thereof. Data mining capabilities are the cornerstones to perform such deep learning of system responses. For this reason static data mining capabilities were added last fiscal year (FY 15). In real applications, when dealing with complex multi-scale, multi-physics systems it seems natural that, during transients, the relevance of themore » different scales, and physics, would evolve over time. For these reasons the data mining capabilities have been extended allowing their application over time. In this writing it is reported a description of the new RAVEN capabilities implemented with several simple analytical tests to explain their application and highlight the proper implementation. The report concludes with the application of those newly implemented capabilities to the analysis of a simulation performed with the Bison code.« less

Adult English Language Learners' Perceptions of Audience Response Systems (Clickers) as Communication Aides: A Q-Methodology Study

ERIC Educational Resources Information Center

Rodriguez, Lisa Ann; Shepard, MaryFriend

2013-01-01

This study explored the perceptions of adult English language learners about audience response systems (clickers) as tools to facilitate communication. According to second language acquisition theory, learners' receptive capabilities in the early stages of second language acquisition surpass expressive capabilities, often rendering them silent in…

Ship Response Capability Models for Counter-Piracy Patrols in the Gulf of Aden

DTIC Science & Technology

2011-09-01

exhibit one of six possible readiness states that can fit into one of four categories 8: (a) All helicopters at high alert level ( HHH ) (b) Two...Coordinated 30 min Uncoordinated 30 min Coordinated Figure 16: Effect of helicopter readiness on response capabilities. configurations HHH , HHL and HLH

A survey of pandemic influenza preparedness and response capabilities in Chicago area hospital security departments.

PubMed

Kimmerly, David P

2009-01-01

This article is a summary based on a December 2007 paper prepared by the author in partial fulfillment of the requirements for a master's degree in business and organizational security management at Webster University. The project described was intended to assess Chicago-area healthcare organization security departments' preparedness and response capabilities for a potential influenza pandemic. While the author says healthcare organizations are learning from the pandemics of the past, little research has been conducted on the requirements necessary within hospital security departments. The article explores staffing, planning, preparation and response capabilities within a healthcare security context to determine existing resources available to the healthcare security community. Eleven completed surveys were received from hospital security managers throughout the geographical Chicago area. They reveal that hospital security managers are conscious of the risks of a pandemic influenza outbreak. Yet, it was found that several gaps existed within hospital security department staffing and response capabilities, as hospital security departments may not have the available resources necessary to adequately maintain their operations during a pandemic incident.

In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

PubMed Central

Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

2016-01-01

The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

48 CFR 253.209-1 - Responsible prospective contractors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... required service. (B) Production capability. An evaluation of the prospective contractor's ability to plan.... (C) Quality assurance capability. An assessment of the prospective contractor's capability to meet the quality assurance requirements of the proposed contract. It may involve an evaluation of the...

Environmentally Responsible Aviation Project: Infrastructure Enhancements and New Capabilities

NASA Technical Reports Server (NTRS)

Bezos-OConnor, Gaudy M.

2015-01-01

This oral presentation highlights the technical investments the NASA Environmentally Responsible Aviation Project under the Integrated Systems Research Program within ARMD made during FY10-FY14 to upgrade/enhance the NASA infrastructure/testing assets and new capabilities required to mature the ERA N=2 Portfolio of airframe and propulsion technologies to TRL 5/6.

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

Brouillette, Greg A.

These are slides for various presentations on C41SR and urban disasters disasters response and recovery tools. These are all mainly charts and images of disaster response and recovery tools. Slides included have headings such as the following: vignette of a disaster response, situational awareness and common operating picture available to EOC, plume modeling capability, Program ASPECT Chemical Response Products, EPA ASPECT - Hurricane RITA Response 9/25/2005, Angel Fire Imagery, incident commander's view/police chief's view/ EMS' view, common situational awareness and collaborative planning, exercise, training capability, systems diagram, Austere Challenge 06 Sim/C4 Requirements, common situational awareness and collaborative planning, exercise, trainingmore » environment, common situational awareness, real world, crisis response, and consequence management.« less

Demand Response For Power System Reliability: FAQ

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

Kirby, Brendan J

2006-12-01

Demand response is the most underutilized power system reliability resource in North America. Technological advances now make it possible to tap this resource to both reduce costs and improve. Misconceptions concerning response capabilities tend to force loads to provide responses that they are less able to provide and often prohibit them from providing the most valuable reliability services. Fortunately this is beginning to change with some ISOs making more extensive use of load response. This report is structured as a series of short questions and answers that address load response capabilities and power system reliability needs. Its objective is tomore » further the use of responsive load as a bulk power system reliability resource in providing the fastest and most valuable ancillary services.« less

Semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon; Bruchez, Marcel; Alivisatos, Paul

2014-01-28

A semiconductor nanocrystal compound and probe are described. The compound is capable of linking to one or more affinity molecules. The compound comprises (1) one or more semiconductor nanocrystals capable of, in response to exposure to a first energy, providing a second energy, and (2) one or more linking agents, having a first portion linked to the one or more semiconductor nanocrystals and a second portion capable of linking to one or more affinity molecules. One or more semiconductor nanocrystal compounds are linked to one or more affinity molecules to form a semiconductor nanocrystal probe capable of bonding with one or more detectable substances in a material being analyzed, and capable of, in response to exposure to a first energy, providing a second energy. Also described are processes for respectively: making the semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and treating materials with the probe.

Semiconductor nanocrystal probes for biological applications and process for making and using such probes

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

Weiss, Shimon; Bruchez, Marcel; Alivisatos, Paul A.

2016-12-27

A semiconductor nanocrystal compound and probe are described. The compound is capable of linking to one or more affinity molecules. The compound comprises (1) one or more semiconductor nanocrystals capable of, in response to exposure to a first energy, providing a second energy, and (2) one or more linking agents, having a first portion linked to the one or more semiconductor nanocrystals and a second portion capable of linking to one or more affinity molecules. One or more semiconductor nanocrystal compounds are linked to one or more affinity molecules to form a semiconductor nanocrystal probe capable of bonding with onemore » or more detectable substances in a material being analyzed, and capable of, in response to exposure to a first energy, providing a second energy. Also described are processes for respectively: making the semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and treating materials with the probe.« less

76 FR 4708 - Agency Information Collection Activities: Submission for OMB Review; Comment Request, OMB No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... assess disaster logistics planning and response capabilities and identify areas of relative strength and...; Logistics Capability Assessment Tool (LCAT) AGENCY: Federal Emergency Management Agency, DHS. ACTION: Notice...: Collection of Information Title: Logistics Capability Assessment Tool (LCAT). Type of Information Collection...

Comprehensive Micromechanics-Analysis Code - Version 4.0

NASA Technical Reports Server (NTRS)

Arnold, S. M.; Bednarcyk, B. A.

2005-01-01

Version 4.0 of the Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC) has been developed as an improved means of computational simulation of advanced composite materials. The previous version of MAC/GMC was described in "Comprehensive Micromechanics-Analysis Code" (LEW-16870), NASA Tech Briefs, Vol. 24, No. 6 (June 2000), page 38. To recapitulate: MAC/GMC is a computer program that predicts the elastic and inelastic thermomechanical responses of continuous and discontinuous composite materials with arbitrary internal microstructures and reinforcement shapes. The predictive capability of MAC/GMC rests on a model known as the generalized method of cells (GMC) - a continuum-based model of micromechanics that provides closed-form expressions for the macroscopic response of a composite material in terms of the properties, sizes, shapes, and responses of the individual constituents or phases that make up the material. Enhancements in version 4.0 include a capability for modeling thermomechanically and electromagnetically coupled ("smart") materials; a more-accurate (high-fidelity) version of the GMC; a capability to simulate discontinuous plies within a laminate; additional constitutive models of materials; expanded yield-surface-analysis capabilities; and expanded failure-analysis and life-prediction capabilities on both the microscopic and macroscopic scales.

The use of polliniferous resources by Melipona capixaba, an endangered stingless bee species.

PubMed

Serra, Bruna Danielle Vieira; da Luz, Cynthia Fernandes Pinto; Campos, Lucio Antonio de Oliveira

2012-01-01

Abstract Pollen types present in samples from corbiculae of Melipona capixaba (Moure and Camargo) (Hymenoptera: Apidae: Meliponina) worker bees were analyzed, as well as pollen samples from food pots inside the hives in three sites located at the bees' original habitat. The aim was to find out the sources used as a trophic resource by this species. The dominant pollen grains in the spectrum of the samples belonged to the families Myrtaceae and Melastomataceae. Eucalyptus was the most frequent pollen type in the corbiculae in Conceição do Castelo municipality; Eucalyptus, Myrcia, and Melastomatacea/Combretaceae in the Fazenda do Estado district; and Eucalyptus and Myrcia in the São Paulo de Aracê district, both in the Domingos Martins municipality. Eucalyptus and Melastomataceae/Combretaceae were the predominant pollen types in the food pots. Eucalyptus was the most prevalent type all year round or most of the year. The most common pollen types in the months that Eucalyptus was not present or dominant in the samples were of remaining native forest species, "ruderal" (field) plants, fruit-bearing plants, and introduced ornamental plants.

The Use of Polliniferous Resources by Melipona capixaba, an Endangered Stingless Bee Species

PubMed Central

Serra, Bruna Danielle Vieira; da Luz, Cynthia Fernandes Pinto; Campos, Lucio Antonio de Oliveira

2012-01-01

Pollen types present in samples from corbiculae of Melipona capixaba (Moure and Camargo) (Hymenoptera: Apidae: Meliponina) worker bees were analyzed, as well as pollen samples from food pots inside the hives in three sites located at the bees’ original habitat. The aim was to find out the sources used as a trophic resource by this species. The dominant pollen grains in the spectrum of the samples belonged to the families Myrtaceae and Melastomataceae. Eucalyptus was the most frequent pollen type in the corbiculae in Conceição do Castelo municipality; Eucalyptus, Myrcia, and Melastomatacea/Combretaceae in the Fazenda do Estado district; and Eucalyptus and Myrcia in the São Paulo de Aracê district, both in the Domingos Martins municipality. Eucalyptus and Melastomataceae/Combretaceae were the predominant pollen types in the food pots. Eucalyptus was the most prevalent type all year round or most of the year. The most common pollen types in the months that Eucalyptus was not present or dominant in the samples were of remaining native forest species, “ruderal” (field) plants, fruit-bearing plants, and introduced ornamental plants. PMID:23464528

Novel selective human mitochondrial kinase inhibitors: design, synthesis and enzymatic activity.

PubMed

Ciliberti, Nunzia; Manfredini, Stefano; Angusti, Angela; Durini, Elisa; Solaroli, Nicola; Vertuani, Silvia; Buzzoni, Lisa; Bonache, Maria Cruz; Ben-Shalom, Efrat; Karlsson, Anna; Saada, Ann; Balzarini, Jan

2007-04-15

Selective and effective TK2 inhibitors can be obtained by introduction of bulky lipophilic chains (acyl or alkyl entities) at the 2' position of araT and BVaraU, nucleoside analogues naturally endowed with a low TK2 affinity. These derivatives showed a competitive inhibitory activity against TK2 in micromolar range. BVaraU nucleoside analogues, modified on the 2'-O-acyl chain with a terminal N-Boc amino-group, conserved or increased the inhibitory activity against TK2 (7l and 7m IC(50): 6.4 and 3.8 microM, respectively). The substitution of an ester for a carboxamide moiety at the 2' position of araT afforded a consistent reduction of the inhibitory activity (25, IC(50): 480 microM). On the contrary, modifications at 2'-OH position of araC and araG, have provided inactive derivatives against TK2 and dGK, respectively. The biological activity of a representative compound, 2'-O-decanoyl-BVaraU, was also investigated in normal human fibroblasts and was found to impair mitochondrial function due to TK2 inhibition.

Synthesis and functional evaluation of a peptide derivative of 1-beta-D-arabinofuranosylcytosine.

PubMed

Balajthy, Z; Aradi, J; Kiss, I T; Elödi, P

1992-09-04

We have synthesized a peptidyl prodrug derivative of 1-beta-D-arabinofuranosylcytosine (1) designed to be a selective substrate of plasmin. D-Val-Leu-Lys-ara-C (2) was obtained by coupling the protected peptide Cbz-D-Val-Leu-(N6-Cbz)Lys-OH and ara-C (1) by a water-soluble carbodiimide (EDCI), followed by the removal of the Cbz groups by using catalytic hydrogenolysis over Pd/C. The kinetic constant of hydrolysis of 2 in the presence of plasmin demonstrated effective release of 1. The amino group of 1, which is sensitive to the removal by cytidine deaminase, is protected in 2 by the formation of the amide bond resulting in a prolonged half-life of 2 in biological milieu. The antiproliferative efficiency of 2 against L1210 leukemic cells was significantly higher than that of 1. The activity of 2 was abolished in the presence of serine proteinase inhibitor, (4-amidinopheny)methanesulfonyl fluoride. These data indicate that 2 is a prodrug form of 1 in systems generating plasmin.

Isolated CNS relapse following stem cell transplantation for juvenile myelomonocytic leukemia.

PubMed

Wilson, David B; Michalski, Jeff M; Grossman, William J; Hayashi, Robert J

2003-11-01

A 1-year-old girl with juvenile myelomonocytic leukemia (JMML) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. A few months after BMT she experienced a bone marrow relapse that did not respond to withdrawal of immunosuppression. To enhance the graft-versus-leukemia (GVL) effect, she underwent peripheral stem cell transplantation (PSCT) from the same donor, using a nonmyeloablative conditioning regimen. She achieved clinical remission and developed chronic graft-versus-host disease (GVHD), which was treated with prednisone and cyclosporine A. One year after PSCT she experienced an isolated central nervous system (CNS) relapse. She was treated with intrathecal Ara-C followed by craniospinal irradiation and achieved a third clinical remission. While extramedullary relapses have been described in JMML, this is the first report of a CNS relapse. Based on this case and others in the literature, the authors suggest that newer therapies are changing the natural history of JMML. By manipulating the GVL effect it is possible to achieve a prolonged bone marrow remission, but only at the expense of unmasking the risk of late extramedullary relapse.

Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers.

PubMed

Sarpietro, Maria Grazia; Ottimo, Sara; Giuffrida, Maria Chiara; Rocco, Flavio; Ceruti, Maurizio; Castelli, Francesco

2011-03-15

Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is an attractive therapeutic agent for the treatment of both acute and chronic myeloblastic leukemias. 1,1',2-tris-nor-Squalene acid (squaleneCOOH) has been conjugated to cytarabine with the formation of the squalenoyl-cytarabine prodrug, in order to improve the drug lipophilicity and, consequently, the affinity towards the environment of biological membranes, as well as of lipophilic carriers. The interaction of cytarabine and its prodrug with dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles and monolayers has been studied by the differential scanning calorimetry and the Langmuir-Blodgett techniques. The interaction has been evaluated considering the effect of the compounds on the DMPC MLV and monolayers behaviour. The aim was to have information on the interaction of the drug and the prodrug with the biological membranes and on the possibility to use liposomes as carriers for the prodrug. The results showed an improved affinity of the prodrug with MLV and monolayers with respect to the free drug. Copyright © 2011 Elsevier B.V. All rights reserved.

Post-Taconic blueschist suture in the northern Appalachians of northern New Brunswick, Canada

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

van Staal, C.R.; Ravenhurst, C.E.; Roddick, J.C.

1990-11-01

A narrow belt of Late Ordovician-Early Silurian blueschist, at least 70 km long, separates an allochthonous fragment of back-arc oceanic crust of the Middle Ordovician Fournier Group from underlying, rift-related volcanic rocks of the Middle Ordovician Tetagouche Group in northern New Brunswick, Canada. The basalts on both sides of the blueschist belt are predominantly metamorphosed to greenschist facies conditions. The blueschist belt is interpreted to be an out-of-sequence thrust zone that accommodated tectonic transport of higher pressure rocks on top of lower pressure rocks during post-peak blueschist facies metamorphism. The blueschists have higher Fe{sub 2}O{sub 3}/FeO ratios and total ironmore » contents in comparison to otherwise chemically equivalent basalts of the Fournier and Tetagouche Groups that have been metamorphosed into greenschists. The blueschist belt was probably the site of channelized flow of oxidizing fluids during active deformation ina subduction complex formed during the closure of a wide Taconic back-arac basin in Late Ordovician-Silurian time.« less

Emergency Response Capability Baseline Needs Assessment - Requirements Document

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

Sharry, John A.

This document was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by LLNL Emergency Management Department Head James Colson. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only addresses emergency response.

Analysis of Capabilities of Organizations in the Areas of Responsibility for U.S. Commands of the United States Navy to Humanitarian Assistance and Disaster Relief

DTIC Science & Technology

2015-09-30

Items ..................................... 14 Table 6. Health Action...Red Cross 3436 3381 3,055 90.4 The Salvation Army International 3388 3289 2,706 82.3 Baptist Health South Florida 2637...Distribution Health Service Support Collaboration & Governance Information & Knowledge Mgt Core Competencies and Capabilities for Disaster Response

Structural reliability assessment capability in NESSUS

NASA Technical Reports Server (NTRS)

Millwater, H.; Wu, Y.-T.

1992-01-01

The principal capabilities of NESSUS (Numerical Evaluation of Stochastic Structures Under Stress), an advanced computer code developed for probabilistic structural response analysis, are reviewed, and its structural reliability assessed. The code combines flexible structural modeling tools with advanced probabilistic algorithms in order to compute probabilistic structural response and resistance, component reliability and risk, and system reliability and risk. An illustrative numerical example is presented.

Structural reliability assessment capability in NESSUS

NASA Astrophysics Data System (ADS)

Millwater, H.; Wu, Y.-T.

1992-07-01

The principal capabilities of NESSUS (Numerical Evaluation of Stochastic Structures Under Stress), an advanced computer code developed for probabilistic structural response analysis, are reviewed, and its structural reliability assessed. The code combines flexible structural modeling tools with advanced probabilistic algorithms in order to compute probabilistic structural response and resistance, component reliability and risk, and system reliability and risk. An illustrative numerical example is presented.

A Forest Fire Sensor Web Concept with UAVSAR

NASA Astrophysics Data System (ADS)

Lou, Y.; Chien, S.; Clark, D.; Doubleday, J.; Muellerschoen, R.; Zheng, Y.

2008-12-01

We developed a forest fire sensor web concept with a UAVSAR-based smart sensor and onboard automated response capability that will allow us to monitor fire progression based on coarse initial information provided by an external source. This autonomous disturbance detection and monitoring system combines the unique capabilities of imaging radar with high throughput onboard processing technology and onboard automated response capability based on specific science algorithms. In this forest fire sensor web scenario, a fire is initially located by MODIS/RapidFire or a ground-based fire observer. This information is transmitted to the UAVSAR onboard automated response system (CASPER). CASPER generates a flight plan to cover the alerted fire area and executes the flight plan. The onboard processor generates the fuel load map from raw radar data, used with wind and elevation information, predicts the likely fire progression. CASPER then autonomously alters the flight plan to track the fire progression, providing this information to the fire fighting team on the ground. We can also relay the precise fire location to other remote sensing assets with autonomous response capability such as Earth Observation-1 (EO-1)'s hyper-spectral imager to acquire the fire data.

Operationally Responsive Space Launch for Space Situational Awareness Missions

NASA Astrophysics Data System (ADS)

Freeman, T.

The United States Space Situational Awareness capability continues to be a key element in obtaining and maintaining the high ground in space. Space Situational Awareness satellites are critical enablers for integrated air, ground and sea operations, and play an essential role in fighting and winning conflicts. The United States leads the world space community in spacecraft payload systems from the component level into spacecraft and in the development of constellations of spacecraft. This position is founded upon continued government investment in research and development in space technology, which is clearly reflected in the Space Situational Awareness capabilities and the longevity of these missions. In the area of launch systems that support Space Situational Awareness, despite the recent development of small launch vehicles, the United States launch capability is dominated by unresponsive and relatively expensive launchers in the Expandable, Expendable Launch Vehicles (EELV). The EELV systems require an average of six to eight months from positioning on the launch table until liftoff. Access to space requires maintaining a robust space transportation capability, founded on a rigorous industrial and technology base. To assure access to space, the United States directed Air Force Space Command to develop the capability for operationally responsive access to space and use of space to support national security, including the ability to provide critical space capabilities in the event of a failure of launch or on-orbit capabilities. Under the Air Force Policy Directive, the Air Force will establish, organize, employ, and sustain space forces necessary to execute the mission and functions assigned including rapid response to the National Command Authorities and the conduct of military operations across the spectrum of conflict. Air Force Space Command executes the majority of spacelift operations for DoD satellites and other government and commercial agencies. The Command researched and identified a course of action that has maximized operationally responsive space for Low-Earth-Orbit Space Situational Awareness assets. On 1 Aug 06, Air Force Space Command activated the Space Development and Test Wing (SDTW) to perform development, test and evaluation of Air Force space systems and to execute advanced space deployment and demonstration projects to exploit new concepts and technologies, and rapidly migrate capabilities to the warfighter. The SDTW charged the Launch Test Squadron (LTS) to develop the operationally responsive spacelift capability for Low-Earth-Orbit Space Situational Awareness assets. The LTS created and executed a space enterprise strategy to place small payloads (1500 pounds), at low cost (less than 28M to 30M per launch), repeatable and rapidly into 100 - 255 nautical miles orbits. In doing so, the squadron provides scalable launch support services including program management support, engineering support, payload integration, and post-test evaluation for space systems. The Air Force, through the SDTW/LTS, will continue to evolve as the spacelift execution arm for Space Situational Awareness by creating small, less-expensive, repeatable and operationally responsive space launch capability.

Adaptation, Acceptance and Adaptive Preferences in Health and Capability Well-Being Measurement Amongst Those Approaching End of Life.

PubMed

Coast, Joanna; Bailey, Cara; Orlando, Rosanna; Armour, Kathy; Perry, Rachel; Jones, Louise; Kinghorn, Philip

2018-05-09

Adaptive preferences occur when people subconsciously alter their views to account for the possibilities available to them. Adaptive preferences may be problematic where these views are used in resource allocation decisions because they may lead to underestimation of the true benefits of providing services. This research explored the nature and extent of both adaptation (changing to better suit the context) and adaptive preferences (altering preferences in response to restricted options) in individuals approaching the end of life (EoL). Qualitative data from 'thinkaloud' interviews with 33 hospice patients, 22 close persons and 17 health professionals were used alongside their responses to three health/well-being measures for use in resource allocation decisions: EQ-5D-5L (health status); ICECAP-A (adult capability); and ICECAP-SCM (Supportive Care Measure; EoL capability). Constant comparative analysis combined a focus on both verbalised perceptions across the three groups and responses to the measures. Data collection took place between October 2012 and February 2014. Informants spoke clearly about how patients had adapted their lives in response to symptoms associated with their terminal condition. It was often seen as a positive choice to accept their state and adapt in this way but, at the same time, most patients were fully aware of the health and capability losses that they had faced. Self-assessments of health and capability generally appeared to reflect the pre-adaptation state, although there were exceptions. Despite adapting to their conditions, the reference group for individuals approaching EoL largely remained a healthy, capable population, and most did not show evidence of adaptive preferences.

No Emergency Incident Recognizes Borders

DTIC Science & Technology

2011-03-01

ABSTRACT (maximum 200 words) The state of Arizona and the bordering towns of northern Mexico acknowledge the need for capability planning. They...northern Mexico are taking a preventive approach and have created the Bi- National Arizona Emergency Response Task Force (BAERTF). The goal of the...BAERTF is to deliver a timely, supportive response and automatic, mutual-aid capability to any jurisdiction in the state of Arizona or northern Mexico

A Coupled Layerwise Analysis of the Thermopiezoelectric Response of Smart Composite Beams Beams

NASA Technical Reports Server (NTRS)

Lee, H.-J.; Saravanos, D. A.

1995-01-01

Thermal effects are incorporated into previously developed discrete layer mechanics for piezoelectric composite beam structures. The updated mechanics explicitly account for the complete coupled thermoelectromechanical response of smart composite beams. This unified representation leads to an inherent capability to model both the sensory and actuator responses of piezoelectric composite beams in a thermal environment. Finite element equations are developed and numerical results are presented to demonstrate the capability of the current formulation to represent the behavior of both sensory and active smart structures under thermal loadings.

Countering a bioterrorist introduction of pathogen-infected mosquitoes through mosquito control.

PubMed

Tabachnick, Walter J; Harvey, William R; Becnel, James J; Clark, Gary G; Connelly, C Roxanne; Day, Jonathan F; Linser, Paul J; Linthicum, Kenneth J

2011-06-01

The release of infected mosquitoes or other arthropods by bioterrorists, i.e., arboterrorism, to cause disease and terror is a threat to the USA. A workshop to assess mosquito control response capabilities to mount rapid and effective responses to eliminate an arboterrorism attack provided recommendations to improve capabilities in the USA. It is essential that mosquito control professionals receive training in possible responses, and it is recommended that a Council for Emergency Mosquito Control be established in each state to coordinate training, state resources, and actions for use throughout the state.

Development of a model protection and dynamic response monitoring system for the national transonic facility

NASA Technical Reports Server (NTRS)

Young, Clarence P., Jr.; Balakrishna, S.; Kilgore, W. Allen

1995-01-01

A state-of-the-art, computerized mode protection and dynamic response monitoring system has been developed for the NASA Langley Research Center National Transonic Facility (NTF). This report describes the development of the model protection and shutdown system (MPSS). A technical description of the system is given along with discussions on operation and capabilities of the system. Applications of the system to vibration problems are presented to demonstrate the system capabilities, typical applications, versatility, and investment research return derived from the system to date. The system was custom designed for the NTF but can be used at other facilities or for other dynamic measurement/diagnostic applications. Potential commercial uses of the system are described. System capability has been demonstrated for forced response testing and for characterizing and quantifying bias errors for onboard inertial model attitude measurement devices. The system is installed in the NTF control room and has been used successfully for monitoring, recording and analyzing the dynamic response of several model systems tested in the NTF.

Autonomous Soft Robotic Fish Capable of Escape Maneuvers Using Fluidic Elastomer Actuators.

PubMed

Marchese, Andrew D; Onal, Cagdas D; Rus, Daniela

2014-03-01

In this work we describe an autonomous soft-bodied robot that is both self-contained and capable of rapid, continuum-body motion. We detail the design, modeling, fabrication, and control of the soft fish, focusing on enabling the robot to perform rapid escape responses. The robot employs a compliant body with embedded actuators emulating the slender anatomical form of a fish. In addition, the robot has a novel fluidic actuation system that drives body motion and has all the subsystems of a traditional robot onboard: power, actuation, processing, and control. At the core of the fish's soft body is an array of fluidic elastomer actuators. We design the fish to emulate escape responses in addition to forward swimming because such maneuvers require rapid body accelerations and continuum-body motion. These maneuvers showcase the performance capabilities of this self-contained robot. The kinematics and controllability of the robot during simulated escape response maneuvers are analyzed and compared with studies on biological fish. We show that during escape responses, the soft-bodied robot has similar input-output relationships to those observed in biological fish. The major implication of this work is that we show soft robots can be both self-contained and capable of rapid body motion.

2D and 3D Multiscale/Multicomponent Modeling of Impact Response of Heterogeneous Energetic Composites

DTIC Science & Technology

2016-06-01

7 Development of Cohesive Finite Element Method (CFEM) Capability ................................7 3D...Cohesive Finite Element Method (CFEM) framework A new scientific framework and technical capability is developed for the computational analyses of...this section should shift from reporting activities to reporting accomplishments. Development of Cohesive Finite Element Method (CFEM) Capability

Space station operations management

NASA Technical Reports Server (NTRS)

Cannon, Kathleen V.

1989-01-01

Space Station Freedom operations management concepts must be responsive to the unique challenges presented by the permanently manned international laboratory. Space Station Freedom will be assembled over a three year period where the operational environment will change as significant capability plateaus are reached. First Element Launch, Man-Tended Capability, and Permanent Manned Capability, represent milestones in operational capability that is increasing toward mature operations capability. Operations management concepts are being developed to accomodate the varying operational capabilities during assembly, as well as the mature operational environment. This paper describes operations management concepts designed to accomodate the uniqueness of Space Station Freedoom, utilizing tools and processes that seek to control operations costs.

Request and Requirements Development Process for Operationally Responsive Space Capabilities

DTIC Science & Technology

2013-03-01

future responsive space rapid acquisition urgent need is the Space Enabled Effects for Military Engagement ( SeeMe ) program. The SeeMe concept is to...developmental time the SeeMe satellites would leverage commercial off the shelf components.39 The ORS office, working with DARPA and the commercial vender would...coordinate deployment of a SeeMe capability. It is important to note, determining the acquisition employment path focuses on availability of a

The capability of fluoroscopic systems to determine differential Roentgen-ray absorption

NASA Technical Reports Server (NTRS)

Baily, N. A.; Crepeau, R. L.

1975-01-01

A clinical fluoroscopic unit used in conjunction with a TV image digitization system was investigated to determine its capability to evaluate differential absorption between two areas in the same field. Fractional contrasts and minimum detectability for air, several concentrations of Renografin-60, and aluminum were studied using phantoms of various thicknesses. Results showed that the videometric response, when treated as contrast, shows a linear response with absorber thickness up to considerable thicknesses.

Testing the Data Assimilation Capability of the Profiler Virtual Module

DTIC Science & Technology

2016-02-01

ARL-TR-7601 ● FEB 2016 US Army Research Laboratory Testing the Data Assimilation Capability of the Profiler Virtual Module by...originator. ARL-TR-7601 ● FEB 2016 US Army Research Laboratory Testing the Data Assimilation Capability of the Profiler Virtual...hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and

Improving emergency preparedness and crisis management capabilities in transportation.

DOT National Transportation Integrated Search

2009-11-30

Despite the heightened attention disaster preparedness and emergency management have received over the past decade, serious weaknesses in the United States emergency response capabilities remain at all levels of government and across a wide range ...

The International Space Station: New Capabilities for Disaster Response and Humanitarian Aid

NASA Technical Reports Server (NTRS)

Stefanov, William

2012-01-01

The International Space Station (ISS) has been acquiring Earth imagery since 2000, primarily in the form of astronaut photography using hand-held film and digital cameras. Recent additions of more sophisticated multispectral and hyperspectral sensor systems have expanded both the capabilities and relevance of the ISS to basic research, applied Earth science, and development of new sensor technologies. Funding opportunities established within NASA, the US National Laboratories and the international partner organizations have generated instrument proposals that will further enhance these capabilities. With both internal and external sensor location options, and the availability of both automated and human-tended operational environments, the ISS is a unique platform within the constellation of Earth-observing satellites currently in orbit. Current progress and challenges associated with development of ISS terrestrial remote sensing capabilities in the area of disaster response and support of relief efforts will be presented. The ISS orbit allows for imaging of the Earth's surface at varying times of day and night, providing opportunities for data collection over approximately 95% of the populated regions. These opportunities are distinct from--yet augment--the data collection windows for the majority of sensors on polar-orbiting satellites. In addition to this potential for "being in the right place at the right time" to collect critical information on an evolving disaster, the presence of a human crew also allows for immediate recognition of an event from orbit, notification of relevant organizations on the ground, and re-tasking of available remote sensing resources to support humanitarian response and relief efforts. Challenges to establishing an integrated response capability are both technical (coordination of sensor targeting and data collection, rapid downlink and posting of data to a central accessible hub, timely generation and distribution of relevant data products) and operational (notification and engagement of sensor support teams, international partner agency sanction of astronaut support activities). To better collaborate on common issues and strengthen applications, including using the data to support disaster response, we established an ISS Program Science Forum Working Group for Earth Observations comprised of representatives from the international partner agencies. This international forum welcomes input and support from relevant United Nations task groups regarding our disaster response and humanitarian aid to enable development of the ISS capabilities in this area for greatest value to the international community.

Real-Time Simulation for Verification and Validation of Diagnostic and Prognostic Algorithms

NASA Technical Reports Server (NTRS)

Aguilar, Robet; Luu, Chuong; Santi, Louis M.; Sowers, T. Shane

2005-01-01

To verify that a health management system (HMS) performs as expected, a virtual system simulation capability, including interaction with the associated platform or vehicle, very likely will need to be developed. The rationale for developing this capability is discussed and includes the limited capability to seed faults into the actual target system due to the risk of potential damage to high value hardware. The capability envisioned would accurately reproduce the propagation of a fault or failure as observed by sensors located at strategic locations on and around the target system and would also accurately reproduce the control system and vehicle response. In this way, HMS operation can be exercised over a broad range of conditions to verify that it meets requirements for accurate, timely response to actual faults with adequate margin against false and missed detections. An overview is also presented of a real-time rocket propulsion health management system laboratory which is available for future rocket engine programs. The health management elements and approaches of this lab are directly applicable for future space systems. In this paper the various components are discussed and the general fault detection, diagnosis, isolation and the response (FDIR) concept is presented. Additionally, the complexities of V&V (Verification and Validation) for advanced algorithms and the simulation capabilities required to meet the changing state-of-the-art in HMS are discussed.

A Fast Response Capability within NOAA/NOS/CO-OPS

DTIC Science & Technology

2007-01-01

A Fast Response Capability within NOAA/NOS/CO-OPS P. B. Burke NOAA/National Ocean Service/CO-OPS 1305 East-West Hwy. Silver Spring, MD 20910...USA pat.burke@noaa.gov T. Graff NOAA/National Ocean Service/CO-OPS 1305 East-West Hwy. Silver Spring, MD 20910 USA tammy.graff@noaa.gov... flotation hull, an instrumentation tower mounted atop the hull and a current meter mount with a mooring attachment. The triangular tower housed two

Extend MANPADS M&S Capabilities to Include Energetic Materials, Fragmentation Effects, and Wing Flutter Response

DTIC Science & Technology

2005-12-31

MANPADS missile is modeled using LSDYNA . It has 187600 nodes, 52802 shell elements with 13 shell materials, 112200 solid elements with 1804 solid...model capability that includes impact, detonation, penetration, and wing flutter response. This work extends an existing body on body missile model...the missile as well as the expansion of the surrounding fluids was modeled in the Eulerian domain. The Jones-Wilkins-Lee (JWL) equation of state was

24 CFR 58.12 - Technical and administrative capacity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Technical and administrative... RESPONSIBILITIES General Policy: Responsibilities of Responsible Entities § 58.12 Technical and administrative capacity. The responsible entity must develop the technical and administrative capability necessary to...

Finite Element Analysis of Active and Sensory Thermopiezoelectric Composite Materials. Degree awarded by Northwestern Univ., Dec. 2000

NASA Technical Reports Server (NTRS)

Lee, Ho-Jun

2001-01-01

Analytical formulations are developed to account for the coupled mechanical, electrical, and thermal response of piezoelectric composite materials. The coupled response is captured at the material level through the thermopiezoelectric constitutive equations and leads to the inherent capability to model both the sensory and active responses of piezoelectric materials. A layerwise laminate theory is incorporated to provide more accurate analysis of the displacements, strains, stresses, electric fields, and thermal fields through-the-thickness. Thermal effects which arise from coefficient of thermal expansion mismatch, pyroelectric effects, and temperature dependent material properties are explicitly accounted for in the formulation. Corresponding finite element formulations are developed for piezoelectric beam, plate, and shell elements to provide a more generalized capability for the analysis of arbitrary piezoelectric composite structures. The accuracy of the current formulation is verified with comparisons from published experimental data and other analytical models. Additional numerical studies are also conducted to demonstrate additional capabilities of the formulation to represent the sensory and active behaviors. A future plan of experimental studies is provided to characterize the high temperature dynamic response of piezoelectric composite materials.

Joint Enabling Capabilities Command

Science.gov Websites

Executive Director Chief of Staff Joint Planning Support Element Joint Communications Support Element mission Joint Enabling Capabilities Command provides decisive joint communications, planning and public and responsive support for joint communications, planning and public affairs. Priorities * Deliver

Improving emergency preparedness and crisis management capabilities in transportation : year 2.

DOT National Transportation Integrated Search

2013-03-01

While disaster preparedness and emergency management have had a high public : profile over the past decade, Hurricane Katrina revealed serious weaknesses in the : United States emergency response capabilities. There is thus much left to do : befor...

48 CFR 19.602-1 - Referral.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SMALL BUSINESS PROGRAMS Certificates of Competency and Determinations of Responsibility 19.602-1... certain elements of responsibility (including, but not limited to, capability, competency, capacity...

Fine-tuning synthesis of Yersinia pestis LcrV from runaway-like replication balanced-lethal plasmid in a Salmonella enterica serovar typhimurium vaccine induces protection against a lethal Y. pestis challenge in mice.

PubMed

Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M; Branger, Christine G; Tinge, Steven A; Curtiss, Roy

2010-06-01

A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal DeltaasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain chi9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/P(cro)) (P(R)), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC P(BAD) c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of beta-lactamase, and cloned into pYA4534 under the control of the P(trc) promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain chi9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route.

Fine-Tuning Synthesis of Yersinia pestis LcrV from Runaway-Like Replication Balanced-Lethal Plasmid in a Salmonella enterica Serovar Typhimurium Vaccine Induces Protection against a Lethal Y. pestis Challenge in Mice▿

PubMed Central

Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Gunn, Bronwyn M.; Branger, Christine G.; Tinge, Steven A.; Curtiss, Roy

2010-01-01

A balanced-lethal plasmid expression system that switches from low-copy-number to runaway-like high-copy-number replication (pYA4534) was constructed for the regulated delayed in vivo synthesis of heterologous antigens by vaccine strains. This is an antibiotic resistance-free maintenance system containing the asdA gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal ΔasdA allele in live recombinant attenuated Salmonella vaccines (RASVs) such as Salmonella enterica serovar Typhimurium strain χ9447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator/promoter of the P22 cro gene (O/Pcro) (PR), which is negatively regulated by an arabinose-inducible P22 c2 gene located on both the plasmid and the chromosome (araC PBAD c2). The absence of arabinose, which is unavailable in vivo, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the Yersinia pestis virulence antigen LcrV was used to develop a vaccine against plague. An lcrV sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in Salmonella, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of β-lactamase, and cloned into pYA4534 under the control of the Ptrc promoter to generate plasmid pYA4535. Our results indicate that the live Salmonella vaccine strain χ9447 harboring pYA4535 efficiently stimulated a mixed Th1/Th2 immune response that protected mice against lethal challenge with Y. pestis strain CO92 introduced through either the intranasal or subcutaneous route. PMID:20308296

Emergency Preparedness and Response Systems

DTIC Science & Technology

2006-09-01

over time. Preparedness plans include program initiatives for planning, training, equipping, exercising, and evaluating capability to ensure sustainable ... performance in order to prevent, prepare for and respond to incidents. 4. Response Response refers to the activities necessary to address the

The corporate social responsibility of the pharmaceutical industry: idealism without illusion and realism without resignation.

PubMed

Leisinger, Klaus M

2005-10-01

In recent years society has come to expect more from the "socially-responsible" company and the global HIV/AIDS pandemic in particular has resulted in some critics saying that the "Big Pharma" companies have not been living up to their social responsibilities. Corporate social responsibility can be understood as the socio-economic product of the organizational division of labor in complex modern society. Global poverty and poor health conditions are in the main the responsibilities of the world's national governments and international governmental organizations, which possess society's mandate and appropriate organizational capabilities. Private enterprises have neither the societal mandate nor the organizational capabilities to feed the poor or provide health care to the sick in their home countries or in the developing world. Nevertheless, private enterprises do have responsibilities to society that can be categorized as what they must do, what they ought do, and what they can do.

INCA- INTERACTIVE CONTROLS ANALYSIS

NASA Technical Reports Server (NTRS)

Bauer, F. H.

1994-01-01

The Interactive Controls Analysis (INCA) program was developed to provide a user friendly environment for the design and analysis of linear control systems, primarily feedback control systems. INCA is designed for use with both small and large order systems. Using the interactive graphics capability, the INCA user can quickly plot a root locus, frequency response, or time response of either a continuous time system or a sampled data system. The system configuration and parameters can be easily changed, allowing the INCA user to design compensation networks and perform sensitivity analysis in a very convenient manner. A journal file capability is included. This stores an entire sequence of commands, generated during an INCA session into a file which can be accessed later. Also included in INCA are a context-sensitive help library, a screen editor, and plot windows. INCA is robust to VAX-specific overflow problems. The transfer function is the basic unit of INCA. Transfer functions are automatically saved and are available to the INCA user at any time. A powerful, user friendly transfer function manipulation and editing capability is built into the INCA program. The user can do all transfer function manipulations and plotting without leaving INCA, although provisions are made to input transfer functions from data files. By using a small set of commands, the user may compute and edit transfer functions, and then examine these functions by using the ROOT_LOCUS, FREQUENCY_RESPONSE, and TIME_RESPONSE capabilities. Basic input data, including gains, are handled as single-input single-output transfer functions. These functions can be developed using the function editor or by using FORTRAN- like arithmetic expressions. In addition to the arithmetic functions, special functions are available to 1) compute step, ramp, and sinusoid functions, 2) compute closed loop transfer functions, 3) convert from S plane to Z plane with optional advanced Z transform, and 4) convert from Z plane to W plane and back. These capabilities allow the INCA user to perform block diagram algebraic manipulations quickly for functions in the S, Z, and W domains. Additionally, a versatile digital control capability has been included in INCA. Special plane transformations allow the user to easily convert functions from one domain to another. Other digital control capabilities include: 1) totally independent open loop frequency response analyses on a continuous plant, discrete control system with a delay, 2) advanced Z-transform capability for systems with delays, and 3) multirate sampling analyses. The current version of INCA includes Dynamic Functions (which change when a parameter changes), standard filter generation, PD and PID controller generation, incorporation of the QZ-algorithm (function addition, inverse Laplace), and describing functions that allow the user to calculate the gain and phase characteristics of a nonlinear device. The INCA graphic modes provide the user with a convenient means to document and study frequency response, time response, and root locus analyses. General graphics features include: 1) zooming and dezooming, 2) plot documentation, 3) a table of analytic computation results, 4) multiple curves on the same plot, and 5) displaying frequency and gain information for a specific point on a curve. Additional capabilities in the frequency response mode include: 1) a full complement of graphical methods Bode magnitude, Bode phase, Bode combined magnitude and phase, Bode strip plots, root contour plots, Nyquist, Nichols, and Popov plots; 2) user selected plot scaling; and 3) gain and phase margin calculation and display. In the time response mode, additional capabilities include: 1) support for inverse Laplace and inverse Z transforms, 2) support for various input functions, 3) closed loop response evaluation, 4) loop gain sensitivity analyses, 5) intersample time response for discrete systems using the advanced Z transform, and 6) closed loop time response using mixed plane (S, Z, W) operations with delay. A Graphics mode command was added to the current version of INCA, version 3.13, to produce Metafiles (graphic files) of the currently displayed plot. The metafile can be displayed and edited using the QPLOT Graphics Editor and Replotter for Metafiles (GERM) program included with the INCA package. The INCA program is written in Pascal and FORTRAN for interactive or batch execution and has been implemented on a DEC VAX series computer under VMS. Both source code and executable code are supplied for INCA. Full INCA graphics capabilities are supported for various Tektronix 40xx and 41xx terminals; DEC VT graphics terminals; many PC and Macintosh terminal emulators; TEK014 hardcopy devices such as the LN03 Laserprinter; and bit map graphics external hardcopy devices. Also included for the TEK4510 rasterizer users are a multiple copy feature, a wide line feature, and additional graphics fonts. The INCA program was developed in 1985, Version 2.04 was released in 1986, Version 3.00 was released in 1988, and Version 3.13 was released in 1989. An INCA version 2.0X conversion program is included.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

PubMed

Milano, G; Thyss, A; Serre Debeauvais, F; Laureys, G; Benoit, Y; Deville, A; Dutour, C; Robert, A; Otten, J; Behar, C

1990-04-01

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Synthesis and evaluation of macromolecule-bound derivatives of a peptidyl-1-beta-D-arabinofuranosylcytosine prodrug.

PubMed

Balajthy, Zoltan

2008-04-01

Macromolecule-bound Val-Leu-Lys-ara-C (1) prodrugs were synthesized with spacers (-HN-(CH(2))(x)-CO-; x =1,3,5) between the dextran carrier (T-70) and 1, in order to achieve a sustained-release drug delivery system dextran-NH-(CH(2))(x:1,3,5)-CO-Val-Leu-Lys-ara-C (5, 6 and 7). The conjugation increased the stability of 1 in aqueous buffer solutions by three times (t((1/2)) 53.0 h, pH 7.4). The length of spacer also regulated the rate of hydrolysis of the prodrugs in serum. The shortest spacer (-HN-(CH(2))-CO-, (2)) in 5 provided the best protection of 1 against the hydrolyzing ability of proteinase- alpha(2)-macroglobulin complexes, increasing its half-life approximately 30-fold. The conjugation procedure resulted in a growth arrest ability for macromolecular-bound prodrugs 5, 6 and 7 against L1210 with IC(50) of 0.01 microM in vitro, which is significantly lower than that of other ara-C-macromolecule conjugates. 5 and 6 arrested cell growth in a broader range of concentration, between 1 x 10(-5)-1.0 microM, than ara-C could.

Discovering the Regulatory Considerations of the Federal Aviation Administration: Interviewing the Aviation Rulemaking Advisory Committee

NASA Technical Reports Server (NTRS)

Lu, Chien-tsung

2005-01-01

Maintenance Resource Management (MRM) training for aviation mechanics has become mandatory in many industrialized countries since 1998. Yet, to date, MRM training remains optional in the U.S. Interestingly, a similar safety discipline, namely Crew/Cockpit Resource Management (CRM), is mandatory for pilots, flight engineers, flight attendants, and dispatchers and is regulated in the Federal Aviation Administration s (FAA) Federal Aviation Regulations (FARs). If MRM training is important to enhance aviation technicians working behavior, the rationale to not regulate it opens a window for study. This research aims to inductively investigate the FAA s regulatory rationale concerning MRM training based on direct inputs from the FAA s Aviation Rulemaking Advisory Committee (ARAC) members. Delphi methodology associated with purposive sampling technique was adopted. The result revealed that the FAA cannot regulate MRM because the aviation industry is strongly opposed to it due to the lack of training budgets, the need of a quantifiable cost-effect analysis, concern over the FAA s inspection workforce, an ongoing voluntary alternative called the Air Transportation Surveillance System (ATOS), the government s lower priority on maintenance after 9/11, and the airlines tight embracement of operational flexibility without regulation.

Low Cost Sensors-Current Capabilities and Gaps

EPA Science Inventory

1. Present the findings from the a recent technology review of gas and particulate phase sensors 2. Focus on the lower-cost sensors 3. Discuss current capabilities, estimated range of measurement, selectivity, deployment platforms, response time, and expected range of acceptabl...

Layerwise Finite Elements for Smart Piezoceramic Composite Plates in Thermal Environments

NASA Technical Reports Server (NTRS)

Saravanos, Dimitris A.; Lee, Ho-Jun

1996-01-01

Analytical formulations are presented which account for the coupled mechanical, electrical, and thermal response of piezoelectric composite laminates and plate structures. A layerwise theory is formulated with the inherent capability to explicitly model the active and sensory response of piezoelectric composite plates having arbitrary laminate configurations in thermal environments. Finite element equations are derived and implemented for a bilinear 4-noded plate element. Application cases demonstrate the capability to manage thermally induced bending and twisting deformations in symmetric and antisymmetric composite plates with piezoelectric actuators, and show the corresponding electrical response of distributed piezoelectric sensors. Finally, the resultant stresses in the thermal piezoelectric composite laminates are investigated.

Emergency Response and Management Activities

EPA Pesticide Factsheets

This quarterly report, highlighting accomplishments over the past several months, showcases EPA’s unique emergency response capabilities through the use of cutting-edge technologies and innovative cleanup strategies.

Aviation System Analysis Capability Quick Response System Report

NASA Technical Reports Server (NTRS)

Roberts, Eileen; Villani, James A.; Ritter, Paul

1998-01-01

The purpose of this document is to present the additions and modifications made to the Aviation System Analysis Capability (ASAC) Quick Response System (QRS) in FY 1997 in support of the ASAC ORS development effort. This document contains an overview of the project background and scope and defines the QRS. The document also presents an overview of the Logistics Management Institute (LMI) facility that supports the QRS, and it includes a summary of the planned additions to the QRS in FY 1998. The document has five appendices.

10 CFR 50.47 - Emergency plans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... responsibilities for emergency response by the nuclear facility licensee and by State and local organizations... supporting organizations have been specifically established, and each principal response organization has... licensee's near-site Emergency Operations Facility have been made, and other organizations capable of...

How Health Department Contextual Factors Affect Public Health Preparedness (PHP) and Perceptions of the 15 PHP Capabilities

PubMed Central

Carbone, Eric G.; Lynch, Molly; Wang, Z. Joan; Jones, Terrance; Rose, Dale A.

2017-01-01

Objectives. To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. Methods. We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC’s Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. Results. Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. Conclusions. Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses. PMID:28892447

How Health Department Contextual Factors Affect Public Health Preparedness (PHP) and Perceptions of the 15 PHP Capabilities.

PubMed

Horney, Jennifer A; Carbone, Eric G; Lynch, Molly; Wang, Z Joan; Jones, Terrance; Rose, Dale A

2017-09-01

To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC's Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses.

Comprehension and engagement in survey interviews with virtual agents

PubMed Central

Conrad, Frederick G.; Schober, Michael F.; Jans, Matt; Orlowski, Rachel A.; Nielsen, Daniel; Levenstein, Rachel

2015-01-01

This study investigates how an onscreen virtual agent's dialog capability and facial animation affect survey respondents' comprehension and engagement in “face-to-face” interviews, using questions from US government surveys whose results have far-reaching impact on national policies. In the study, 73 laboratory participants were randomly assigned to respond in one of four interviewing conditions, in which the virtual agent had either high or low dialog capability (implemented through Wizard of Oz) and high or low facial animation, based on motion capture from a human interviewer. Respondents, whose faces were visible to the Wizard (and videorecorded) during the interviews, answered 12 questions about housing, employment, and purchases on the basis of fictional scenarios designed to allow measurement of comprehension accuracy, defined as the fit between responses and US government definitions. Respondents answered more accurately with the high-dialog-capability agents, requesting clarification more often particularly for ambiguous scenarios; and they generally treated the high-dialog-capability interviewers more socially, looking at the interviewer more and judging high-dialog-capability agents as more personal and less distant. Greater interviewer facial animation did not affect response accuracy, but it led to more displays of engagement—acknowledgments (verbal and visual) and smiles—and to the virtual interviewer's being rated as less natural. The pattern of results suggests that a virtual agent's dialog capability and facial animation differently affect survey respondents' experience of interviews, behavioral displays, and comprehension, and thus the accuracy of their responses. The pattern of results also suggests design considerations for building survey interviewing agents, which may differ depending on the kinds of survey questions (sensitive or not) that are asked. PMID:26539138

Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfection capability.

PubMed

Huang, Yajun; Ding, Xiaokang; Qi, Yu; Yu, Bingran; Xu, Fu-Jian

2016-11-01

There is an increasing demand in developing of multifunctional materials with good antibacterial activity, biocompatibility and drug/gene delivery capability for next-generation biomedical applications. To achieve this purpose, in this work series of hydroxyl-rich hyperbranched polyaminoglycosides of gentamicin, tobramycin, and neomycin (HP and SS-HP with redox-responsive disulfide bonds) were readily synthesized via ring-opening reactions in a one-pot manner. Both HP and SS-HP exhibit high antibacterial activity toward Escherichia coli and Staphylococcus aureus. Meanwhile, the hemolysis assay of the above materials shows good biocompatibility. Moreover, SS-HPs show excellent gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. For an in vivo anti-tumor assay, the SS-HP/p53 complexes exhibit potent inhibition capability to the growth of tumors. This study provides a promising approach for the design of next-generation multifunctional biomedical materials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Organic Scintillator Detector Response Simulations with DRiFT

DOE PAGES

Andrews, Madison Theresa; Bates, Cameron Russell; Mckigney, Edward Allen; ...

2016-06-11

Here, this work presents the organic scintillation simulation capabilities of DRiFT, a post-processing Detector Response Function Toolkit for MCNPR output. DRiFT is used to create realistic scintillation detector response functions to incident neutron and gamma mixed- field radiation. As a post-processing tool, DRiFT leverages the extensively validated radiation transport capabilities of MCNPR ®6, which also provides the ability to simulate complex sources and geometries. DRiFT is designed to be flexible, it allows the user to specify scintillator material, PMT type, applied PMT voltage, and quenching data used in simulations. The toolkit's capabilities, which include the generation of pulse shape discriminationmore » plots and full-energy detector spectra, are demonstrated in a comparison of measured and simulated neutron contributions from 252Cf and PuBe, and photon spectra from 22Na and 228Th sources. DRiFT reproduced energy resolution effects observed in EJ-301 measurements through the inclusion of scintillation yield variances, photon transport noise, and PMT photocathode and multiplication noise.« less

Organic scintillator detector response simulations with DRiFT

NASA Astrophysics Data System (ADS)

Andrews, M. T.; Bates, C. R.; McKigney, E. A.; Solomon, C. J.; Sood, A.

2016-09-01

This work presents the organic scintillation simulation capabilities of DRiFT, a post-processing Detector Response Function Toolkit for MCNP® output. DRiFT is used to create realistic scintillation detector response functions to incident neutron and gamma mixed-field radiation. As a post-processing tool, DRiFT leverages the extensively validated radiation transport capabilities of MCNP® 6 , which also provides the ability to simulate complex sources and geometries. DRiFT is designed to be flexible, it allows the user to specify scintillator material, PMT type, applied PMT voltage, and quenching data used in simulations. The toolkit's capabilities, which include the generation of pulse shape discrimination plots and full-energy detector spectra, are demonstrated in a comparison of measured and simulated neutron contributions from 252Cf and PuBe, and photon spectra from 22Na and 228Th sources. DRiFT reproduced energy resolution effects observed in EJ-301 measurements through the inclusion of scintillation yield variances, photon transport noise, and PMT photocathode and multiplication noise.

Energy Storage Opportunities and Capabilities in a Type 3 Wind Turbine Generator: Preprint

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

Muljadi, Eduard; Gevorgian, Vahan; Hoke, Andy

Wind power plants and other renewable power plants with power electronic interfaces are capable of delivering frequency response (both governor and/or inertial response) to the grid by a control action; thus, the reduction of available online inertia as conventional power plants are retired can be compensated by designing renewable power plant controls to include frequency response. The source of energy to be delivered as inertial response is determined by the type of generation and control strategy chosen. The cost of energy storage is expected to drop over time, and global research activities on energy storage are very active, funded bothmore » by the private industry and governments. Different industry sectors (e.g., transportation, energy) are the major drivers of the recent storage research and development. This work investigates the opportunities and capabilities of deploying energy storage in renewable power plants. In particular, we focus on wind power plants with doubly-fed induction generators, or Type 3 wind turbine generator (WTGs). We find that the total output power of a system with Type 3 WTGs with energy storage can deliver a power boost during inertial response that is up to 45% higher than one without energy storage without affecting the torque limit, thus enabling an effective delivery of ancillary services to the grid.« less

Operationalising the capability approach as an outcome measure in public health: The development of the OCAP-18.

PubMed

Lorgelly, Paula K; Lorimer, Karen; Fenwick, Elisabeth A L; Briggs, Andrew H; Anand, Paul

2015-10-01

There is growing interest in operationalising the capability approach to measure quality of life. This paper reports the results of a research project undertaken in 2007 that sought to reduce and refine a longer survey in order to provide a summary measure of wellbeing and capability in the realm of public health. The reduction and refinement of the questionnaire took place across a number of stages, using both qualitative (five focus group discussions and 17 in-depth interviews) and quantitative (secondary data analysis, N = 1048 and primary data collection using postal surveys and interviews, N = 45) approaches. The questionnaire was reduced from its original 60+ questions to 24 questions (including demographic questions). Each of Nussbaum's ten Central Human Capabilities are measured using one (or more) of the 18 specific capability items which are included in the questionnaire (referred to as the OCAP-18). Analysis of the questionnaire responses (N = 198) found that respondents differed with respect to the levels of capabilities they reported, and that these capabilities appear to be sensitive to one's gender, age, income and deprivation decile. An index of capability, estimated by assuming equal weight for each capability question, found that the average level of capability amongst respondents was 12.44 (range 3-17.75). This index was found to be highly correlated with a measure of health (EQ-5D) and wellbeing (global QoL), although some differences were apparent. This project operationalised the capability approach to produce an instrument to measure the effectiveness (and cost effectiveness) of public health interventions; the resulting OCAP-18 appears to be responsive and measure something supplementary to health and wellbeing, thus offers a promising addition to the current suite of outcome measures that are available. Copyright © 2015 Elsevier Ltd. All rights reserved.

Environmental Response Team

EPA Pesticide Factsheets

This website will serve as a resource directory of the Environmental Response Team's roles and capabilities as well as list contacts for each discipline to provide information to EPA personnel and the public.

Options for the Navy’s Future Fleet

DTIC Science & Technology

2006-05-01

capability than most of those options by other than for inflation, how big and how capable can the most measures of capability. But even under the Navy’s...The most prominent of those vessels are fast combat support ships, which operate with carrier strike groups to resupply them with fuel, dry Supply...categories of ships-submarines and large surface Similarly, the ship construction schedule for large surface combatants-are responsible for most of the

Alternatives to Contingency Response Group Organization: Tradeoffs to Balance Capability and Capacity

DTIC Science & Technology

2014-06-13

mobility liaison officers ( AMLOs ) aligned under them that have the mission of providing mobility expertise to Army and Marine Corps brigade and...division level commander. This paper will not address changes to the MSAS or AMLO organization, capability or capacity. Instead, this paper will examine...in the areas of enroute support, ABO, BPC, Air Mobility Division augmentation and AMLO capability (Joint Chiefs of Staff, 2013). In addition to four

Building a Capabilities Network to Improve Disaster Preparation Effort in the Pacific Command Area of Responsibility

DTIC Science & Technology

2013-06-01

efforts, identification of the organizations that are available and the capabilities that they can provide is essential. This research identifies and...military. We also analyzed the financial status of the NGOs for a better understanding. The end result of the research is to provide PACOM...are available and the capabilities that they can provide is essential. This research identifies and analyzes 27 nongovernmental organizations (NGOs

Afghan National Engineer Brigade: Despite U.S. Training Efforts, the Brigade is Incapable of Operating Independently

DTIC Science & Technology

2016-01-01

carpentry, masonry , and the operation of heavy equipment. Plans called for the NEB to receive at least $29 million in engineering equipment and...JTF Sapper, NMCB 25, and NMCB 28, had responsibility for training the NEB in such areas as plumbing, electrical work, carpentry, masonry , and...measurement tool consisted of five possible ratings: fully capable, capable, partially capable, developing, and established. USFOR-A used these

Countering Putins Nuclear-Backed Aggression with a Continuous Nuclear-Capable Bomber Presence

DTIC Science & Technology

2016-05-13

backed aggression can only be answered by a visible increase in nuclear capability in Europe. A nuclear-capable bomber force that permanently rotates ...permanently rotates through the EUCOM Area of Responsibility (AOR) would provide the United States with the ability to attack Putin’s strategy in three ways...One nuclear detonation in Europe would change the world. A BMD system cannot promise countries that it will negate every Russian nuclear missile

Coupled electromechanical response of composite beams with embedded piezoelectric sensors and actuators

NASA Technical Reports Server (NTRS)

Saravanos, D. A.; Heyliger, P. R.

1994-01-01

Unified mechanics are developed with the capability to model both sensory and active composite laminates with embedded piezoelectric layers. A discrete-layer formulation enables analysis of both global and local electromechanical response. The mechanics include the contributions from elastic, piezoelectric, and dielectric components. The incorporation of electric potential into the state variables permits representation of general electromechanical boundary conditions. Approximate finite element solutions for the static and free-vibration analysis of beams are presented. Applications on composite beams demonstrate the capability to represent either sensory or active structures and to model the complicated stress-strain fields, the interactions between passive/active layers, interfacial phenomena between sensors and composite plies, and critical damage modes in the material. The capability to predict the dynamic characteristics under various electrical boundary conditions is also demonstrated.

Flexible and wearable 3D graphene sensor with 141 KHz frequency signal response capability

NASA Astrophysics Data System (ADS)

Xu, R.; Zhang, H.; Cai, Y.; Ruan, J.; Qu, K.; Liu, E.; Ni, X.; Lu, M.; Dong, X.

2017-09-01

We developed a flexible force sensor consisting of 3D graphene foam (GF) encapsulated in flexible polydimethylsiloxane (PDMS). Because the 3D GF/PDMS sensor is based on the transformation of an electronic band structure aroused by static mechanical strain or KHz vibration, it can detect frequency signals by both tuning fork tests and piezoelectric ceramic transducer tests, which showed a clear linear response from audio frequencies, including frequencies up to 141 KHz in the ultrasound range. Because of their excellent response with a wide bandwidth, the 3D GF/PDMS sensors are attractive for interactive wearable devices or artificial prosthetics capable of perceiving seismic waves, ultrasonic waves, shock waves, and transient pressures.

10 CFR 73.45 - Performance capabilities for fixed site physical protection systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... authorization schedules and entry criteria before permitting entry and to initiate response measures to deny... movement of strategic special nuclear material within material access areas. To achieve this capability the physical protection system shall: (1) Detect unauthorized placement and movement of strategic special...

76 FR 4348 - Labor-Management Cooperation Grant Program Information Collection Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

...: Application for Federal Assistance (SF-424), Accounting System and Financial Capability Questionnaire (LM-3... the estimated time per response is 60 minutes. The Accounting System and Financial Capability... the information were not collected, there could be no accounting for the activities of the program...

Reducing Mission Costs by Leveraging Previous Investments in Space

NASA Technical Reports Server (NTRS)

Miller, Ron; Adams, W. James

1999-01-01

The Rapid Spacecraft Development Office (RSDO) at NASA's Goddard Space Flight Center has been charged with the responsibility to reduce mission cost by allowing access to previous developments on government and commercial space missions. RSDO accomplishes this responsibility by implementing two revolutionary contract vehicles, the Rapid Spacecraft Acquisition (RSA) and Quick Ride. This paper will describe the concept behind these contracts, the current capabilities available to missions, analysis of pricing trends to date using the RSDO processes, and future plans to increase flexibility and capabilities available to mission planners.

Restriction of the anti-bovine serum albumin response in rabbits immunized with Micrococcus lysodeikticus.

PubMed Central

De Baetselier, P; Hamers-Casterman, C; Van der Loo, W; Hamers, R

1977-01-01

Rabbits capable of producing antibodies of restricted heterogeneity in response to Micrococcus lysodeikticus are equally capable of producing antibodies of restricted heterogeneity to bovine serum albumin. These antibodies are produced when animals are simultaneously injected with micrococcus and BSA and their specificity is restricted to a small number of epitopes. These results suggest that micrococcal vaccines can induce the restriction of heterogeneity in antibodies raised against totally unrelated antigens. Images Figure 4 Figure 5 Figure 2 Figure 6 Figure 7 Figure 8 PMID:71263

Analyzing Response Times in Tests with Rank Correlation Approaches

ERIC Educational Resources Information Center

Ranger, Jochen; Kuhn, Jorg-Tobias

2013-01-01

It is common practice to log-transform response times before analyzing them with standard factor analytical methods. However, sometimes the log-transformation is not capable of linearizing the relation between the response times and the latent traits. Therefore, a more general approach to response time analysis is proposed in the current…

Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy.

PubMed

Xu, Lizhi; Gutbrod, Sarah R; Ma, Yinji; Petrossians, Artin; Liu, Yuhao; Webb, R Chad; Fan, Jonathan A; Yang, Zijian; Xu, Renxiao; Whalen, John J; Weiland, James D; Huang, Yonggang; Efimov, Igor R; Rogers, John A

2015-03-11

Advanced materials and fractal design concepts form the basis of a 3D conformal electronic platform with unique capabilities in cardiac electrotherapies. Fractal geometries, advanced electrode materials, and thin, elastomeric membranes yield a class of device capable of integration with the entire 3D surface of the heart, with unique operational capabilities in low power defibrillation. Co-integrated collections of sensors allow simultaneous monitoring of physiological responses. Animal experiments on Langendorff-perfused rabbit hearts demonstrate the key features of these systems. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spinning Reserve From Hotel Load Response: Initial Progress

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

Kueck, John D; Kirby, Brendan J

2008-11-01

This project was motivated by the fundamental match between hotel space conditioning load response capability and power system contingency response needs. As power system costs rise and capacity is strained demand response can provide a significant system reliability benefit at a potentially attractive cost. At ORNL s suggestion, Digital Solutions Inc. adapted its hotel air conditioning control technology to supply power system spinning reserve. This energy saving technology is primarily designed to provide the hotel operator with the ability to control individual room temperature set-points based upon occupancy (25% to 50% energy savings based on an earlier study [Kirby andmore » Ally, 2002]). DSI added instantaneous local load shedding capability in response to power system frequency and centrally dispatched load shedding capability in response to power system operator command. The 162 room Music Road Hotel in Pigeon Forge Tennessee agreed to host the spinning reserve test. The Tennessee Valley Authority supplied real-time metering equipment in the form of an internet connected Dranetz-BMI power quality meter and monitoring expertise to record total hotel load during both normal operations and test results. The Sevier County Electric System installed the metering. Preliminary testing showed that hotel load can be curtailed by 22% to 37% depending on the outdoor temperature and the time of day. These results are prior to implementing control over the common area air conditioning loads. Testing was also not at times of highest system or hotel loading. Full response occurred in 12 to 60 seconds from when the system operator s command to shed load was issued. The load drop was very rapid, essentially as fast as the 2 second metering could detect, with all units responding essentially simultaneously. Load restoration was ramped back in over several minutes. The restoration ramp can be adjusted to the power system needs. Frequency response testing was not completed. Initial testing showed that the units respond very quickly. Problems with local power quality generated false low frequency signals which required testing to be stopped. This should not be a problem in actual operation since the frequency trip points will be staggered to generate a droop curve which mimics generator governor response. The actual trip frequencies will also be low enough to avoid power quality problems. The actual trip frequencies are too low to generate test events with sufficient regularity to complete testing in a reasonable amount of time. Frequency response testing will resume once the local power quality problem is fully understood and reasonable test frequency settings can be determined. Overall the preliminary testing was extremely successful. The hotel response capability matches the power system reliability need, being faster than generation response and inherently available when the power system is under the most stress (times of high system and hotel load). Periodic testing is scheduled throughout the winter and spring to characterize hotel response capability under a full range of conditions. More extensive testing will resume when summer outdoor temperatures are again high enough to fully test hotel response.« less

12 CFR 704.4 - Board responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requirements. The board of directors of a corporate credit union must ensure: (1) Senior managers have an in-depth, working knowledge of their direct areas of responsibility and are capable of identifying, hiring...

Sucrose Responsiveness, Learning Success, and Task Specialization in Ants

ERIC Educational Resources Information Center

Perez, Margot; Rolland, Uther; Giurfa,, Martin; d'Ettorre, Patrizia

2013-01-01

Social insects possess remarkable learning capabilities, which are crucial for their ecological success. They also exhibit interindividual differences in responsiveness to environmental stimuli, which underlie task specialization and division of labor. Here we investigated for the first time the relationships between sucrose responsiveness,…

A Comprehensive Evaluation System for Military Hospitals' Response Capability to Bio-terrorism.

PubMed

Wang, Hui; Jiang, Nan; Shao, Sicong; Zheng, Tao; Sun, Jianzhong

2015-05-01

The objective of this study is to establish a comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Literature research and Delphi method were utilized to establish the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Questionnaires were designed and used to survey the status quo of 134 military hospitals' response capability to bio-terrorism. Survey indicated that factor analysis method was suitable to for analyzing the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. The constructed evaluation system was consisted of five first-class and 16 second-class indexes. Among them, medical response factor was considered as the most important factor with weight coefficient of 0.660, followed in turn by the emergency management factor with weight coefficient of 0.109, emergency management consciousness factor with weight coefficient of 0.093, hardware support factor with weight coefficient of 0.078, and improvement factor with weight coefficient of 0.059. The constructed comprehensive assessment model and system are scientific and practical.

Scaffolding and Integrated Assessment in Computer Assisted Learning (CAL) for Children with Learning Disabilities

ERIC Educational Resources Information Center

Beale, Ivan L.

2005-01-01

Computer assisted learning (CAL) can involve a computerised intelligent learning environment, defined as an environment capable of automatically, dynamically and continuously adapting to the learning context. One aspect of this adaptive capability involves automatic adjustment of instructional procedures in response to each learner's performance,…

Business Undergraduates' Perceptions of Their Capabilities in Employability Skills: Implications for Industry and Higher Education

ERIC Educational Resources Information Center

Jackson, Denise

2012-01-01

In response to the continuing disparity between industry expectations and higher education provision, this study examines the self-assessed capabilities of 1,024 business undergraduates in employability skills typically considered important by industry in developed economies. The findings indicate relative perceived strengths in "social…

Executive Development: Meeting the Needs of Top Teams and Boards.

ERIC Educational Resources Information Center

Jackson, Sheila; Farndale, Elaine; Kakabadse, Andrew

2003-01-01

A literature review and six case studies examined the roles and responsibilities of the chief executive officers and board chairs, the capabilities required for success, and related executive development activity. Findings include the importance of focusing executive development on capability enhancement to ensure that it supports organizational…

Exploring leadership capability and emotional intelligence as moderators of workplace bullying.

PubMed

Hutchinson, Marie; Hurley, John

2013-04-01

This study aimed to explore the potential for emotionally intelligent leadership as a way to mitigate bullying behaviour within nursing workplace environments. As the body of evidence about bullying continues to grow there is an increasing need for researchers to direct their attention to developing theoretical frameworks that explain how bullying and victimization occur, and the types of strategies that may address the problem. The narrative synthesis of the literature presented in this paper is forwarded as supporting the need for strengthening leadership capability, especially those capabilities associated with emotional intelligence, as a means of diminishing experienced bullying within nursing. Stemming from our expanding understandings about bullying is an appreciation of the range of factors within organizations that influence the occurrence of bullying, and an awareness of the need to understand the expression, experience and management of emotions in the workplace. While both leadership and emotional intelligence capabilities offer real potential to mitigate bullying behaviour, disparity exits between clinical and managerial nurses toward preferred leadership styles and emotional intelligence is open to challenges towards its content validity. Nursing management is challenged to build upon procedural responses to bullying to include a ground up approach to leadership enhancement capability, better responses to emotions in the workplace and supporting the interpersonal and intrapersonal capabilities of the nursing workforce. © 2012 Blackwell Publishing Ltd.

Environmental Response Laboratory Network

EPA Pesticide Factsheets

The ERLN as a national network of laboratories that can be ramped up as needed to support large scale environmental responses. It integrates capabilities of existing public and private sector labs, providing consistent capacity and quality data.

EPA’s Role in Emergency Response

EPA Pesticide Factsheets

EPA provides support when requested, or when state and local first responder capabilities have been exceeded, in response to chemical, oil, biological, and radiological releases and large-scale national emergencies, including homeland security incidents.

Preparing for catastrophe : a new U.S. framework for international disaster response.

DOT National Transportation Integrated Search

2001-06-01

The paper first makes a case for the strategic importance of U.S. disaster response capabilities in order to justify the commitment of attention and resources needed to develop a new response framework. It next reviews the current U.S. Government int...

Excited-state absorption in tetrapyridyl porphyrins: comparing real-time and quadratic-response time-dependent density functional theory

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

Bowman, David N.; Asher, Jason C.; Fischer, Sean A.

2017-01-01

Threemeso-substituted tetrapyridyl porphyrins (free base, Ni(ii), and Cu(ii)) were investigated for their optical limiting (OL) capabilities using real-time (RT-), linear-response (LR-), and quadratic-response (QR-) time-dependent density functional theory (TDDFT) methods.

Integrating a framework for conducting public health systems research into statewide operations-based exercises to improve emergency preparedness

PubMed Central

2012-01-01

Background Due to the uncommon nature of large-scale disasters and emergencies, public health practitioners often turn to simulated emergencies, known as “exercises”, for preparedness assessment and improvement. Under the right conditions, exercises can also be used to conduct original public health systems research. This paper describes the integration of a research framework into a statewide operations-based exercise program in California as a systems-based approach for studying public health emergency preparedness and response. Methods We developed a research framework based on the premise that operations-based exercises conducted by medical and public health agencies can be described using epidemiologic concepts. Using this framework, we conducted a survey of key local and regional medical and health agencies throughout California following the 2010 Statewide Medical and Health Exercise. The survey evaluated: (1) the emergency preparedness capabilities activated and functions performed in response to the emergency scenario, and (2) the major challenges to inter-organizational communications and information management. Results Thirty-five local health departments (LHDs), 24 local emergency medical services (EMS) agencies, 121 hospitals, and 5 Regional Disaster Medical and Health Coordinators/Specialists (RDMHC) responded to our survey, representing 57%, 77%, 26% and 83%, respectively, of target agencies in California. We found two sets of response capabilities were activated during the 2010 Statewide Exercise: a set of core capabilities that were common across all agencies, and a set of agency-specific capabilities that were more common among certain agency types. With respect to one response capability in particular, inter-organizational information sharing, we found that the majority of respondents’ comments were related to the complete or partial failure of communications equipment or systems. Conclusions Using the 2010 Statewide Exercise in California as an opportunity to develop our research framework, we characterized several aspects of the public health and medical system’s response to a standardized emergency scenario. From a research perspective, this study provides a potential new framework for conducting exercise-based research. From a practitioner’s perspective, our results provide a starting point for preparedness professionals’ dialogue about expected and actual organizational roles, responsibilities, and resource capacities within the public health system. Additionally, the identification of specific challenges to inter-organizational communications and information management offer specific areas for intervention. PMID:22905991

State-level emergency preparedness and response capabilities.

PubMed

Watkins, Sharon M; Perrotta, Dennis M; Stanbury, Martha; Heumann, Michael; Anderson, Henry; Simms, Erin; Huang, Monica

2011-03-01

Prior assessments of public health readiness had identified gaps in radiation preparedness. In recent years, preparedness planning has involved an "all-hazards" approach. Current assessment of the national status related to radiation public health emergency preparedness capabilities at the state and local health department levels was needed. A survey of state health departments related to radiation readiness was undertaken in 2010 by the Council of State and Territorial Epidemiologists (CSTE). States with nuclear power plants were instructed to consider their responses exclusive of capabilities and resources related to the plants given that the emergency response plans for nuclear power plants are specific and unique. Thirty-eight (76%) state health departments responded to the survey, including 26 of the 31 states with nuclear power plants. Specific strengths noted at the state level included that the majority of states had a written radiation response plan and most plans include a detailed section for communications issues during a radiation emergency. In addition, more than half of the states indicated that their relationship with federal partners is sufficient to provide resources for radiation emergencies, indicating the importance states placed on federal resources and expertise. Specific weaknesses are discussed and include that most states had completed little to no planning for public health surveillance to assess potential human health impacts of a radiation event; less than half had written plans to address exposure assessment, environmental sampling, human specimen collection and analysis, and human health assessment. Few reported having sufficient resources to do public health surveillance, radiation exposure assessment, laboratory functions and other capabilities. Levels of planning, resources and partnerships varied among states, those with nuclear power plants were better prepared. Gaps were evident in all states; however and additional training and resources are needed to ensure adequate levels of preparedness. Overall results of this assessment indicate that in most measures of public health capacity and capability, states are poorly prepared to adequately respond to a major radiation emergency event. Specific recommendations are noted in the discussion.

Item Response Data Analysis Using Stata Item Response Theory Package

ERIC Educational Resources Information Center

Yang, Ji Seung; Zheng, Xiaying

2018-01-01

The purpose of this article is to introduce and review the capability and performance of the Stata item response theory (IRT) package that is available from Stata v.14, 2015. Using a simulated data set and a publicly available item response data set extracted from Programme of International Student Assessment, we review the IRT package from…

Layerwise mechanics and finite element for the dynamic analysis of piezoelectric composite plates

NASA Technical Reports Server (NTRS)

Saravanos, Dimitris A.; Heyliger, Paul R.; Hopkins, Dale A.

1996-01-01

Laminate and structural mechanics for the analysis of laminated composite plate structures with piezoelectric actuators and sensors are presented. The theories implement layerwise representations of displacements and electric potential, and can model both the global and local electromechanical response of smart composite laminates. Finite-element formulations are developed for the quasi-static and dynamic analysis of smart composite structures containing piezoelectric layers. Comparisons with an exact solution illustrate the accuracy, robustness and capability of the developed mechanics to capture the global and local response of thin and/or thick laminated piezoelectric plates. Additional correlations and numerical applications demonstrate the unique capabilities of the mechanics in analyzing the static and free-vibration response of composite plates with distributed piezoelectric actuators and sensors.

Integration of Variable Speed Pumped Hydro Storage in Automatic Generation Control Systems

NASA Astrophysics Data System (ADS)

Fulgêncio, N.; Moreira, C.; Silva, B.

2017-04-01

Pumped storage power (PSP) plants are expected to be an important player in modern electrical power systems when dealing with increasing shares of new renewable energies (NRE) such as solar or wind power. The massive penetration of NRE and consequent replacement of conventional synchronous units will significantly affect the controllability of the system. In order to evaluate the capability of variable speed PSP plants participation in the frequency restoration reserve (FRR) provision, taking into account the expected performance in terms of improved ramp response capability, a comparison with conventional hydro units is presented. In order to address this issue, a three area test network was considered, as well as the corresponding automatic generation control (AGC) systems, being responsible for re-dispatching the generation units to re-establish power interchange between areas as well as the system nominal frequency. The main issue under analysis in this paper is related to the benefits of the fast response of variable speed PSP with respect to its capability of providing fast power balancing in a control area.

Environmental Response Laboratory Network (ERLN) Public Labs Fact Sheet

EPA Pesticide Factsheets

Outlines goals for participation in the Environmental Response Laboratory Network, and FAQs. They play an integral role in a coordinated and operational system of labs capable of efficiently and effectively responding to incidents.

Report of the Defense Science Board 2008 Summer Study on Capability Surprise. Volume 2: Supporting Papers

DTIC Science & Technology

2010-01-01

on Capability Surprise Volume II: Supporting Papers DTX-C January 2010 20100128212 This report is a product of the Defense Science Board (DSB...place within DOD or the interagency to help decide which events to act on aggressively, which to treat to a lesser degree, and which to ignore, at...three panels reporting herein agree on the need: • To establish a high-level organization, the Capability Assessment, Warning, and Response Office, to

A Feasibility Study on the Geophysical Response to Nanoparticles in the Subsurface

EPA Science Inventory

The research presented herein aims to determine if a spectral induced polarization (SIP) response exists due to nanoparticles in a saturated sand matrix. If a SIP response is realized in such an experimental setting, then it is feasible that SIP may be capable of delineating nano...

"It's Not so Much a Job but a Relationship": A Response to Romer and Walker

ERIC Educational Resources Information Center

O'Brien, John

2013-01-01

Romer and Walker's "Appreciative Inquiry," which obtained input from 16 capable personal assistants, challenges some influential assumptions about personal assistance and opens a way to think about the demanding work of developing capable and committed personal assistants. Attempts to depersonalize the relationship between people…

Structures and Materials Experimental Facilities and Capabilities Catalog

NASA Technical Reports Server (NTRS)

Horta, Lucas G. (Compiler); Kurtz-Husch, Jeanette D. (Compiler)

2000-01-01

The NASA Center of Excellent for Structures and Materials at Langley Research Center is responsible for conducting research and developing useable technology in the areas of advanced materials and processing technologies, durability, damage tolerance, structural concepts, advanced sensors, intelligent systems, aircraft ground operations, reliability, prediction tools, performance validation, aeroelastic response, and structural dynamics behavior for aerospace vehicles. Supporting the research activities is a complementary set of facilities and capabilities documented in this report. Because of the volume of information, the information collected was restricted in most cases to one page. Specific questions from potential customers or partners should be directed to the points of contacts provided with the various capabilities. Grouping of the equipment is by location as opposed to function. Geographical information of the various buildings housing the equipment is also provided. Since this is the first time that such an inventory is ever collected at Langley it is by no means complete. It is estimated that over 90 percent of the equipment capabilities at hand are included but equipment is continuously being updated and will be reported in the future.

Rotordynamics on the PC: Further Capabilities of ARDS

NASA Technical Reports Server (NTRS)

Fleming, David P.

1997-01-01

Rotordynamics codes for personal computers are now becoming available. One of the most capable codes is Analysis of RotorDynamic Systems (ARDS) which uses the component mode synthesis method to analyze a system of up to 5 rotating shafts. ARDS was originally written for a mainframe computer but has been successfully ported to a PC; its basic capabilities for steady-state and transient analysis were reported in an earlier paper. Additional functions have now been added to the PC version of ARDS. These functions include: 1) Estimation of the peak response following blade loss without resorting to a full transient analysis; 2) Calculation of response sensitivity to input parameters; 3) Formulation of optimum rotor and damper designs to place critical speeds in desirable ranges or minimize bearing loads; 4) Production of Poincard plots so the presence of chaotic motion can be ascertained. ARDS produces printed and plotted output. The executable code uses the full array sizes of the mainframe version and fits on a high density floppy disc. Examples of all program capabilities are presented and discussed.

Thrust vectoring systems

NASA Technical Reports Server (NTRS)

King, H. J.; Schnelker, D.; Ward, J. W.; Dulgeroff, C.; Vahrenkamp, R.

1972-01-01

The design, fabrication, and testing of thrust vectorable ion optical systems capable of controlling the thrust direction from both 5- and 30-cm diameter ion thrusters is described. Both systems are capable of greater than 10 deg thrust deflection in any azimuthal direction. The 5-cm system is electrostatic and hence has a short response time and minimal power consumption. It has recently been tested for more than 7500 hours on an operational thruster. The 30-cm system is mechanical, has a response time of the order of 1 min, and consumes less than 0.3% of the total system input power at full deflection angle.

5 CFR 1315.3 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... standardized information and electronic data exchange to the central management agency. Systems shall provide complete, timely, reliable, useful and consistent financial management information. Payment capabilities... Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES PROMPT PAYMENT § 1315.3 Responsibilities...

Small Space Launch: Origins & Challenges

NASA Astrophysics Data System (ADS)

Freeman, T.; Delarosa, J.

2010-09-01

The United States Space Situational Awareness capability continues to be a key element in obtaining and maintaining the high ground in space. Space Situational Awareness satellites are critical enablers for integrated air, ground and sea operations, and play an essential role in fighting and winning conflicts. The United States leads the world space community in spacecraft payload systems from the component level into spacecraft, and in the development of constellations of spacecraft. In the area of launch systems that support Space Situational Awareness, despite the recent development of small launch vehicles, the United States launch capability is dominated by an old, unresponsive and relatively expensive set of launchers in the Expandable, Expendable Launch Vehicles (EELV) platforms; Delta IV and Atlas V. The United States directed Air Force Space Command to develop the capability for operationally responsive access to space and use of space to support national security, including the ability to provide critical space capabilities in the event of a failure of launch or on-orbit capabilities. On 1 Aug 06, Air Force Space Command activated the Space Development & Test Wing (SDTW) to perform development, test and evaluation of Air Force space systems and to execute advanced space deployment and demonstration projects to exploit new concepts and technologies, and rapidly migrate capabilities to the warfighter. The SDTW charged the Launch Test Squadron (LTS) with the mission to develop the capability of small space launch, supporting government research and development space launches and missile defense target missions, with operationally responsive spacelift for Low-Earth-Orbit Space Situational Awareness assets as a future mission. This new mission created new challenges for LTS. The LTS mission tenets of developing space launches and missile defense target vehicles were an evolution from the squadrons previous mission of providing sounding rockets under the Rocket Sounding Launch Program (RSLP). The new mission tenets include shortened operational response periods criteria for the warfighter, while reducing the life-cycle development, production and launch costs of space launch systems. This presentation will focus on the technical challenges in transforming and integrating space launch vehicles and space craft vehicles for small space launch missions.

Turbine blade forced response prediction using FREPS

NASA Technical Reports Server (NTRS)

Murthy, Durbha, V.; Morel, Michael R.

1993-01-01

This paper describes a software system called FREPS (Forced REsponse Prediction System) that integrates structural dynamic, steady and unsteady aerodynamic analyses to efficiently predict the forced response dynamic stresses in axial flow turbomachinery blades due to aerodynamic and mechanical excitations. A flutter analysis capability is also incorporated into the system. The FREPS system performs aeroelastic analysis by modeling the motion of the blade in terms of its normal modes. The structural dynamic analysis is performed by a finite element code such as MSC/NASTRAN. The steady aerodynamic analysis is based on nonlinear potential theory and the unsteady aerodynamic analyses is based on the linearization of the non-uniform potential flow mean. The program description and presentation of the capabilities are reported herein. The effectiveness of the FREPS package is demonstrated on the High Pressure Oxygen Turbopump turbine of the Space Shuttle Main Engine. Both flutter and forced response analyses are performed and typical results are illustrated.

Cytarabine and daunorubicin for the treatment of acute myeloid leukemia.

PubMed

Murphy, Tracy; Yee, Karen W L

2017-11-01

Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3 + 7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3 + 7'. Somatic mutations in AML that are linked to chemoresistance to '3 + 7'will be discussed. Other topics covered include the novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and midostaurin in FLT3 mutated AML. Expert opinion: '3 + 7' continues to be the backbone of therapy for AML. However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy and hence, should be enrolled onto a clinical trial upfront. This will facilitate development of newer effective treatment strategies in AML. Patients with mutations that are associated with chemoresistance should be offered therapies which may circumvent or overcome these pathways.

A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium

PubMed Central

Parker, Aimée; Pin, Carmen; Carding, Simon R.; Watson, Alastair J. M.; Byrne, Helen M.

2017-01-01

Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions—uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales. PMID:28753601

A hierarchical Bayesian model for understanding the spatiotemporal dynamics of the intestinal epithelium.

PubMed

Maclaren, Oliver J; Parker, Aimée; Pin, Carmen; Carding, Simon R; Watson, Alastair J M; Fletcher, Alexander G; Byrne, Helen M; Maini, Philip K

2017-07-01

Our work addresses two key challenges, one biological and one methodological. First, we aim to understand how proliferation and cell migration rates in the intestinal epithelium are related under healthy, damaged (Ara-C treated) and recovering conditions, and how these relations can be used to identify mechanisms of repair and regeneration. We analyse new data, presented in more detail in a companion paper, in which BrdU/IdU cell-labelling experiments were performed under these respective conditions. Second, in considering how to more rigorously process these data and interpret them using mathematical models, we use a probabilistic, hierarchical approach. This provides a best-practice approach for systematically modelling and understanding the uncertainties that can otherwise undermine the generation of reliable conclusions-uncertainties in experimental measurement and treatment, difficult-to-compare mathematical models of underlying mechanisms, and unknown or unobserved parameters. Both spatially discrete and continuous mechanistic models are considered and related via hierarchical conditional probability assumptions. We perform model checks on both in-sample and out-of-sample datasets and use them to show how to test possible model improvements and assess the robustness of our conclusions. We conclude, for the present set of experiments, that a primarily proliferation-driven model suffices to predict labelled cell dynamics over most time-scales.

Effects of cooking methods on the iron and zinc contents in cowpea (Vigna unguiculata) to combat nutritional deficiencies in Brazil

PubMed Central

Pereira, Elenilda J.; Carvalho, Lucia M. J.; Dellamora-Ortiz, Gisela M.; Cardoso, Flávio S. N.; Carvalho, José L. V.; Viana, Daniela S.; Freitas, Sidinea C.; Rocha, Maurisrael M.

2014-01-01

Background Because iron deficiency anemia is prevalent in developing countries, determining the levels of iron and zinc in beans, the second most consumed staple food in Brazil, is essential, especially for the low-income people who experience a deficiency of these minerals in their diet. Objectives This study aimed to evaluate the effect of cooking methods by measuring the iron and zinc contents in cowpea cultivars before and after soaking to determine the retention of these minerals. Methods The samples were cooked in both regular pans and pressure cookers with and without previous soaking. Mineral analyses were carried out by Spectrometry of Inductively Coupled Plasma (ICP). Results The results showed high contents of iron and zinc in raw samples as well as in cooked ones, with the use of regular pan resulting in greater percentage of iron retention and the use of pressure cooker ensuring higher retention of zinc. Conclusions The best retention of iron was found in the BRS Aracê cultivar prepared in a regular pan with previous soaking. This cultivar may be indicated for cultivation and human consumption. The best retention of zinc was found for the BRS Tumucumaque cultivar prepared in a pressure cooker without previous soaking. PMID:24624050

Space technology: A study of the significance of recognition for innovators of spinoff technologies. 1993 activities/1994, 1995 plans

NASA Technical Reports Server (NTRS)

1994-01-01

During the past 30 years as NASA has conducted technology transfer programs, it has gained considerable experience - particularly pertaining to the processes. However, three areas have not had much scrutiny: the examination of the contributions of the individuals who have developed successful spinoffs, the commercial success of the spinoffs themselves, and the degree to which they are understood by the public. In short, there has been limited evaluation to measure the success of technology transfer efforts mandated by Congress. Research conducted during the first year of a three-year NASA grant to the United States Space Foundation has taken the initial steps toward measuring the success of methodologies to accomplish that Congressionally-mandated technology transfer. In particular, the US Space Foundation, in cooperation with ARAC, technology transfer experts; JKA, a nationally recognized themed entertainment design company; and top evaluation consultants, inaugurated and evaluated a fresh approach including commercial practices to encourage, motivate, and energize technology transfer by: recognizing already successful efforts (Space Technology Hall of Fame Award), drawing potential business and industrial players into the process (Space Commerce Expo), and informing and motivating the general public (Space Technology Hall of Fame public venues). The first year's efforts are documented and directions for the future are outlined.

Performance analysis of different tuning rules for an isothermal CSTR using integrated EPC and SPC

NASA Astrophysics Data System (ADS)

Roslan, A. H.; Karim, S. F. Abd; Hamzah, N.

2018-03-01

This paper demonstrates the integration of Engineering Process Control (EPC) and Statistical Process Control (SPC) for the control of product concentration of an isothermal CSTR. The objectives of this study are to evaluate the performance of Ziegler-Nichols (Z-N), Direct Synthesis, (DS) and Internal Model Control (IMC) tuning methods and determine the most effective method for this process. The simulation model was obtained from past literature and re-constructed using SIMULINK MATLAB to evaluate the process response. Additionally, the process stability, capability and normality were analyzed using Process Capability Sixpack reports in Minitab. Based on the results, DS displays the best response for having the smallest rise time, settling time, overshoot, undershoot, Integral Time Absolute Error (ITAE) and Integral Square Error (ISE). Also, based on statistical analysis, DS yields as the best tuning method as it exhibits the highest process stability and capability.

Perform - A performance optimizing computer program for dynamic systems subject to transient loadings

NASA Technical Reports Server (NTRS)

Pilkey, W. D.; Wang, B. P.; Yoo, Y.; Clark, B.

1973-01-01

A description and applications of a computer capability for determining the ultimate optimal behavior of a dynamically loaded structural-mechanical system are presented. This capability provides characteristics of the theoretically best, or limiting, design concept according to response criteria dictated by design requirements. Equations of motion of the system in first or second order form include incompletely specified elements whose characteristics are determined in the optimization of one or more performance indices subject to the response criteria in the form of constraints. The system is subject to deterministic transient inputs, and the computer capability is designed to operate with a large linear programming on-the-shelf software package which performs the desired optimization. The report contains user-oriented program documentation in engineering, problem-oriented form. Applications cover a wide variety of dynamics problems including those associated with such diverse configurations as a missile-silo system, impacting freight cars, and an aircraft ride control system.

The effect of platinum precursor concentrations on chlorine sensing characteristics of platinum nanoparticles-loaded single walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Choi, Sun-Woo; Byun, Young Tae

2018-03-01

The correlation between platinum (Pt) functionalization and chlorine (Cl2) sensing capability in single-walled carbon nanotubes (SWCNTs) was investigated. Utilizing a photoreduction technique via ultraviolet (UV) irradiation, the Pt nanoparticles (NPs) with various diameters of 7-80 nm, which were controlled by Pt precursor concentrations, were successfully functionalized on the sidewalls of SWCNTs. The discrete Pt NP-loaded SWCNTs exhibited significantly enhanced response value (-(ΔR/R0) × 100 = 33.8%) for 1 ppm Cl2 at room temperature (25 °C) compared with that (no response) of pure SWCNTs. On the other hand, in case of continuous Pt NP-loaded SWCNTs, Cl2 sensing capabilities were significantly degraded. The Cl2 sensing capabilities of fabricated sensors tended to correlate with geometric configurations of the catalytic Pt NPs on the sidewalls of SWCNTs, due to differences in the electron pathway.

Modal forced vibration analysis of aerodynamically excited turbosystems

NASA Technical Reports Server (NTRS)

Elchuri, V.

1985-01-01

Theoretical aspects of a new capability to determine the vibratory response of turbosystems subjected to aerodynamic excitation are presented. Turbosystems such as advanced turbopropellers with highly swept blades, and axial-flow compressors and turbines can be analyzed using this capability. The capability has been developed and implemented in the April 1984 release of the general purpose finite element program NASTRAN. The dynamic response problem is addressed in terms of the normal modal coordinates of these tuned rotating cyclic structures. Both rigid and flexible hubs/disks are considered. Coriolis and centripetal accelerations, as well as differential stiffness effects are included. Generally non-uniform steady inflow fields and uniform flow fields arbitrarily inclined at small angles with respect to the axis of rotation of the turbosystem are considered sources of aerodynamic excitation. The spatial non-uniformities are considered to be small deviations from a principally uniform inflow. Subsonic and supersonic relative inflows are addressed, with provision for linearly interpolating transonic airloads.

Attitudes toward the capabilities of deaf and hard of hearing adults: insights from the parents of deaf and hard of hearing children.

PubMed

Crowe, Kathryn; McLeod, Sharynne; McKinnon, David H; Ching, Teresa Y C

2015-01-01

Children who are d/Deaf and hard of hearing (DHH) grow up in environments influenced by their parents' attitudes, which may facilitate or impede these children's development and participation (World Health Organization, 2007). The attitudes of 152 Australian parents of DHH children ages 3 years 7 months to 9 years 5 months (M = 6 years 5 months) were investigated with the Opinions About Deaf People Scale (Berkay, Gardner, & Smith, 1995a). The parents' responses showed very positive attitudes toward the capabilities of DHH adults, particularly on items describing their intellectual and vocational capabilities. Parents' responses to most of the items on the scale were positively skewed, raising questions about its validity as a research tool when used with parents of DHH children. The study findings suggest that for these children, parents' attitudes may facilitate rather than present an environmental barrier to their development.

Three-dimensional infrared metamaterial with asymmetric transmission

DOE PAGES

Kenanakis, George; Xomalis, Aggelos; Selimis, Alexandros; ...

2015-01-14

A novel three-dimensional (3D) metallic metamaterial structure with asymmetric transmission for linear polarization is demonstrated in the infrared spectral region. The structure was fabricated by direct laser writing and selective electroless silver coating, a straightforward, novel technique producing mechanically and chemically stable 3D photonic structures. The structure unit cell is composed of a pair of conductively coupled magnetic resonators, and the asymmetric transmission response results from interplay of electric and magnetic responses; this equips the structure with almost total opaqueness along one propagation direction versus satisfying transparency along the opposite one. It also offers easily adjustable impedance, 90° one-way puremore » optical activity and backward propagation possibility, resulting thus in unique capabilities in polarization control and isolation applications. We show also that scaling down the structure can make it capable of exhibiting its asymmetric transmission and its polarization capabilities in the optical region.« less

Social policies related to parenthood and capabilities of Slovenian parents.

PubMed

Mrčela, Aleksandra Kanjuo; Sadar, Nevenka Černigoj

2011-01-01

We apply Sen's capability approach to evaluate the capabilities of Slovenian parents to reconcile paid work and family in the context of the transition to a market economy. We examine how different levels of capabilities together affect the work–life balance (WLB) of employed parents. We combine both quantitative and qualitative methodological approaches. The results of our quantitative and qualitative research show that increased precariousness of employment and intensification of work create gaps between the legal and normative possibilities for successful reconciliation strategies and actual use of such arrangements in Slovenia. The existing social policies and the acceptance of gender equality in the sphere of paid work enhance capabilities for reconciliation of paid work and parenthood, whereas the intensification of working lives, the dominance of paid work over other parts of life, and the acceptance of gender inequalities in parental and household responsibilities limit parents’ capabilities to achieve WLB.

Evidence for Response Bias as a Source of Error Variance in Applied Assessment

ERIC Educational Resources Information Center

McGrath, Robert E.; Mitchell, Matthew; Kim, Brian H.; Hough, Leaetta

2010-01-01

After 100 years of discussion, response bias remains a controversial topic in psychological measurement. The use of bias indicators in applied assessment is predicated on the assumptions that (a) response bias suppresses or moderates the criterion-related validity of substantive psychological indicators and (b) bias indicators are capable of…

Automated Analysis of Short Responses in an Interactive Synthetic Tutoring System for Introductory Physics

ERIC Educational Resources Information Center

Nakamura, Christopher M.; Murphy, Sytil K.; Christel, Michael G.; Stevens, Scott M.; Zollman, Dean A.

2016-01-01

Computer-automated assessment of students' text responses to short-answer questions represents an important enabling technology for online learning environments. We have investigated the use of machine learning to train computer models capable of automatically classifying short-answer responses and assessed the results. Our investigations are part…

IRTPRO 2.1 for Windows (Item Response Theory for Patient-Reported Outcomes)

ERIC Educational Resources Information Center

Paek, Insu; Han, Kyung T.

2013-01-01

This article reviews a new item response theory (IRT) model estimation program, IRTPRO 2.1, for Windows that is capable of unidimensional and multidimensional IRT model estimation for existing and user-specified constrained IRT models for dichotomously and polytomously scored item response data. (Contains 1 figure and 2 notes.)

30 CFR 254.30 - When must I revise my response plan?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES LOCATED SEAWARD OF THE COAST LINE Oil-Spill Response Plans for Outer Continental Shelf Facilities § 254.30 When must I revise... name(s) or capabilities of the oil spill removal organizations cited in the plan; or (4) There is a...

30 CFR 254.30 - When must I revise my response plan?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 254.30 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES LOCATED SEAWARD OF THE COAST LINE Oil-Spill Response Plans... transported at the facility; (3) There is a change in the name(s) or capabilities of the oil spill removal...

Physiological responses induced by emotion-eliciting films.

PubMed

Fernández, Cristina; Pascual, Juan C; Soler, Joaquim; Elices, Matilde; Portella, Maria J; Fernández-Abascal, Enrique

2012-06-01

Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear.

Maneuver Warfare in Cyberspace

DTIC Science & Technology

1997-01-01

government departments and agencies; (2) National security and military strategies must outline a response to the threats and opportunities of cyber ... warfare ; and (3) the Department of Defense’s offensive and defensive responsibilities, parameters, and capabilities for strategic information warfare need

International Space Station Environmental Control and Life Support Emergency Response Verification for Node 1

NASA Technical Reports Server (NTRS)

Williams, David E.

2008-01-01

The International Space Station (ISS) Node 1 Environmental Control and Life Support (ECLS) System is comprised of five subsystems: Atmosphere Control and Supply (ACS), Atmosphere Revitalization (AR), Fire Detection and Suppression (FDS), Temperature and Humidity Control (THC), and Water Recovery and Management (WRM). This paper provides a summary of the Node 1 Emergency Response capability, which includes nominal and off-nominal FDS operation, off nominal ACS operation, and off-nominal THC operation. These subsystems provide the capability to help aid the crew members during an emergency cabin depressurization, a toxic spill, or a fire. The paper will also provide a discussion of the detailed Node 1 ECLS Element Verification methodologies for operation of the Node 1 Emergency Response hardware operations utilized during the Qualification phase.

Biocatalytic Stimuli-Responsive Asymmetric Triblock Terpolymer Membranes for Localized Permeability Gating.

PubMed

Poole, Jennifer L; Donahue, Scott; Wilson, David; Li, Yuk Mun; Zhang, Qi; Gu, Yibei; Ferebee, Rachel; Lu, Zhao; Dorin, Rachel Mika; Hancock, Lawrence F; Takiff, Larry; Hakem, Ilhem F; Bockstaller, Michael R; Wiesner, Ulrich; Walker, Jeremy

2017-10-01

The functionalization with phosphotriesterase of poly(isoprene-b-styrene-b-4-vinylpyridine)-based nanoporous membranes fabricated by self-assembly and nonsolvent induced phase separation (SNIPS) is shown to enable dynamically responsive membranes capable of substrate-specific and localized gating response. Integration of the SNIPS process with macroporous nylon support layers yields mechanically robust textile-type films with high moisture vapor transport rates that display rapid and local order-of-magnitude modulation of permeability. The simplicity of the fabrication process that is compatible with large-area fabrication along with the versatility and efficacy of enzyme reactivity offers intriguing opportunities for engineered biomimetic materials that are tailored to respond to a complex range of external parameters, providing sensing, protection, and remediation capabilities. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cambio : a file format translation and analysis application for the nuclear response emergency community.

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

Lasche, George P.

2009-10-01

Cambio is an application intended to automatically read and display any spectrum file of any format in the world that the nuclear emergency response community might encounter. Cambio also provides an analysis capability suitable for HPGe spectra when detector response and scattering environment are not well known. Why is Cambio needed: (1) Cambio solves the following problem - With over 50 types of formats from instruments used in the field and new format variations appearing frequently, it is impractical for every responder to have current versions of the manufacturer's software from every instrument used in the field; (2) Cambio convertsmore » field spectra to any one of several common formats that are used for analysis, saving valuable time in an emergency situation; (3) Cambio provides basic tools for comparing spectra, calibrating spectra, and isotope identification with analysis suited especially for HPGe spectra; and (4) Cambio has a batch processing capability to automatically translate a large number of archival spectral files of any format to one of several common formats, such as the IAEA SPE or the DHS N42. Currently over 540 analysts and members of the nuclear emergency response community worldwide are on the distribution list for updates to Cambio. Cambio users come from all levels of government, university, and commercial partners around the world that support efforts to counter terrorist nuclear activities. Cambio is Unclassified Unlimited Release (UUR) and distributed by internet downloads with email notifications whenever a new build of Cambio provides for new formats, bug fixes, or new or improved capabilities. Cambio is also provided as a DLL to the Karlsruhe Institute for Transuranium Elements so that Cambio's automatic file-reading capability can be included at the Nucleonica web site.« less

Capabilities of the RENEB network for research and large scale radiological and nuclear emergency situations.

PubMed

Monteiro Gil, Octávia; Vaz, Pedro; Romm, Horst; De Angelis, Cinzia; Antunes, Ana Catarina; Barquinero, Joan-Francesc; Beinke, Christina; Bortolin, Emanuela; Burbidge, Christopher Ian; Cucu, Alexandra; Della Monaca, Sara; Domene, Mercedes Moreno; Fattibene, Paola; Gregoire, Eric; Hadjidekova, Valeria; Kulka, Ulrike; Lindholm, Carita; Meschini, Roberta; M'Kacher, Radhia; Moquet, Jayne; Oestreicher, Ursula; Palitti, Fabrizio; Pantelias, Gabriel; Montoro Pastor, Alegria; Popescu, Irina-Anca; Quattrini, Maria Cristina; Ricoul, Michelle; Rothkamm, Kai; Sabatier, Laure; Sebastià, Natividad; Sommer, Sylwester; Terzoudi, Georgia; Testa, Antonella; Trompier, François; Vral, Anne

2017-01-01

To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These capabilities include available biodosimetry techniques, infrastructure, human resources (existing trained staff), financial and organizational resources (including the role of national contact points and their articulation with other stakeholders in emergency response) as well as robust quality control/assurance systems. A survey was prepared and sent to the RENEB partners in order to acquire information about the existing, operational techniques and infrastructure in the laboratories of the different RENEB countries and to assess the capacity of response in the event of radiological or nuclear accident involving mass casualties. The survey focused on several main areas: laboratory's general information, country and staff involved in biological and physical dosimetry; retrospective assays used, the number of assays available per laboratory and other information related to biodosimetry and emergency preparedness. Following technical intercomparisons amongst RENEB members, an update of the survey was performed one year later concerning the staff and the available assays. The analysis of RENEB questionnaires allowed a detailed assessment of existing capacity of the RENEB network to respond to nuclear and radiological emergencies. This highlighted the key importance of international cooperation in order to guarantee an effective and timely response in the event of radiological or nuclear accidents involving a considerable number of casualties. The deployment of the scientific and technical capabilities existing within the RENEB network members seems mandatory, to help other countries with less or no capacity for biological or physical dosimetry, or countries overwhelmed in case of a radiological or nuclear accident involving a large number of individuals.

A Developmental Model of Financial Capability: A Framework for Promoting a Successful Transition to Adulthood

ERIC Educational Resources Information Center

Serido, Joyce; Shim, Soyeon; Tang, Chuanyi

2013-01-01

This study proposes a developmental model of financial capability to understand the process by which young adults acquire the financial knowledge and behaviors needed to manage full-time adult social roles and responsibilities. The model integrates financial knowledge, financial self-beliefs, financial behavior, and well-being into a single…

A Human Development and Capabilities "Prospective Analysis" of Global Higher Education Policy

ERIC Educational Resources Information Center

Walker, Melanie

2010-01-01

In global times, university education policy that holds the greatest promise for social responsibility is the focus here; the argument made is that such policy ought to be conceptualised using a normative human development and capabilities approach, drawing on the work of Amartya Sen and Martha Nussbaum. Their ideas offer a values-based way of…

Analytical capabilities and services of Lawrence Livermore Laboratory's General Chemistry Division. [Methods available at Lawrence Livermore

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

Gutmacher, R.; Crawford, R.

This comprehensive guide to the analytical capabilities of Lawrence Livermore Laboratory's General Chemistry Division describes each analytical method in terms of its principle, field of application, and qualitative and quantitative uses. Also described are the state and quantity of sample required for analysis, processing time, available instrumentation, and responsible personnel.

Meeting the Growing Demand for Sustainability-Focused Management Education: A Case Study of a PRME Academic Institution

ERIC Educational Resources Information Center

Young, Suzanne; Nagpal, Swati

2013-01-01

The current business landscape has created the impetus to develop management graduates with capabilities that foster responsible leadership and sustainability. Through the lens of Gitsham's 3C Model (Complexity, Context and Connection) of graduate capabilities, this paper discusses the experience of implementing the United Nations Principles for…

Automated Pilot Performance Assessment in the T-37: A Feasibility Study. Final Report (May 1968-April 1971).

ERIC Educational Resources Information Center

Knoop, Patricia A.; Welde, William L.

Air Force investigators conducted a three year program to develop a capability for automated quantification and assessment of in-flight pilot performance. Such a capability enhances pilot training by making ratings more objective, valid, reliable and sensitive, and by freeing instructors from rating responsibilities, allowing them to concentrate…

Performance of district disaster management teams after undergoing an operational level planners' training in Uganda.

PubMed

Orach, Christopher Garimol; Mayega, Roy William; Woboya, Vincent; William, Bazeyo

2013-06-01

Uganda is vulnerable to several natural, man-made and a hybrid of disasters including drought, famine, floods, warfare, and disease outbreaks. We assessed the district disaster team's performance, roles and experiences following the training. The disasters most commonly experienced by the district teams were epidemics of diseases in humans (7 of 12), animals (epizoonotics) (3 of 12) and crops (3 of 12); hailstorms and floods (3 of 12). The capabilities viewed most useful for management of disasters were provision of health care services (9/12) and response management (8 of 12). The capability domains most often consulted during the disasters were general response management (31%), health services (29%) and water and sanitation (17%). The skills areas perceived to be vital following the training were response to epidemics 10/12, disaster management planning 8/12, hazards and vulnerability analysis 7/12 and principles of disaster planning 7/12 respectively. Main challenges mentioned by district teams were inadequacy of finance and logistics, lack of commitment by key partners towards disaster preparedness and response. The most common disaster experienced disasters related to outbreaks of diseases in man, animals and crops. The most frequently applied capabilities were response management and provision of emergency health services. The activities most frequently implemented following disaster management teams training were conducting planning meetings, refinement of plans and dissemination of skills gained. The main challenges were related to limited budget allocations and legal frameworks for disaster management that should be addressed by both central and local governments.

Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

PubMed

Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

2016-04-06

The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

Do capability and functioning differ? A study of U.K. survey responses

PubMed Central

2017-01-01

Summary A core feature of the capability approach is that a person's capabilities (what they are able to do and be in their life) can differ from their functionings (what they actually do and are in their life). However, the degree to which capability and functioning differ in practice is unclear. This paper investigates this issue, focusing on capability and functioning differences (CFD) across different aspects of life and different individuals. In the study, the ICECAP‐A capability questionnaire was modified to measure both functionings and capabilities and was completed by U.K.‐based convenience sample of 943 people. Around one third of people reported CFD in at least one area of their life, most commonly in terms of their “achievement.” People were more likely to report CFD when they had a degree‐level education and when they had impaired health. An additional finding was that capability varied more with education whereas functioning varied more with health status. This finding needs further examination, but it suggests that the choice of evaluative space may influence how priorities are set for public spending. PMID:28944529

Dynamic Behavior of Sand: Annual Report FY 11

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

Antoun, T; Herbold, E; Johnson, S

2012-03-15

Currently, design of earth-penetrating munitions relies heavily on empirical relationships to estimate behavior, making it difficult to design novel munitions or address novel target situations without expensive and time-consuming full-scale testing with relevant system and target characteristics. Enhancing design through numerical studies and modeling could help reduce the extent and duration of full-scale testing if the models have enough fidelity to capture all of the relevant parameters. This can be separated into three distinct problems: that of the penetrator structural and component response, that of the target response, and that of the coupling between the two. This project focuses onmore » enhancing understanding of the target response, specifically granular geomaterials, where the temporal and spatial multi-scale nature of the material controls its response. As part of the overarching goal of developing computational capabilities to predict the performance of conventional earth-penetrating weapons, this project focuses specifically on developing new models and numerical capabilities for modeling sand response in ALE3D. There is general recognition that granular materials behave in a manner that defies conventional continuum approaches which rely on response locality and which degrade in the presence of strong response nonlinearities, localization, and phase gradients. There are many numerical tools available to address parts of the problem. However, to enhance modeling capability, this project is pursuing a bottom-up approach of building constitutive models from higher fidelity, smaller spatial scale simulations (rather than from macro-scale observations of physical behavior as is traditionally employed) that are being augmented to address the unique challenges of mesoscale modeling of dynamically loaded granular materials. Through understanding response and sensitivity at the grain-scale, it is expected that better reduced order representations of response can be formulated at the continuum scale as illustrated in Figure 1 and Figure 2. The final result of this project is to implement such reduced order models in the ALE3D material library for general use.« less

Dynamic malware analysis using IntroVirt: a modified hypervisor-based system

NASA Astrophysics Data System (ADS)

White, Joshua S.; Pape, Stephen R.; Meily, Adam T.; Gloo, Richard M.

2013-05-01

In this paper, we present a system for Dynamic Malware Analysis which incorporates the use of IntroVirt™. IntroVirt is an introspective hypervisor architecture and infrastructure that supports advanced analysis techniques for stealth-malwareanalysis. This system allows for complete guest monitoring and interaction, including the manipulation and blocking of system calls. IntroVirt is capable of bypassing virtual machine detection capabilities of even the most sophisticated malware, by spoofing returns to system call responses. Additional fuzzing capabilities can be employed to detect both malware vulnerabilities and polymorphism.

76 FR 62420 - Statement of Organization, Functions and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... leadership, consultation, training, and management services for HRSA's enterprise computing environment; (2... responsibility with improved security management capabilities and improved alignment of current security... responsible for the organization, management, and administrative functions necessary to carry out the...

Pressure Testing of a Minimum Gauge PRSEUS Panel

NASA Technical Reports Server (NTRS)

Lovejoy, Andrew J.; Rouse, Marshall; Linton, Kim A.; Li, Victor P.

2011-01-01

Advanced aircraft configurations that have been developed to increase fuel efficiency require advanced, novel structural concepts capable of handling the unique load conditions that arise. One such concept is the Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) developed by the Boeing Company. The PRSEUS concept is being investigated by NASA s Environmentally Responsible Aviation (ERA) Program for use in a hybrid-wing body (HWB) aircraft. This paper summarizes the analysis and test of a PRSEUS panel subjected to internal pressure, the first such pressure test for this structural concept. The pressure panel used minimum gauge skin, with stringer and frame configurations consistent with previous PRSEUS tests. Analysis indicated that for the minimum gauge skin panel, the stringer locations exhibit fairly linear response, but the skin bays between the stringers exhibit nonlinear response. Excellent agreement was seen between nonlinear analysis and test results in the critical portion at the center of the panel. The pristine panel was capable of withstanding the required 18.4 psi pressure load condition without exhibiting any damage. The impacted panel was capable of withstanding a pressure load in excess of 28 psi before initial failure occurred at the center stringer, and the panel was capable of sustaining increased pressure load after the initial failure. This successful PRSEUS panel pressure panel test was a critical step in the building block approach for enabling the use of this advanced structural concept on future aircraft, such as the HWB.

What is a global manager?

PubMed

Bartlett, C A; Ghoshal, S

1992-01-01

To compete around the world, a company needs three strategic capabilities: global-scale efficiency, local responsiveness, and the ability to leverage learning worldwide. No single "global" manager can build these capabilities. Rather, groups of specialized managers must integrate assets, resources, and people in diverse operating units. Such managers are made, not born. And how to make them is--and must be--the foremost question for corporate managers. Drawing on their research with leading transnational corporations, Christopher Bartlett and Sumantra Ghoshal identify three types of global managers. They also illustrate the responsibilities each position involves through a close look at the careers of successful executives: Leif Johansson of Electrolux, Howard Gottlieb of NEC, and Wahib Zaki of Procter & Gamble. The first type is the global business or product-division manager who must build worldwide efficiency and competitiveness. These managers recognize cross-border opportunities and risks as well as link activities and capabilities around the world. The second is the country manager whose unit is the building block for worldwide operations. These managers are responsible for understanding and interpreting local markets, building local resources and capabilities, and contributing to--and participating in--the development of global strategy. Finally, there are worldwide functional specialists--the managers whose potential is least appreciated in many traditional multinational companies. To transfer expertise from one unit to another and leverage learning, these managers must scan the company for good ideas and best practice, cross-pollinate among units, and champion innovations with worldwide applications.

Explosive detection technology

NASA Astrophysics Data System (ADS)

Doremus, Steven; Crownover, Robin

2017-05-01

The continuing proliferation of improvised explosive devices is an omnipresent threat to civilians and members of military and law enforcement around the world. The ability to accurately and quickly detect explosive materials from a distance would be an extremely valuable tool for mitigating the risk posed by these devices. A variety of techniques exist that are capable of accurately identifying explosive compounds, but an effective standoff technique is still yet to be realized. Most of the methods being investigated to fill this gap in capabilities are laser based. Raman spectroscopy is one such technique that has been demonstrated to be effective at a distance. Spatially Offset Raman Spectroscopy (SORS) is a technique capable of identifying chemical compounds inside of containers, which could be used to detect hidden explosive devices. Coherent Anti-Stokes Raman Spectroscopy (CARS) utilized a coherent pair of lasers to excite a sample, greatly increasing the response of sample while decreasing the strength of the lasers being used, which significantly improves the eye safety issue that typically hinders laser-based detection methods. Time-gating techniques are also being developed to improve the data collection from Raman techniques, which are often hindered fluorescence of the test sample in addition to atmospheric, substrate, and contaminant responses. Ultraviolet based techniques have also shown significant promise by greatly improved signal strength from excitation of resonance in many explosive compounds. Raman spectroscopy, which identifies compounds based on their molecular response, can be coupled with Laser Induced Breakdown Spectroscopy (LIBS) capable of characterizing the sample's atomic composition using a single laser.

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

Powell, D.R.; Hutchinson, J.L.

Eagle 11 is a prototype analytic model derived from the integration of the low resolution Eagle model with the high resolution SIMNET model. This integration promises a new capability to allow for a more effective examination of proposed or existing combat systems that could not be easily evaluated using either Eagle or SIMNET alone. In essence, Eagle II becomes a multi-resolution combat model in which simulated combat units can exhibit both high and low fidelity behavior at different times during model execution. This capability allows a unit to behave in a highly manner only when required, thereby reducing the overallmore » computational and manpower requirements for a given study. In this framework, the SIMNET portion enables a highly credible assessment of the performance of individual combat systems under consideration, encompassing both engineering performance and crew capabilities. However, when the assessment being conducted goes beyond system performance and extends to questions of force structure balance and sustainment, then SISMNET results can be used to ``calibrate`` the Eagle attrition process appropriate to the study at hand. Advancing technologies, changes in the world-wide threat, requirements for flexible response, declining defense budgets, and down-sizing of military forces motivate the development of manpower-efficient, low-cost, responsive tools for combat development studies. Eagle and SIMNET both serve as credible and useful tools. The integration of these two models promises enhanced capabilities to examine the broader, deeper, more complex battlefield of the future with higher fidelity, greater responsiveness and low overall cost.« less

Pilot-in-the-Loop Evaluation of a Yaw Rate to Throttle Feedback Control with Enhanced Engine Response

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.; Guo, Ten-Huei; Sowers, T. Shane; Chicatelli, Amy K.; Fulton, Christopher E.; May, Ryan D.; Owen, A. Karl

2012-01-01

This paper describes the implementation and evaluation of a yaw rate to throttle feedback system designed to replace a damaged rudder. It can act as a Dutch roll damper and as a means to facilitate pilot input for crosswind landings. Enhanced propulsion control modes were implemented to increase responsiveness and thrust level of the engine, which impact flight dynamics and performance. Piloted evaluations were performed to determine the capability of the engines to substitute for the rudder function under emergency conditions. The results showed that this type of implementation is beneficial, but the engines' capability to replace the rudder is limited.

Lizard tail regeneration as an instructive model of enhanced healing capabilities in an adult amniote.

PubMed

Lozito, Thomas P; Tuan, Rocky S

2017-03-01

The ability to regenerate damaged or lost tissues has remained the lofty goal of regenerative medicine. Unfortunately, humans, like most mammals, suffer from very minimal natural regenerative capabilities. Certain non-mammalian animal species, however, are not so limited in their healing capabilities, and several have attracted the attention of researchers hoping to recreate enhanced healing responses in humans. This review focuses on one such animal group with remarkable regenerative abilities, the lizards. As the closest relatives of mammals that exhibit enhanced regenerative abilities as adults, lizards potentially represent the most relevant model for direct comparison and subsequent improvement of mammalian healing. Lizards are able to regenerate amputated tails and exhibit adaptations that both limit tissue damage in response to injury and initiate coordinated regenerative responses. This review summarizes the salient aspects of lizard tail regeneration as they relate to the overall regenerative process and also presents the relevant information pertaining to regrowth of specific tissues, including skeletal, muscular, nervous, and vascular tissues. The goal of this review is to introduce the topic of lizard tail regeneration to new audiences with the hope of expanding the knowledge base of this underutilized but potentially powerful model organism.

A Context-Aware Model to Provide Positioning in Disaster Relief Scenarios

PubMed Central

Moreno, Daniel; Ochoa, Sergio F.; Meseguer, Roc

2015-01-01

The effectiveness of the work performed during disaster relief efforts is highly dependent on the coordination of activities conducted by the first responders deployed in the affected area. Such coordination, in turn, depends on an appropriate management of geo-referenced information. Therefore, enabling first responders to count on positioning capabilities during these activities is vital to increase the effectiveness of the response process. The positioning methods used in this scenario must assume a lack of infrastructure-based communication and electrical energy, which usually characterizes affected areas. Although positioning systems such as the Global Positioning System (GPS) have been shown to be useful, we cannot assume that all devices deployed in the area (or most of them) will have positioning capabilities by themselves. Typically, many first responders carry devices that are not capable of performing positioning on their own, but that require such a service. In order to help increase the positioning capability of first responders in disaster-affected areas, this paper presents a context-aware positioning model that allows mobile devices to estimate their position based on information gathered from their surroundings. The performance of the proposed model was evaluated using simulations, and the obtained results show that mobile devices without positioning capabilities were able to use the model to estimate their position. Moreover, the accuracy of the positioning model has been shown to be suitable for conducting most first response activities. PMID:26437406

African-American Stories and Literary Responses: Does a Child's Ethnicity Affect the Focus of a Response?

ERIC Educational Resources Information Center

Altieri, Jennifer L.

1993-01-01

Examines the written responses of Hispanic, African-American and Caucasian elementary students after listening to various African-American stories to see whether engagement with text is related to student's ethnicity. Finds that students were equally capable of engagement in the African-American stories regardless of their ethnicity. (RS)

Item Response Models for Examinee-Selected Items

ERIC Educational Resources Information Center

Wang, Wen-Chung; Jin, Kuan-Yu; Qiu, Xue-Lan; Wang, Lei

2012-01-01

In some tests, examinees are required to choose a fixed number of items from a set of given items to answer. This practice creates a challenge to standard item response models, because more capable examinees may have an advantage by making wiser choices. In this study, we developed a new class of item response models to account for the choice…

Sierra/SolidMechanics 4.48 User's Guide: Addendum for Shock Capabilities.

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

Plews, Julia A.; Crane, Nathan K; de Frias, Gabriel Jose

This is an addendum to the Sierra/SolidMechanics 4.48 User's Guide that documents additional capabilities available only in alternate versions of the Sierra/SolidMechanics (Sierra/SM) code. These alternate versions are enhanced to provide capabilities that are regulated under the U.S. Department of State's International Traffic in Arms Regulations (ITAR) export-control rules. The ITAR regulated codes are only distributed to entities that comply with the ITAR export-control requirements. The ITAR enhancements to Sierra/SM in- clude material models with an energy-dependent pressure response (appropriate for very large deformations and strain rates) and capabilities for blast modeling. Since this is an addendum to the standardmore » Sierra/SM user's guide, please refer to that document first for general descriptions of code capability and use.« less

Technology Risk Mitigation Research and Development for the Matter-Radiation Interactions in Extremes (MaRIE) Project

NASA Astrophysics Data System (ADS)

Barnes, Cris W.; Fernández, Juan; Hartsfield, Thomas; Sandberg, Richard; Sheffield, Richard; Tapia, John P.; Wang, Zhehui

2017-06-01

NNSA does not have a capability to understand and test the response of materials and conditions necessary to determine the linkages between microstructure of materials and performance in extreme weapons-relevant environments. Required is an x-ray source, coherent to optimize imaging capability, brilliant and high repetition-rate to address all relevant time scales, and with high enough energy to see into and through the amount of material in the middle or mesoscale where microstructure determines materials response. The Department of Energy has determined there is a mission need for a MaRIE Project to deliver this capability. There are risks to the Project to successfully deliver all the technology needed to provide the capability for the mission need and to use those photons to control the time-dependent production and performance of materials. The present technology risk mitigation activities for the MaRIE project are: developing ultrafast high-energy x-ray detectors, combining the data from several imaging probes to obtain multi-dimensional information about the sample, and developing techniques for bulk dynamic measurements of temperature. This talk will describe these efforts and other critical technology elements requiring future investment by the project.

Rapid Application of Space Effects for the Small Satellites Systems and Services Symposium

NASA Technical Reports Server (NTRS)

Tsairides, Demosthenes; Finley, Charles; Moretti, George

2016-01-01

NASA Ames Research Center (ARC) has engaged Military Branches, the Department of Defense, and other Government Agencies in successful partnerships to design, develop, deliver and support various space effects capabilities and space vehicles on timeline of need. Contracts with Industry are in place to execute operational and enabler missions using physical and informational infrastructures including Responsive Manufacturing capabilities and Digital Assurance. The intent is to establish a secure, web-enabled "store front" for ordering and delivering any capabilities required as defined by the users and directed by NASA ARC and Partner Organizations. The capabilities are envisioned to cover a broad range and include 6U CubeSats, 50-100 kg Space Vehicles, Modular Space Vehicle architecture variations, as well as rapid payload integration on various Bus options. The paper will discuss the efforts underway to demonstrate autonomous manufacturing of low-volume, high-value assets, to validate the ability of autonomous digital techniques to provide Mission Assurance, and to demonstrate cost savings through the identification, characterization, and utilization of Responsive Space components. The culmination of this effort will be the integration of several 6U satellites and their launch in 2016.

Micromechanics and Piezo Enhancements of HyperSizer

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Bednarcyk, Brett A.; Yarrington, Phillip; Collier, Craig S.

2006-01-01

The commercial HyperSizer aerospace-composite-material-structure-sizing software has been enhanced by incorporating capabilities for representing coupled thermal, piezoelectric, and piezomagnetic effects on the levels of plies, laminates, and stiffened panels. This enhancement is based on a formulation similar to that of the pre-existing HyperSizer capability for representing thermal effects. As a result of this enhancement, the electric and/or magnetic response of a material or structure to a mechanical or thermal load, or its mechanical response to an applied electric or magnetic field can be predicted. In another major enhancement, a capability for representing micromechanical effects has been added by establishment of a linkage between HyperSizer and Glenn Research Center s Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC) computer program, which was described in several prior NASA Tech Briefs articles. The linkage enables Hyper- Sizer to localize to the fiber and matrix level rather than only to the ply level, making it possible to predict local failures and to predict properties of plies from those of the component fiber and matrix materials. Advanced graphical user interfaces and database structures have been developed to support the new HyperSizer micromechanics capabilities.

Requirements Development for Interoperability Simulation Capability for Law Enforcement

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

Holter, Gregory M.

2004-05-19

The National Counterdrug Center (NCC) was initially authorized by Congress in FY 1999 appropriations to create a simulation-based counterdrug interoperability training capability. As the lead organization for Research and Analysis to support the NCC, the Pacific Northwest National Laboratory (PNNL) was responsible for developing the requirements for this interoperability simulation capability. These requirements were structured to address the hardware and software components of the system, as well as the deployment and use of the system. The original set of requirements was developed through a process of conducting a user-based survey of requirements for the simulation capability, coupled with an analysismore » of similar development efforts. The user-based approach ensured that existing concerns with respect to interoperability within the law enforcement community would be addressed. Law enforcement agencies within the designated pilot area of Cochise County, Arizona, were surveyed using interviews and ride-alongs during actual operations. The results of this survey were then accumulated, organized, and validated with the agencies to ensure the accuracy of the results. These requirements were then supplemented by adapting operational requirements from existing systems to ensure system reliability and operability. The NCC adopted a development approach providing incremental capability through the fielding of a phased series of progressively more capable versions of the system. This allowed for feedback from system users to be incorporated into subsequent revisions of the system requirements, and also allowed the addition of new elements as needed to adapt the system to broader geographic and geopolitical areas, including areas along the southwest and northwest U.S. borders. This paper addresses the processes used to develop and refine requirements for the NCC interoperability simulation capability, as well as the response of the law enforcement community to the use of the NCC system. The paper also addresses the applicability of such an interoperability simulation capability to a broader set of law enforcement, border protection, site/facility security, and first-responder needs.« less

Integrating supply and demand aspects of transportation for mass evacuation under disasters.

DOT National Transportation Integrated Search

2009-10-15

This study seeks to address real-time operational needs in the context of the evacuation response problem by providing a capability to dynamically route vehicles under evacuation, thereby being responsive to the actual conditions unfolding in real-ti...

Computational Modeling in Concert with Laboratory Studies: Application to B Cell Differentiation

EPA Science Inventory

Remediation is expensive, so accurate prediction of dose-response is important to help control costs. Dose response is a function of biological mechanisms. Computational models of these mechanisms improve the efficiency of research and provide the capability for prediction.

Leadership capabilities of physiotherapy leaders in Ireland: Part 2. Clinical specialists and advanced physiotherapy practitioners.

PubMed

McGowan, E; Elliott, N; Stokes, E

2018-05-07

Investigation of the leadership capabilities of physiotherapy managers found that they report predominantly demonstrating capabilities associated with the human resource and structural frames. However, little is known about the leadership capabilities of clinical specialists and advanced physiotherapy practitioners (APPs) who also are identified as having responsibility for leadership. To explore clinical specialists´ and APPs' perceptions of their leadership capabilities and compare them with the reported leadership capabilities of physiotherapy managers. Semi-structured interviews were conducted with a purposive sample of 17 physiotherapy clinical specialists and APPs from a range of practice settings across Ireland. The interviews were analyzed using template analysis and the coding template was based on the Bolman and Deal Leadership framework. The participants described demonstrating leadership capabilities associated with each of the four leadership frames. However, the language used by the clinical specialists/APPs suggested that they work predominantly through the human resource frame. Structural frame capabilities were reported by the clinical specialists/APPs and there were some differences to those reported by the managers. In keeping with the reported leadership capabilities of the physiotherapy managers, the employment of capabilities associated with the political frame varied between participants and symbolic frame capabilities were underused. There are many similarities in the self-reported leadership capabilities of managers and clinical specialists/APPs. However, differences were also noted. Both cohorts of physiotherapy leaders may benefit from specific development programs to develop leadership capabilities associated with the political and symbolic frames.

Robotic disaster recovery efforts with ad-hoc deployable cloud computing

NASA Astrophysics Data System (ADS)

Straub, Jeremy; Marsh, Ronald; Mohammad, Atif F.

2013-06-01

Autonomous operations of search and rescue (SaR) robots is an ill posed problem, which is complexified by the dynamic disaster recovery environment. In a typical SaR response scenario, responder robots will require different levels of processing capabilities during various parts of the response effort and will need to utilize multiple algorithms. Placing these capabilities onboard the robot is a mediocre solution that precludes algorithm specific performance optimization and results in mediocre performance. Architecture for an ad-hoc, deployable cloud environment suitable for use in a disaster response scenario is presented. Under this model, each service provider is optimized for the task and maintains a database of situation-relevant information. This service-oriented architecture (SOA 3.0) compliant framework also serves as an example of the efficient use of SOA 3.0 in an actual cloud application.

Prevention of duodenal ileus reveals functional differences in the duodenal response to luminal hypertonicity in Sprague-Dawley and Dark Agouti rats.

PubMed

Sedin, J; Sjöblom, M; Nylander, O

2014-03-01

The mechanism by which the duodenum adjusts the luminal osmolality remains unclear. The aim was to compare the duodenal osmoregulation in response to different hyperosmolar solutions in Sprague-Dawley and Dark Agouti rats and to elucidate whether cyclooxygenase-2 inhibition affects these responses. The duodenum was perfused in situ with a 700-milliosmolar solution (NaCl alone, D-glucose ± NaCl, D-mannitol ± NaCl or orange juice), and the effects on the duodenal motility, mucosal permeability, luminal alkalinization, fluid flux and osmoregulation were assessed in anaesthetized rats. The change in net fluid flux and luminal osmolality, in response to a given hyperosmolar solution, was almost identical in control rats of both strains. In control rats, hypertonic D-glucose-NaCl induced fluid secretion only in the presence of phlorizin, an inhibitor of SGLT1. Cyclooxygenase-2 inhibition potentiated the hypertonicity-induced fluid secretion and increased the osmolality-adjusting capability in both strains, but the responses were greater in Dark Agouti rats. While cyclooxygenase-2-inhibited Dark Agouti rats responded to the hyperosmolar solutions with depression of motility and increased mucosal permeability, these effects were absent or smaller in the Sprague-Dawley strain. In contrast, orange juice induced the same duodenal responses in cyclooxygenase-2-inhibited Dark Agouti and Sprague-Dawley rats. The duodenum possesses the ability to absorb fluid despite a very high luminal osmolality. Inhibition of cyclooxygenase-2 markedly enhanced the capability of the duodenum to secrete fluid and to decrease luminal osmolality, irrespective of the hyperosmolar solution or the rat strain used, and revealed notable differences between the two strains with regard to their osmolality-adjusting capability. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Quantifying the plant actin cytoskeleton response to applied pressure using nanoindentation.

PubMed

Branco, Rémi; Pearsall, Eliza-Jane; Rundle, Chelsea A; White, Rosemary G; Bradby, Jodie E; Hardham, Adrienne R

2017-03-01

Detection of potentially pathogenic microbes through recognition by plants and animals of both physical and chemical signals associated with the pathogens is vital for host well-being. Signal perception leads to the induction of a variety of responses that augment pre-existing, constitutive defences. The plant cell wall is a highly effective preformed barrier which becomes locally reinforced at the infection site through delivery of new wall material by the actin cytoskeleton. Although mechanical stimulation can produce a reaction, there is little understanding of the nature of physical factors capable of triggering plant defence. Neither the magnitude of forces nor the contact time required has been quantified. In the study reported here, mechanical stimulation with a tungsten microneedle has been used to quantify the response of Arabidopsis plants expressing an actin-binding protein tagged with green fluorescent protein (GFP) to reveal the organisation of the actin cytoskeleton. Using confocal microscopy, the response time for actin reorganisation in epidermal cells of Arabidopsis hypocotyls was shown to be 116 ± 49 s. Using nanoindentation and a diamond spherical tip indenter, the magnitude of the forces capable of triggering an actin response has been quantified. We show that Arabidopsis hypocotyl cells can detect a force as small as 4 μN applied for as short a time as 21.6 s to trigger reorganisation of the actin cytoskeleton. This force is an order of magnitude less than the potential invasive force determined for a range of fungal and oomycete plant pathogens. To our knowledge, this is the first quantification of the magnitude and duration of mechanical forces capable of stimulating a structural defence response in a plant cell.

Electrocatalytic tuning of biosensing response through electrostatic or hydrophobic enzyme-graphene oxide interactions.

PubMed

Baptista-Pires, Luis; Pérez-López, Briza; Mayorga-Martinez, Carmen C; Morales-Narváez, Eden; Domingo, Neus; Esplandiu, Maria Jose; Alzina, Francesc; Sotomayor-Torres, Clivia M; Merkoçi, Arben

2014-11-15

The effect of graphene oxidative grades upon the conductivity and hydrophobicity and consequently the influence on an enzymatic biosensing response is presented. The electrochemical responses of reduced graphene oxide (rGO) have been compared with the responses obtained from the oxide form (oGO) and their performances have been accordingly discussed with various evidences obtained by optical techniques. We used tyrosinase enzyme as a proof of concept receptor with interest for phenolic compounds detection through its direct adsorption onto a screen-printed carbon electrode previously modified with oGO or rGO with a carbon-oxygen ratio of 1.07 or 1.53 respectively. Different levels of oGO directly affect the (bio)conjugation properties of the biosensor due to changes at enzyme/graphene oxide interface coming from the various electrostatic or hydrophobic interactions with biomolecules. The developed biosensor was capable of reaching a limit of detection of 0.01 nM catechol. This tuning capability of the biosensor response can be of interest for building several other biosensors, including immunosensors and DNA sensors for various applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Field Experience with and Potential for Multi-time Scale Grid Transactions from Responsive Commercial Buildings

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

Piette, Mary Ann; Kiliccote, Sila; Ghatikar, Girish

2014-08-01

The need for and concepts behind demand response are evolving. As the electric system changes with more intermittent renewable electric supply systems, there is a need to allow buildings to provide more flexible demand. This paper presents results from field studies and pilots, as well as engineering estimates of the potential capabilities of fast load responsiveness in commercial buildings. We present a sector wide analysis of flexible loads in commercial buildings, which was conducted to improve resource planning and determine which loads to evaluate in future demonstrations. These systems provide important capabilities for future transactional systems. The field analysis ismore » based on results from California, plus projects in the northwest and east coast. End-uses considered include heating, ventilation, air conditioning and lighting. The timescales of control include day-ahead, as well as day-of, 10-minute ahead and even faster response. This technology can provide DR signals on different times scales to interact with responsive building loads. We describe the latency of the control systems in the building and the round trip communications with the wholesale grid operators.« less

Community Assessment for Public Health Emergency Response (CASPER): An Innovative Emergency Management Tool in the United States.

PubMed

Schnall, Amy; Nakata, Nicole; Talbert, Todd; Bayleyegn, Tesfaye; Martinez, DeAndrea; Wolkin, Amy

2017-09-01

To demonstrate how inclusion of the Centers for Disease Control and Prevention's Community Assessment for Public Health Emergency Response (CASPER) as a tool in Public Health Preparedness Capabilities: National Standards for State and Local Planning can increase public health capacity for emergency response. We reviewed all domestic CASPER activities (i.e., trainings and assessments) between fiscal years 2012 and 2016. Data from these CASPER activities were compared with respect to differences in geographic distribution, type, actions, efficacy, and usefulness of training. During the study period, the Centers for Disease Control and Prevention conducted 24 domestic in-person CASPER trainings for 1057 staff in 38 states. On average, there was a marked increase in knowledge of CASPER. Ninety-nine CASPERs were conducted in the United States, approximately half of which (53.5%) assessed preparedness; the others were categorized as response or recovery (27.2%) or were unrelated to a disaster (19.2%). CASPER trainings are successful in increasing disaster epidemiology skills. CASPER can be used by Public Health Emergency Preparedness program awardees to help build and sustain preparedness and response capabilities.

3'-Azido-2',3'-dideoxythymidine induced deficiency of thymidine kinases 1, 2 and deoxycytidine kinase in H9 T-lymphoid cells.

PubMed

Gröschel, Bettina; Kaufmann, Andreas; Höver, Gerold; Cinatl, Jaroslav; Doerr, Hans Wilhelm; Noordhuis, Paul; Loves, Willem J P; Peters, Godefridus J; Cinatl, Jindrich

2002-07-15

Continuous cultivation of T-lymphoid H9 cells in the presence of 3'-azido-2',3'-dideoxythymidine (AZT) resulted in a cell variant cross-resistant to both thymidine and deoxycytidine analogs. Cytotoxic effects of AZT, 2',3'-didehydro-3'-deoxythymidine as well as different deoxycytidine analogs such as 2',3'-dideoxycytidine, 2',2'-difluoro-2'-deoxycytidine (dFdC) and 1-ss-D-arabinofuranosylcytosine (Ara-C) were strongly reduced in H9 cells continuously exposed to AZT when compared to parental cells (>8.3-, >6.6-, >9.1-, 5 x 10(4)-, 5 x 10(3)-fold, respectively). Moreover, anti-HIV-1 effects of AZT, d4T, ddC and 2',3'-dideoxy-3'-thiacytidine (3TC) were significantly diminished (>222-, >25-, >400-, >200-fold, respectively) in AZT-resistant H9 cells. Study of cellular mechanisms responsible for cross-resistance to pyrimidine analogs in AZT-resistant H9 cells revealed decreased mRNA levels of thymidine kinase 1 (TK1) and lack of deoxycytidine kinase (dCK) mRNA expression. The loss of dCK gene expression was confirmed by western blot analysis of dCK protein as well as dCK enzyme activity assay. Moreover, enzyme activity of TK1 and TK2 was reduced in AZT-resistant cells. In order to determine whether lack of dCK affected the formation of the active triphosphate of the deoxycytidine analog dFdC, dFdCTP accumulation and retention was measured in H9 parental and AZT-resistant cells after exposure to 1 and 10 microM dFdC. Parental H9 cells accumulated about 30 and 100 pmol dFdCTP/10(6) cells after 4hr, whereas in AZT-resistant cells no dFdCTP accumulation was detected. These results demonstrate that continuous treatment of H9 cells in the presence of AZT selected for a thymidine analog resistant cell variant with cross-resistance to deoxycytidine analogs, due to deficiency in TK1, TK2, and dCK.

MINIS: Multipurpose Interactive NASA Information System

NASA Technical Reports Server (NTRS)

1976-01-01

The Multipurpose Interactive NASA Information Systems (MINIS) was developed in response to the need for a data management system capable of operation on several different minicomputer systems. The desired system had to be capable of performing the functions of a LANDSAT photo descriptive data retrieval system while remaining general in terms of other acceptable user definable data bases. The system also had to be capable of performing data base updates and providing user-formatted output reports. The resultant MINI System provides all of these capabilities and several other features to complement the data management system. The MINI System is currently implemented on two minicomputer systems and is in the process of being installed on another minicomputer system. The MINIS is operational on four different data bases.

National Labs and Nuclear Emergency Response

NASA Astrophysics Data System (ADS)

Budil, Kimberly

2015-04-01

The DOE national laboratories, and in particular the three NNSA national security laboratories, have long supported a broad suite of national nuclear security missions for the U.S. government. The capabilities, infrastructure and base of expertise developed to support the U.S. nuclear weapons stockpile have been applied to such challenges as stemming nuclear proliferation, understanding the nuclear capabilities of adversaries, and assessing and countering nuclear threats including essential support to nuclear emergency response. This talk will discuss the programs that are underway at the laboratories and the essential role that science and technology plays therein. Nuclear scientists provide expertise, fundamental understanding of nuclear materials, processes and signatures, and tools and technologies to aid in the identification and mitigation of nuclear threats as well as consequence management. This talk will also discuss the importance of direct engagement with the response community, which helps to shape research priorities and to enable development of useful tools and techniques for responders working in the field. National Labs and Nuclear Emergency Response.

Emergency drinking water treatment during source water pollution accidents in China: origin analysis, framework and technologies.

PubMed

Zhang, Xiao-Jian; Chen, Chao; Lin, Peng-Fei; Hou, Ai-Xin; Niu, Zhang-Bin; Wang, Jun

2011-01-01

China has suffered frequent source water contamination accidents in the past decade, which has resulted in severe consequences to the water supply of millions of residents. The origins of typical cases of contamination are discussed in this paper as well as the emergency response to these accidents. In general, excessive pursuit of rapid industrialization and the unreasonable location of factories are responsible for the increasing frequency of accidental pollution events. Moreover, insufficient attention to environmental protection and rudimentary emergency response capability has exacerbated the consequences of such accidents. These environmental accidents triggered or accelerated the promulgation of stricter environmental protection policy and the shift from economic development mode to a more sustainable direction, which should be regarded as the turning point of environmental protection in China. To guarantee water security, China is trying to establish a rapid and effective emergency response framework, build up the capability of early accident detection, and develop efficient technologies to remove contaminants from water.

Oil spill response capabilities and technologies for ice-covered Arctic marine waters: A review of recent developments and established practices.

PubMed

Wilkinson, Jeremy; Beegle-Krause, C J; Evers, Karl-Ulrich; Hughes, Nick; Lewis, Alun; Reed, Mark; Wadhams, Peter

2017-12-01

Renewed political and commercial interest in the resources of the Arctic, the reduction in the extent and thickness of sea ice, and the recent failings that led to the Deepwater Horizon oil spill, have prompted industry and its regulatory agencies, governments, local communities and NGOs to look at all aspects of Arctic oil spill countermeasures with fresh eyes. This paper provides an overview of present oil spill response capabilities and technologies for ice-covered waters, as well as under potential future conditions driven by a changing climate. Though not an exhaustive review, we provide the key research results for oil spill response from knowledge accumulated over many decades, including significant review papers that have been prepared as well as results from recent laboratory tests, field programmes and modelling work. The three main areas covered by the review are as follows: oil weathering and modelling; oil detection and monitoring; and oil spill response techniques.

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses.The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses. The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

Roles of inter-SWCNT junctions in resistive humidity response

NASA Astrophysics Data System (ADS)

Zhang, Kang; Zou, Jianping; Zhang, Qing

2015-11-01

As a promising chemiresistor for gas sensing, the single-walled carbon nanotube (SWCNT) network has not yet been fully utilized for humidity detection. In this work, it is found that as humidity increases from 10% to 85%, the resistance of as-grown SWCNT networks first decreases and then increases. This non-monotonic resistive response to humidity limits their sensing capabilities. The competition between SWCNT resistance and inter-tube junction resistance changes is then found to be responsible for the non-monotonic resistive humidity responses. Moreover, creating sp3 scattering centers on the SWCNT sidewall by monovalent functionalization of four-bromobenzene diazonium tetrafluoroborate is shown to be capable of eliminating the influence from the inter-tube junctions, resulting in a continuous resistance drop as humidity increases from 10% to 85%. Our results revealed the competing resistive humidity sensing process in as-grown SWCNT networks, which could also be helpful in designing and optimizing as-grown SWCNT networks for humidity sensors and other gas sensors.

The Army and the Need for an Amphibious Capability

DTIC Science & Technology

2015-05-23

prevailing Army-Marine amphibious set-up was unsound because only the Army had both the means and the grasp of the problem to plan, prepare, and... The Army and the Need for an Amphibious Capability A Monograph by MAJ Joseph E. Malone United States Army...this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data

Cloud-Based Numerical Weather Prediction for Near Real-Time Forecasting and Disaster Response

NASA Technical Reports Server (NTRS)

Molthan, Andrew; Case, Jonathan; Venner, Jason; Schroeder, Richard; Checchi, Milton; Zavodsky, Bradley; O'Brien, Raymond

2015-01-01

Cloud computing capabilities have rapidly expanded within the private sector, offering new opportunities for meteorological applications. Collaborations between NASA Marshall, NASA Ames, and contractor partners led to evaluations of private (NASA) and public (Amazon) resources for executing short-term NWP systems. Activities helped the Marshall team further understand cloud capabilities, and benchmark use of cloud resources for NWP and other applications

Enhanced Rescue Lift Capability

NASA Technical Reports Server (NTRS)

Young, Larry A.

2007-01-01

The evolving and ever-increasing demands of emergency response and disaster relief support provided by rotorcraft dictate, among other things, the development of enhanced rescue lift capability for these platforms. This preliminary analysis is first-order in nature but provides considerable insight into some of the challenges inherent in trying to effect rescue using a unique form of robotic rescue device deployed and operated from rotary-wing aerial platforms.

Building Core Capabilities for Life: The Science behind the Skills Adults Need to Succeed in Parenting and in the Workplace

ERIC Educational Resources Information Center

Center on the Developing Child at Harvard University, 2016

2016-01-01

Adults need certain capabilities to get and keep a job, provide responsive care for children, manage a household, and contribute productively to the community. When these skills have not developed as they should, or are compromised by the stresses of poverty or other ongoing adversity, our communities pay the price. But where do these capabilities…

Developing Soft Power Using Afloat Medical Capability

DTIC Science & Technology

2009-03-02

the National Security Strategy. Depending on its program employment , it has the capability to effectively combine the other elements of national power...Strategy through the employment of combatant commanders’ Theater Security Cooperation (TSC) Program in their area of responsibility. The TSC program is...In the final phases of Pacific campaign during World War II, tactical doctrine for employment of Navy hospital vessels changed, allowing them to

NASA's Dual-Fuel Airbreathing Hypersonic Vehicle Study

NASA Technical Reports Server (NTRS)

Hunt, James L.; Eiswirth, Edward A.

1996-01-01

A Mach 10 cruise vehicle provides a quick response, global reach capability with high survivability. For operations from CONUS, mission radii on the order of 8,000 nmi are sufficient. For missions which return to CONUS, a dual-fueled vehicle is superior, due to its capability to in-flight refuel. However, for one-way mission, an all-hydrogen vehicle is preferable because of its higher specific impulse.

Maritime Homeland Command Control: Teaching an Old Dog New Tricks

DTIC Science & Technology

2002-02-04

Security, Command and Control, Navy, Coast Guard, Customs Service, Centralized Control, Decentralized Execution, Organization by Objectives 15.Abstract...primarily responsible for the maritime homeland, the Navy, the Coast guard, the Customs Service, should provide resources and command capabilities to a...Coast Guard, the Customs Service, should provide resources and command capabilities to a unified command and control structure. Coast Guard forces and

Lipid Multilayer Grating Arrays Integrated by Nanointaglio for Vapor Sensing by an Optical Nose

PubMed Central

Lowry, Troy W.; Prommapan, Plengchart; Rainer, Quinn; Van Winkle, David; Lenhert, Steven

2015-01-01

Lipid multilayer gratings are recently invented nanomechanical sensor elements that are capable of transducing molecular binding to fluid lipid multilayers into optical signals in a label free manner due to shape changes in the lipid nanostructures. Here, we show that nanointaglio is suitable for the integration of chemically different lipid multilayer gratings into a sensor array capable of distinguishing vapors by means of an optical nose. Sensor arrays composed of six different lipid formulations are integrated onto a surface and their optical response to three different vapors (water, ethanol and acetone) in air as well as pH under water is monitored as a function of time. Principal component analysis of the array response results in distinct clustering indicating the suitability of the arrays for distinguishing these analytes. Importantly, the nanointaglio process used here is capable of producing lipid gratings out of different materials with sufficiently uniform heights for the fabrication of an optical nose. PMID:26308001

Maintaining Situation Awareness with Autonomous Airborne Observation Platforms

NASA Technical Reports Server (NTRS)

Freed, Michael; Fitzgerald, Will

2005-01-01

Unmanned Aerial Vehicles (UAVs) offer tremendous potential as intelligence, surveillance and reconnaissance (ISR) platforms for early detection of security threats and for acquisition and maintenance of situation awareness in crisis conditions. However, using their capabilities effectively requires addressing a range of practical and theoretical problems. The paper will describe progress by the "Autonomous Rotorcraft Project," a collaborative effort between NASA and the U.S. Army to develop a practical, flexible capability for UAV-based ISR. Important facets of the project include optimization methods for allocating scarce aircraft resources to observe numerous, distinct sites of interest; intelligent flight automation software than integrates high-level plan generation capabilities with executive control, failure response and flight control functions; a system architecture supporting reconfiguration of onboard sensors to address different kinds of threats; and an advanced prototype vehicle designed to allow large-scale production at low cost. The paper will also address human interaction issues including an empirical method for determining how to allocate roles and responsibilities between flight automation and human operations.

DAMIC at SNOLAB

DOE PAGES

Chavarria, Alvaro E.; Tiffenberg, Javier; Aguilar-Arevalo, Alexis; ...

2015-03-24

We introduce the fully-depleted charge-coupled device (CCD) as a particle detector. We demonstrate its low energy threshold operation, capable of detecting ionizing energy depositions in a single pixel down to 50 eV ee. We present results of energy calibrations from 0.3 keV ee to 60 ke Vee, showing that the CCD is a fully active detector with uniform energy response throughout the silicon target, good resolution (Fano ~0.16), and remarkable linear response to electron energy depositions. We show the capability of the CCD to localize the depth of particle interactions within the silicon target. We discuss the mode of operationmore » and unique imaging capabilities of the CCD, and how they may be exploited to characterize and suppress backgrounds. We present the first results from the deployment of 250 μm thick CCDs in SNOLAB, a prototype for the upcoming DAMIC100. DAMIC100 will have a target mass of 0.1 kg and should be able to directly test the CDMS-Si signal within a year of operation.« less

On the formal definition of the systems' interoperability capability: an anthropomorphic approach

NASA Astrophysics Data System (ADS)

Zdravković, Milan; Luis-Ferreira, Fernando; Jardim-Goncalves, Ricardo; Trajanović, Miroslav

2017-03-01

The extended view of enterprise information systems in the Internet of Things (IoT) introduces additional complexity to the interoperability problems. In response to this, the problem of systems' interoperability is revisited by taking into the account the different aspects of philosophy, psychology, linguistics and artificial intelligence, namely by analysing the potential analogies between the processes of human and system communication. Then, the capability to interoperate as a property of the system, is defined as a complex ability to seamlessly sense and perceive a stimulus from its environment (assumingly, a message from any other system), make an informed decision about this perception and consequently, articulate a meaningful and useful action or response, based on this decision. Although this capability is defined on the basis of the existing interoperability theories, the proposed approach to its definition excludes the assumption on the awareness of co-existence of two interoperating systems. Thus, it establishes the links between the research of interoperability of systems and intelligent software agents, as one of the systems' digital identities.

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

Andrews, Madison Theresa; Bates, Cameron Russell; Mckigney, Edward Allen

Here, this work presents the organic scintillation simulation capabilities of DRiFT, a post-processing Detector Response Function Toolkit for MCNPR output. DRiFT is used to create realistic scintillation detector response functions to incident neutron and gamma mixed- field radiation. As a post-processing tool, DRiFT leverages the extensively validated radiation transport capabilities of MCNPR ®6, which also provides the ability to simulate complex sources and geometries. DRiFT is designed to be flexible, it allows the user to specify scintillator material, PMT type, applied PMT voltage, and quenching data used in simulations. The toolkit's capabilities, which include the generation of pulse shape discriminationmore » plots and full-energy detector spectra, are demonstrated in a comparison of measured and simulated neutron contributions from 252Cf and PuBe, and photon spectra from 22Na and 228Th sources. DRiFT reproduced energy resolution effects observed in EJ-301 measurements through the inclusion of scintillation yield variances, photon transport noise, and PMT photocathode and multiplication noise.« less

Development of a computer model for prediction of collision response of a railroad passenger car

DOT National Transportation Integrated Search

2002-04-23

The paper describes the development of a detailed finite element model that is capable of predicting the response of a rail passenger car to collision conditions. This model was developed to predict the car crush, the three-dimensional gross motions ...

Responsive and Proactive Stakeholder Orientation in Public Universities: Antecedents and Consequences

ERIC Educational Resources Information Center

Alarcón-del-Amo, María-del-Carmen; Casablancas-Segura, Carme; Llonch, Joan

2016-01-01

This study, based on institutional theory, dynamic capabilities, and stakeholder theory, investigates the relationships between the antecedents of responsive and proactive stakeholder orientation and their consequences in the public university context. The results obtained mainly stress that the mimetic effect of copying successful university…

The insect capa neuropeptides impact desiccation and cold stress responses

USDA-ARS?s Scientific Manuscript database

Background: Insects are so successful because of great resistance to environmental stress, yet little is known about how such responses may be mediated by the neuroendocrine system. Results: We provide evidence that the capability (capa) neuropeptide gene and peptide are critical mediators of desic...

Blockade of the dopamine depressor response by molindone, a newly introduced neuroleptic.

PubMed

Nandal, N V; Mane, V R; Balsara, J J; Chandorkar, A G

1980-01-01

Pretreatment with the neuroleptics, haloperidol and molindone, significantly antagonized the dopamine-induced depressor response in the anaesthetized dogs. The depressor response to dopamine was however, not significantly affected by propranolol, atropine or antazoline pretreatment. The results suggest that molindone like haloperidol, is capable of blocking the vascular dopamine receptors responsible for mediating dopamine-induced vasodilatation in the coeliac, mesenteric and renal vascular bed and fall in blood pressure.

Capability Investment Strategy to Enable JPL Future Space Missions

NASA Technical Reports Server (NTRS)

Lincoln, William; Merida, Sofia; Adumitroaie, Virgil; Weisbin, Charles R.

2006-01-01

The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future missions are ready as needed. The responsibilities include development of a Strategic Plan (Antonsson, E., 2005). As part of the planning effort, a structured approach to technology prioritization, based upon the work of the START (Strategic Assessment of Risk and Technology) (Weisbin, C.R., 2004) team, was developed. The purpose of this paper is to describe this approach and present its current status relative to the JPL technology investment.

Predictions of the electro-mechanical response of conductive CNT-polymer composites

NASA Astrophysics Data System (ADS)

Matos, Miguel A. S.; Tagarielli, Vito L.; Baiz-Villafranca, Pedro M.; Pinho, Silvestre T.

2018-05-01

We present finite element simulations to predict the conductivity, elastic response and strain-sensing capability of conductive composites comprising a polymeric matrix and carbon nanotubes. Realistic representative volume elements (RVE) of the microstructure are generated and both constituents are modelled as linear elastic solids, with resistivity independent of strain; the electrical contact between nanotubes is represented by a new element which accounts for quantum tunnelling effects and captures the sensitivity of conductivity to separation. Monte Carlo simulations are conducted and the sensitivity of the predictions to RVE size is explored. Predictions of modulus and conductivity are found in good agreement with published results. The strain-sensing capability of the material is explored for multiaxial strain states.

Aviation System Analysis Capability (ASAC) Quick Response System (QRS) Test Report

NASA Technical Reports Server (NTRS)

Roberts, Eileen; Villani, James A.; Ritter, Paul

1997-01-01

This document is the Aviation System Analysis Capability (ASAC) Quick Response System (QRS) Test Report. The purpose of this document is to present the results of the QRS unit and system tests in support of the ASAC QRS development effort. This document contains an overview of the project background and scope, defines the QRS system and presents the additions made to the QRS this year, explains the assumptions, constraints, and approach used to conduct QRS Unit and System Testing, and presents the schedule used to perform QRS Testing. The document also presents an overview of the Logistics Management Institute (LMI) Test Facility and testing environment and summarizes the QRS Unit and System Test effort and results.

Emergency Response Capability Baseline Needs Assessment Compliance Assessment

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

Sharry, John A.

2013-09-16

This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, firemore » department training records, and fire department policies and procedures.« less

Benefits of a European project on diagnostics of highly pathogenic agents and assessment of potential "dual use" issues.

PubMed

Grunow, Roland; Ippolito, G; Jacob, D; Sauer, U; Rohleder, A; Di Caro, A; Iacovino, R

2014-01-01

Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and "dual use" concerns. The article will give an overview of the project outcomes and discuss the assessment of potential "dual use" issues.

BEopt-CA (Ex) -- A Tool for Optimal Integration of EE/DR/ES+PV in Existing California Homes. Cooperative Research and Development Final Report, CRADA Number CRD-11-429

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

Christensen, Craig

Opportunities for combining energy efficiency, demand response, and energy storage with PV are often missed, because the required knowledge and expertise for these different technologies exist in separate organizations or individuals. Furthermore, there is a lack of quantitative tools to optimize energy efficiency, demand response and energy storage with PV, especially for existing buildings. Our goal is to develop a modeling tool, BEopt-CA (Ex), with capabilities to facilitate identification and implementation of a balanced integration of energy efficiency (EE), demand response (DR), and energy storage (ES) with photovoltaics (PV) within the residential retrofit market. To achieve this goal, we willmore » adapt and extend an existing tool -- BEopt -- that is designed to identify optimal combinations of efficiency and PV in new home designs. In addition, we will develop multifamily residential modeling capabilities for use in California, to facilitate integration of distributed solar power into the grid in order to maximize its value to California ratepayers. The project is follow-on research that leverages previous California Solar Initiative RD&D investment in the BEopt software. BEopt facilitates finding the least cost combination of energy efficiency and renewables to support integrated DSM (iDSM) and Zero Net Energy (ZNE) in California residential buildings. However, BEopt is currently focused on modeling single-family houses and does not include satisfactory capabilities for modeling multifamily homes. The project brings BEopt's existing modeling and optimization capabilities to multifamily buildings, including duplexes, triplexes, townhouses, flats, and low-rise apartment buildings.« less

Benefits of a European Project on Diagnostics of Highly Pathogenic Agents and Assessment of Potential “Dual Use” Issues

PubMed Central

Grunow, Roland; Ippolito, G.; Jacob, D.; Sauer, U.; Rohleder, A.; Di Caro, A.; Iacovino, R.

2014-01-01

Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and “dual use” concerns. The article will give an overview of the project outcomes and discuss the assessment of potential “dual use” issues. PMID:25426479

Induction of Both Local Immune Response in Mice and Protection in a Rabbit Model by Intranasal Immunization with Modified Vaccinia Ankara Virus Expressing a Secreted Form of Bovine Herpesvirus 1 Glycoprotein D.

PubMed

Del Medico Zajac, María Paula; Zanetti, Flavia Adriana; Esusy, María Soledad; Federico, Carlos Rodolfo; Zabal, Osvaldo; Valera, Alejandro Rafael; Calamante, Gabriela

In this study, we evaluated the immunogenicity and efficacy of mucosal delivery of a recombinant modified vaccinia Ankara virus (MVA) expressing the secreted version of bovine herpesvirus type 1 (BoHV-1) glycoprotein D (MVA-gDs) without addition of adjuvant in two animal models. First, we demonstrated the capability of MVA-gDs of inducing both local and systemic anti-gD humoral immune response after intranasal immunization of mice. Then, we confirmed that two doses of MVA-gDs administered intranasally to rabbits induced systemic anti-gD antibodies and conferred protection against BoHV-1 challenge. Our results show the potential of using MVA as a vector for the rational design of veterinary vaccines capable of inducing specific and protective immune responses both at local and systemic level.

Modeling a Civil Event Case Study for Consequence Management Using the IMPRINT Forces Module

NASA Technical Reports Server (NTRS)

Gacy, Marc; Gosakan, Mala; Eckdahl, Angela; Miller, Jeffrey R.

2012-01-01

A critical challenge in the Consequence Management (CM) domain is the appropriate allocation of necessary and skilled military and civilian personnel and materiel resources in unexpected emergencies. To aid this process we used the Forces module in the Improved Performance Research Integration Tool (IMPRINT). This module enables analysts to enter personnel and equipment capabilities, prioritized schedules and numbers available, along with unexpected emergency requirements in order to assess force response requirements. Using a suspected terrorist threat on a college campus, we developed a test case model which exercised the capabilities of the module, including the scope and scale of operations. The model incorporates data from multiple sources, including daily schedules and frequency of events such as fire calls. Our preliminary results indicate that the model can predict potential decreases in civilian emergency response coverage due to an involved unplanned incident requiring significant portions of police, fire and civil responses teams.

Spatial Frequency Responses of Anisotropic Refractive Index Gratings Formed in Holographic Polymer Dispersed Liquid Crystals

PubMed Central

Fukuda, Yoshiaki; Tomita, Yasuo

2016-01-01

We report on an experimental investigation of spatial frequency responses of anisotropic transmission refractive index gratings formed in holographic polymer dispersed liquid crystals (HPDLCs). We studied two different types of HPDLC materials employing two different monomer systems: one with acrylate monomer capable of radical mediated chain-growth polymerizations and the other with thiol-ene monomer capable of step-growth polymerizations. It was found that the photopolymerization kinetics of the two HPDLC materials could be well explained by the autocatalytic model. We also measured grating-spacing dependences of anisotropic refractive index gratings at a recording wavelength of 532 nm. It was found that the HPDLC material with the thiol-ene monomer gave higher spatial frequency responses than that with the acrylate monomer. Statistical thermodynamic simulation suggested that such a spatial frequency dependence was attributed primarily to a difference in the size of formed liquid crystal droplets due to different photopolymerization mechanisms. PMID:28773314

Spatial Frequency Responses of Anisotropic Refractive Index Gratings Formed in Holographic Polymer Dispersed Liquid Crystals.

PubMed

Fukuda, Yoshiaki; Tomita, Yasuo

2016-03-10

We report on an experimental investigation of spatial frequency responses of anisotropic transmission refractive index gratings formed in holographic polymer dispersed liquid crystals (HPDLCs). We studied two different types of HPDLC materials employing two different monomer systems: one with acrylate monomer capable of radical mediated chain-growth polymerizations and the other with thiol-ene monomer capable of step-growth polymerizations. It was found that the photopolymerization kinetics of the two HPDLC materials could be well explained by the autocatalytic model. We also measured grating-spacing dependences of anisotropic refractive index gratings at a recording wavelength of 532 nm. It was found that the HPDLC material with the thiol-ene monomer gave higher spatial frequency responses than that with the acrylate monomer. Statistical thermodynamic simulation suggested that such a spatial frequency dependence was attributed primarily to a difference in the size of formed liquid crystal droplets due to different photopolymerization mechanisms.

Stennis Space Center Verification and Validation Capabilities

NASA Technical Reports Server (NTRS)

O'Neal, Duane; Daehler, Erik

2006-01-01

Topics covered include: Spatial Response; Reflectance Radiometry; Positional Accuracy; Stationary Atmospheric Monitoring; Laboratory Calibration; Thermal Radiometry; Hyperspectral Radiometry; and Portable Atmospheric Monitoring.

Autonomic nervous system response patterns specificity to basic emotions.

PubMed

Collet, C; Vernet-Maury, E; Delhomme, G; Dittmar, A

1997-01-12

The aim of this study was to test the assumption that the autonomic nervous system responses to emotional stimuli are specific. A series of six slides was randomly presented to the subjects while six autonomic nervous system (ANS) parameters were recorded: skin conductance, skin potential, skin resistance, skin blood flow, skin temperature and instantaneous respiratory frequency. Each slide induced a basic emotion: happiness, surprise, anger, fear, sadness and disgust. Results have been first considered with reference to electrodermal responses (EDR) and secondly through thermo-vascular and respiratory variations. Classical as well as original indices were used to quantify autonomic responses. The six basic emotions were distinguished by Friedman variance analysis. Thus, ANS values corresponding to each emotion were compared two-by-two. EDR distinguished 13 emotion-pairs out of 15. 10 emotion-pairs were separated by skin resistance as well as skin conductance ohmic perturbation duration indices whereas conductance amplitude was only capable of distinguishing 7 emotion-pairs. Skin potential responses distinguished surprise and fear from sadness, and fear from disgust, according to their elementary pattern analysis in form and sign. Two-by-two comparisons of skin temperature, skin blood flow (estimated by the new non-oscillary duration index) and instantaneous respiratory frequency, enabled the distinction of 14 emotion-pairs out of 15. 9 emotion-pairs were distinguished by the non-oscillatory duration index values. Skin temperature was demonstrated to be different i.e. positive versus negative in response to anger and fear. The instantaneous respiratory frequency perturbation duration index was the only one capable of separating sadness from disgust. From the six ANS parameters study, different autonomic patterns were identified, each characterizing one of the six basic emotion used as inducing signals. No index alone, nor group of parameters (EDR and thermovascular for instance) were capable of distinguishing each emotion from another. However, electrodermal, thermo-vascular and respiratory responses taken as a whole, redundantly separated each emotion thus demonstrating the specificity of autonomic patterns.

Validation of foF2 and TEC Modeling During Geomagnetic Disturbed Times: Preliminary Outcomes of International Forum for Space Weather Modeling Capabilities Assessment

NASA Astrophysics Data System (ADS)

Shim, J. S.; Tsagouri, I.; Goncharenko, L. P.; Kuznetsova, M. M.

2017-12-01

To address challenges of assessment of space weather modeling capabilities, the CCMC (Community Coordinated Modeling Center) is leading the newly established "International Forum for Space Weather Modeling Capabilities Assessment." This presentation will focus on preliminary outcomes of the International Forum on validation of modeled foF2 and TEC during geomagnetic storms. We investigate the ionospheric response to 2013 Mar. geomagnetic storm event using ionosonde and GPS TEC observations in North American and European sectors. To quantify storm impacts on foF2 and TEC, we first quantify quiet-time variations of foF2 and TEC (e.g., the median and the average of the five quietest days for the 30 days during quiet conditions). It appears that the quiet time variation of foF2 and TEC are about 10% and 20-30%, respectively. Therefore, to quantify storm impact, we focus on foF2 and TEC changes during the storm main phase larger than 20% and 50%, respectively, compared to 30-day median. We find that in European sector, both foF2 and TEC response to the storm are mainly positive phase with foF2 increase of up to 100% and TEC increase of 150%. In North America sector, however, foF2 shows negative effects (up to about 50% decrease), while TEC shows positive response (the largest increase is about 200%). To assess modeling capability of reproducing the changes of foF2 and TEC due to the storm, we use various model simulations, which are obtained from empirical, physics-based, and data assimilation models. The performance of each model depends on the selected metrics, therefore, only one metrics is not enough to evaluate the models' predictive capabilities in capturing the storm impact. The performance of the model also varies with latitude and longitude.

Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT

NASA Astrophysics Data System (ADS)

Jung, Yookyung; Klein, Oliver J.; Wang, Hequn; Evans, Conor L.

2016-06-01

Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.

Library of Advanced Materials for Engineering (LAME) 4.44.

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

Scherzinger, William M.; Lester, Brian T.

Accurate and efficient constitutive modeling remains a cornerstone issues for solid mechanics analysis. Over the years, the LAME advanced material model library has grown to address this challenge by implementing models capable of describing material systems spanning soft polymers to s ti ff ceramics including both isotropic and anisotropic responses. Inelastic behaviors including (visco) plasticity, damage, and fracture have all incorporated for use in various analyses. This multitude of options and flexibility, however, comes at the cost of many capabilities, features, and responses and the ensuing complexity in the resulting implementation. Therefore, to enhance confidence and enable the utilization ofmore » the LAME library in application, this effort seeks to document and verify the various models in the LAME library. Specifically, the broader strategy, organization, and interface of the library itself is first presented. The physical theory, numerical implementation, and user guide for a large set of models is then discussed. Importantly, a number of verification tests are performed with each model to not only have confidence in the model itself but also highlight some important response characteristics and features that may be of interest to end-users. Finally, in looking ahead to the future, approaches to add material models to this library and further expand the capabilities are presented.« less

Multiresponsive Kinematics and Robotics of Surface-Patterned Polymer Film.

PubMed

Liang, Shumin; Qiu, Xiaxin; Yuan, Jun; Huang, Wei; Du, Xuemin; Zhang, Lidong

2018-06-06

Soft robots, sensors, and energy harvesters require materials that are capable of converting external stimuli to visible deformations, especially when shape-programmable deformations are desired. Herein, we develop a polymer film that can reversibly respond to humidity, heating, and acetone vapors with the generation of shape-programmable large deformations. Poly(vinylidene fluoride) film, capable of providing acetone responsiveness, is designed with microchannel patterns created on its one side by using templates, and the microchannels-patterned side is then treated with hygroscopic 3-aminopropyltriethoxysilane (APTES) to give humidity/heating-responsive elements. The APTES-modified microchannels lead to anisotropic flexural modulus and hygroscopicity in the film, resulting in the shape-programmed kinematics depending on the orientations of surface microchannels. As the microchannels align at oblique/right angles with respect to the long axis of the film strips, the coiling/curling motions can be generated in response to the stimuli, and the better motion performances are found in humidity- and heating-driven systems. This material utilized in self-adaptive soft robots exhibits prominent toughness, powerful strength, and long endurance for converting humidity and heat to mechanical works including transportation of lightweight objects, automatic sensing cap, and mimicking crawling in nature. We thus believe that this material with shape-programmable multisensing capability might be suitable for soft machines and robotics.

Library of Advanced Materials for Engineering (LAME) 4.48.

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

Scherzinger, William M.; Lester, Brian T.

Accurate and efficient constitutive modeling remains a cornerstone issues for solid mechanics analysis. Over the years, the LAME advanced material model library has grown to address this challenge by implement- ing models capable of describing material systems spanning soft polymers to stiff ceramics including both isotropic and anisotropic responses. Inelastic behaviors including (visco)plasticity, damage, and fracture have all incorporated for use in various analyses. This multitude of options and flexibility, however, comes at the cost of many capabilities, features, and responses and the ensuing complexity in the resulting imple- mentation. Therefore, to enhance confidence and enable the utilization of themore » LAME library in application, this effort seeks to document and verify the various models in the LAME library. Specifically, the broader strategy, organization, and interface of the library itself is first presented. The physical theory, numerical implementation, and user guide for a large set of models is then discussed. Importantly, a number of verifi- cation tests are performed with each model to not only have confidence in the model itself but also highlight some important response characteristics and features that may be of interest to end-users. Finally, in looking ahead to the future, approaches to add material models to this library and further expand the capabilities are presented.« less

Rapid-Response Low Infrared Emission Broadband Ultrathin Plasmonic Light Absorber

PubMed Central

Tagliabue, Giulia; Eghlidi, Hadi; Poulikakos, Dimos

2014-01-01

Plasmonic nanostructures can significantly advance broadband visible-light absorption, with absorber thicknesses in the sub-wavelength regime, much thinner than conventional broadband coatings. Such absorbers have inherently very small heat capacity, hence a very rapid response time, and high light power-to-temperature sensitivity. Additionally, their surface emissivity can be spectrally tuned to suppress infrared thermal radiation. These capabilities make plasmonic absorbers promising candidates for fast light-to-heat applications, such as radiation sensors. Here we investigate the light-to-heat conversion properties of a metal-insulator-metal broadband plasmonic absorber, fabricated as a free-standing membrane. Using a fast IR camera, we show that the transient response of the absorber has a characteristic time below 13 ms, nearly one order of magnitude lower than a similar membrane coated with a commercial black spray. Concurrently, despite the small thickness, due to the large absorption capability, the achieved absorbed light power-to-temperature sensitivity is maintained at the level of a standard black spray. Finally, we show that while black spray has emissivity similar to a black body, the plasmonic absorber features a very low infra-red emissivity of almost 0.16, demonstrating its capability as selective coating for applications with operating temperatures up to 400°C, above which the nano-structure starts to deform. PMID:25418040

Improving NORTHCOM’s DSCA Capabilities

DTIC Science & Technology

2014-05-15

Response (Brief).” February 09, 2012 21 Kelly Vlahos , “Public Safety Today: CBRN Protection—From CCMRF to DCRF: Changing Letters for Better Results.” July...wildfire-response.aspx Kelly Vlahos , “Public Safety Today: CBRN Protection—From CCMRF to DCRF: Changing Letters for Better Results.” July 03, 2012

Analysis of laterally loaded long or intermediate drilled shafts of small or large diameter in layered soil.

DOT National Transportation Integrated Search

2008-12-01

This study has extended the capability of the SW model in order to predict the response of laterally loaded large diameter shafts considering 1) the influence of shaft type on the lateral shaft response; 2) the nonlinear behavior of shaft material an...

Teaching and Assessing Ethics and Social Responsibility in Undergraduate Science: A Position Paper

ERIC Educational Resources Information Center

Schultz, Madeleine

2014-01-01

Institutional graduate capabilities and discipline threshold learning outcomes require science students to demonstrate ethical conduct and social responsibility. However, the teaching and assessment of these concepts are not straightforward. Australian chemistry academics participated in a workshop in 2013 to discuss and develop teaching and…

Creating a Campus Based Community Emergency Response Team (CERT)

ERIC Educational Resources Information Center

Connolly, Maureen

2012-01-01

This article provides the reader with information regarding forming a community emergency response team (CERT) at a community college. College public safety departments are efficient entities in ordinary times. However, recent events at community colleges across the country have shown that there have been situations where their capabilities have…

44 CFR 334.2 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Policy. 334.2 Section 334.2... PREPAREDNESS GRADUATED MOBILIZATION RESPONSE § 334.2 Policy. (a) As established in Executive Order 12656, the policy of the United States is to have sufficient emergency response capabilities at all levels of...

78 FR 68774 - Onsite Emergency Response Capabilities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

[email protected] . SUPPLEMENTARY INFORMATION: I. Background As a result of the events at the Fukushima Dai-ichi... Force Review of Insights from the Fukushima Dai-ichi Accident'' (ADAMS Accession No. ML111861807), the... in Response to Fukushima Lessons Learned'' (ADAMS Accession No. ML11269A204). The NRC staff...

Computerized Adaptive Testing: Some Issues in Development.

ERIC Educational Resources Information Center

Orcutt, Venetia L.

The emergence of enhanced capabilities in computer technology coupled with the growing body of knowledge regarding item response theory has resulted in the expansion of computerized adaptive test (CAT) utilization in a variety of venues. Newcomers to the field need a more thorough understanding of item response theory (IRT) principles, their…

Development of an improved capability for predicting the response of highway bridges : final report.

DOT National Transportation Integrated Search

1986-01-01

This study compared experimental and analytical stress and deflection response of a simply-supported highway bridge as measured from a field test and as predicted from a finite-element analysis. The field test was conducted on one span of a six-span ...

The Load Capability of Piezoelectric Single Crystal Actuators

NASA Technical Reports Server (NTRS)

Xu, Tian-Bing; Su, Ji; Jiang, Xiaoning; Rehrig, Paul W.; Hackenberger, Wesley S.

2006-01-01

Piezoelectric lead magnesium niobate-lead titanate (PMN-PT) single crystal is one of the most promising materials for electromechanical device applications due to its high electrical field induced strain and high electromechanical coupling factor. PMN-PT single crystal-based multilayer stack actuators and multilayer stack-based flextensional actuators have exhibited high stroke and high displacement-voltage ratios. The actuation capabilities of these two actuators were evaluated using a newly developed method based upon a laser vibrometer system under various loading conditions. The measured displacements as a function of mechanical loads at different driving voltages indicate that the displacement response of the actuators is approximately constant under broad ranges of mechanical load. The load capabilities of these PMN-PT single crystal-based actuators and the advantages of the capability for applications will be discussed.

The Load Capability of Piezoelectric Single Crystal Actuators

NASA Technical Reports Server (NTRS)

Xu, Tian-Bing; Su, Ji; Jiang, Xiaoning; Rehrig, Paul W.; Hackenberger, Wesley S.

2007-01-01

Piezoelectric lead magnesium niobate-lead titanate (PMN-PT) single crystal is one of the most promising materials for electromechanical device applications due to its high electrical field induced strain and high electromechanical coupling factor. PMN-PT single crystal-based multilayer stack actuators and multilayer stack-based flextensional actuators have exhibited high stroke and high displacement-voltage ratios. The actuation capabilities of these two actuators were evaluated using a newly developed method based upon a laser vibrometer system under various loading conditions. The measured displacements as a function of mechanical loads at different driving voltages indicate that the displacement response of the actuators is approximately constant under broad ranges of mechanical load. The load capabilities of these PMN-PT single crystal-based actuators and the advantages of the capability for applications will be discussed.

Assessing the Organization and Capabilities of 4th Marine Logistics Group

DTIC Science & Technology

2010-05-14

Logistics Group (MLG) should adopt further organizational changes within specific parameters to complement the structure and capabilities of the Active...In order to enhance operational effectiveness and continue its mandated responsibility to augment and reinforce, 4th MLG should adopt further...of the Deputy Commandant, Installations and Logistics (DC, I&L), Marine Forces Reserve ( MFR ), and the MLGs. The paper also relies heavily on the

Material Stream Strategy for Lithium and Inorganics (U)

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

Safarik, Douglas Joseph; Dunn, Paul Stanton; Korzekwa, Deniece Rochelle

Design Agency Responsibilities: Manufacturing Support to meet Stockpile Stewardship goals for maintaining the nuclear stockpile through experimental and predictive modeling capability. Development and maintenance of Manufacturing Science expertise to assess material specifications and performance boundaries, and their relationship to processing parameters. Production Engineering Evaluations with competence in design requirements, material specifications, and manufacturing controls. Maintenance and enhancement of Aging Science expertise to support Stockpile Stewardship predictive science capability.

Small Countries’ Special Operations Forces Contribution to the NATO Response Force

DTIC Science & Technology

2014-06-13

tasks: Military Assistance, Direct Actions and Special Reconnaissance. The Jackal Stone exercise serves as a bedrock designed to build special...operations capabilities and improve interoperability among European partner nations. In Jackal Stone 2012, Army Major General Michael S. Repass, Commander...coalition or NATO operation, and the significance of teaming up with another 48 capable partner.96 Exercise Jackal Stone is an annual event and it is

Multi-Objective Optimization of System Capability Satisficing in Defense Acquisition

DTIC Science & Technology

2012-01-01

of System Capability Satisficing in Defense Acquisition 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Stevens Institute of Technology,School of Systems...Report (SAR) 18. NUMBER OF PAGES 27 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT

76 FR 39884 - Aviation Security Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

..., other non-governmental organizations (NGOs) and stakeholder representatives concerning potential risks to aviation infrastructure, passengers and cargo; response capabilities that NGOs and other...

Overview: Development of the National Ignition Facility and the Transition to a User Facility for the Ignition Campaign and High Energy Density Scientific Research

DOE PAGES

Moses, E. I.; Lindl, J. D.; Spaeth, M. L.; ...

2017-03-23

The National Ignition Facility (NIF) at Lawrence Livermore National Laboratory has been operational since March 2009 and has been transitioning to a user facility supporting ignition science, high energy density stockpile science, national security applications, and fundamental science. The facility has achieved its design goal of 1.8 MJ and 500 TW of 3ω light on target, and has performed target experiments with 1.9 MJ at peak powers of 410 TW. The National Ignition Campaign (NIC), established by the U.S. National Nuclear Security Administration in 2005, was responsible for transitioning NIF from a construction project to a national user facility. Besidesmore » the operation and optimization of the use of the NIF laser, the NIC program was responsible for developing capabilities including target fabrication facilities; cryogenic layering capabilities; over 60 optical, X-ray, and nuclear diagnostic systems; experimental platforms; and a wide range of other NIF facility infrastructure. This study provides a summary of some of the key experimental results for NIF to date, an overview of the NIF facility capabilities, and the challenges that were met in achieving these capabilities. Finally, they are covered in more detail in the papers that follow.« less

Overview: Development of the National Ignition Facility and the Transition to a User Facility for the Ignition Campaign and High Energy Density Scientific Research

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

Moses, E. I.; Lindl, J. D.; Spaeth, M. L.

The National Ignition Facility (NIF) at Lawrence Livermore National Laboratory has been operational since March 2009 and has been transitioning to a user facility supporting ignition science, high energy density stockpile science, national security applications, and fundamental science. The facility has achieved its design goal of 1.8 MJ and 500 TW of 3ω light on target, and has performed target experiments with 1.9 MJ at peak powers of 410 TW. The National Ignition Campaign (NIC), established by the U.S. National Nuclear Security Administration in 2005, was responsible for transitioning NIF from a construction project to a national user facility. Besidesmore » the operation and optimization of the use of the NIF laser, the NIC program was responsible for developing capabilities including target fabrication facilities; cryogenic layering capabilities; over 60 optical, X-ray, and nuclear diagnostic systems; experimental platforms; and a wide range of other NIF facility infrastructure. This study provides a summary of some of the key experimental results for NIF to date, an overview of the NIF facility capabilities, and the challenges that were met in achieving these capabilities. Finally, they are covered in more detail in the papers that follow.« less

Determine the Dynamic Response to Androgen-Blockade Therapy in Circulating Tumor Cells of CRPC Patients by Transcription-Based Reporter Vectors

DTIC Science & Technology

2016-08-01

green fluorescent reporter gene. Specific Aim 2: To evaluate the functional capability of Ad-mediated CTC detection and the response to AR...6 Specific Aim 3: To evaluate the therapeutic responses to AR antagonists in CTCs of CRPC patients before, during and after AR blockade...A., Mali, A., Khirade, M. & Bapat, S. A tumor deconstruction platform identifies definitive end points in the evaluation of drug responses. Oncogene

Heterogeneity in acute undifferentiated leukemia.

PubMed

LeMaistre, A; Childs, C C; Hirsch-Ginsberg, C; Reuben, J; Cork, A; Trujillo, J M; Andersson, B; McCredie, K B; Freireich, E; Stass, S A

1988-01-01

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.

The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison.

PubMed

Burnett, A K; Hills, R K; Hunter, A E; Milligan, D; Kell, W J; Wheatley, K; Yin, J; McMullin, M F; Dignum, H; Bowen, D; Russell, N H

2013-01-01

The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32-0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.

Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory.

PubMed

Hung, Hui-Chi; Hsiao, Ya-Hsin; Gean, Po-Wu

2015-10-01

It is now recognized that neurogenesis occurs throughout life predominantly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. In the present study, we investigated the relationship between neurogenesis in the amygdala and extinction of fear memory. Mice received 15 tone-footshock pairings. Twenty-four hours after training, the mice were given 15 tone-alone trials (extinction training) once per day for 7 days. Two hours before extinction training, the mice were injected intraperitoneally with 5-bromo-3-deoxyuridine (BrdU). BrdU-positive and NeuN-positive cells were analyzed 52 days after the training. A group of mice that received tone-footshock pairings but no extinction training served as controls (FC+No-Ext). The number of BrdU(+)/NeuN(+) cells was significantly higher in the extinction (FC+Ext) than in the FC+No-Ext mice. Proliferation inhibitor methylazoxymethanol acetate (MAM) or DNA synthesis inhibitor cytosine arabinoside (Ara-C) reduced neurogenesis and retarded extinction. Silencing Sonic hedgehog (Shh) gene with short hairpin interfering RNA (shRNA) by means of a retrovirus expression system to knockdown Shh specifically in the mitotic neurons reduced neurogenesis and retarded extinction. By contrast, over-expression of Shh increased neurogenesis and facilitated extinction. These results suggest that amygdala neurogenesis and Shh signaling are involved in the extinction of fear memory. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The change of nuclear LC3 distribution in acute myeloid leukemia cells.

PubMed

Guo, Wenjian; Jin, Jingrui; Pan, Jiajia; Yao, Rongxing; Li, Xia; Huang, Xin; Ma, Zhixing; Huang, Sujuan; Yan, Xiao; Jin, Jie; Dong, Aishu

2018-05-09

Making sure the change of nuclear LC3 distribution in the autophagy of acute myeloid leukemia (AML) cell and finding out the regulation mechanism may lead to a breakthrough for killing AML cells. Western blots were performed to assess the expression of autophagy proteins. Changes in the LC3 distribution were monitored by immunofluorescence assays together with western blots, and the expression levels of Sirt1, DOR, Beclin1, HMGB1, and AMPK mRNA were detected via fluorescent quantitative PCR. The effects of Sirt1 and DOR on cell proliferation and survival were analyzed by MTT, flow cytometry, and western blotting assays. We found that treating AML cells with Ara-c or Sorafenib resulted in autophagy enhancement, and when autophagy was enhanced, nuclear LC3 moved into the cytoplasm. Notably, when autophagy was inhibited by blocking the nuclear LC3 shift, the cytotoxicity of drugs was enhanced. Our results also identified Sirt1 and DOR as regulatory molecules for the observed nuclear LC3 shift, and these molecules further affected the expression of Beclin1, HMGB1, and AMPK. Our results suggest the distribution of nuclear LC3 can be a novel way for further studying death of AML cells,and the regulatory molecules may be new targets for treating AML. Copyright © 2018 Elsevier Inc. All rights reserved.

Systems metabolic engineering of Escherichia coli for production of the antitumor drugs violacein and deoxyviolacein.

PubMed

Rodrigues, André L; Trachtmann, Nathalie; Becker, Judith; Lohanatha, Ananta F; Blotenberg, Jana; Bolten, Christoph J; Korneli, Claudia; de Souza Lima, André O; Porto, Luismar M; Sprenger, Georg A; Wittmann, Christoph

2013-11-01

Violacein and deoxyviolacein are interesting therapeutics against pathogenic bacteria and viruses as well as tumor cells. In the present work, systems-wide metabolic engineering was applied to target Escherichia coli, a widely accepted recombinant host in pharmaceutical biotechnology, for production of these high-value products. The basic producer, E. coli dVio-1, that expressed the vioABCE cluster from Chromobacterium violaceum under control of the inducible araC system, accumulated 180 mg L(-1) of deoxyviolacein. Targeted intracellular metabolite analysis then identified bottlenecks in tryptophan supporting pathways, the major product building block. This was used for comprehensive engineering of serine, chorismate and tryptophan biosynthesis and the non-oxidative pentose-phosphate pathway. The final strain, E. coli dVio-6, accumulated 320 mg L(-1) deoxyviolacein in shake flask cultures. The created chassis of a high-flux tryptophan pathway was complemented by genomic integration of the vioD gene of Janthinobacterium lividum, which enabled exclusive production of violacein. In a fed-batch process, the resulting producer E. coli Vio-4 accumulated 710 mg L(-1) of the desired product. With straightforward broth extraction and subsequent crystallization, violacein could be obtained with 99.8% purity. This demonstrates the potential of E. coli as a platform for production of tryptophan based therapeutics. Copyright © 2013 Elsevier Inc. All rights reserved.

Divergent homologs of the predicted small RNA BpCand697 in Burkholderia spp.

NASA Astrophysics Data System (ADS)

Damiri, Nadzirah; Mohd-Padil, Hirzahida; Firdaus-Raih, Mohd

2015-09-01

The small RNA (sRNA) gene candidate, BpCand697 was previously reported to be unique to Burkholderia spp. and is encoded at 3' non-coding region of a putative AraC family transcription regulator gene. This study demonstrates the conservation of BpCand697 sequence across 32 Burkholderia spp. including B. pseudomallei, B. mallei, B. thailandensis and Burkholderia sp. by integrating both sequence homology and secondary structural analyses of BpCand697 within the dataset. The divergent sequence of BpCand697 was also used as a discriminatory power in clustering the dataset according to the potential virulence of Burkholderia spp., showing that B. thailandensis was clearly secluded from the virulent cluster of B. pseudomallei and B. mallei. Finally, the differential co-transcript expression of BpCand697 and its flanking gene, bpsl2391 was detected in Burkholderia pseudomallei D286 after grown under two different culture conditions using nutrient-rich and minimal media. It is hypothesized that the differential expression of BpCand697-bpsl2391 co-transcript between the two standard prepared media might correlate with nutrient availability in the culture media, suggesting that the physical co-localization of BpCand697 in B. pseudomallei D286 might be directly or indirectly involved with the transcript regulation of bpsl2391 under the selected in vitro culture conditions.

Study on the Preparation and Antileukemic Activity of New Lipophilic 1-β-D-arabinofuranosylcytosine Derivatives

NASA Astrophysics Data System (ADS)

Chu, Yanyan; Tian, Zhenhua; Hou, Yingwei; Li, Wenbao

2018-04-01

Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), isolated from a Caribbean sponge species Tethyacrypta, is the first antitumor drug from a marine resource. In 1980, the US Food and Drug Administration approved this drug for the treatment of different types of leukemia. This drug has a short plasma half-life, low stability, limited bioavailability, and severe side effects. To improve stability and bioavailability, we synthesized nine novel derivatives by blocking the cytarabine metabolic sites and improving lipophilicity. The cLogP values of the newly synthesized compounds were calculated. All the synthesized compounds were more lipophilic than cytarabine, resulting in membrane permeability and bioavailability improvement. The antitumor activities against leukemia cell line HL-60 were evaluated by using the MTT assay. The bioassay results revealed that the IC50 values of compounds 5, 8 and 9 were 0.080, 0.090 and 0.057 μmol L-1, respectively, which was similar with that of cytarabine (0.056 μmol L-1). In comparison, compound 4 with a phosphate group at O5' was inactive. Because phosphoester bonds are easily hydrolyzed by alkaline phosphatase and are commonly used in producing prodrug strategies, compound 4 might also be metabolized in vivo and generate compound 3 or even cytarabine through a multi-step reaction. Thus, compound 4 might be a promising compound to be developed as a prodrug.

Coordinated and sequential transcription of the cyprinid herpesvirus-3 annotated genes.

PubMed

Ilouze, Maya; Dishon, Arnon; Kotler, Moshe

2012-10-01

Cyprinid herpesvirus-3 (CyHV-3) is the cause of a fatal disease in carp and koi fish. The disease is seasonal and appears when water temperatures range from 18 to 28°C. CyHV-3 is a member of the Alloherpesviridae, a family in the Herpesvirales order that encompasses mammalian, avian and reptilian viruses. CyHV-3 is a large double-stranded DNA (dsDNA) herpesvirus with a genome of approximately 295kbp, divergent from other mammalian, avian and reptilian herpesviruses, but bearing several genes similar to cyprinid herpesvirus-1 (CyHV-1), CyHV-2, anguillid herpesvirus-1 (AngHV-1), ictalurid herpesvirus-1 (IcHV-1) and ranid herpes virus-1 (RaHV-1). Here we show that viral DNA synthesis commences 4-8h post-infection (p.i.), and is completely inhibited by pre-treatment with cytosine β-d-arabinofuranoside (Ara-C). Transcription of CyHV-3 genes initiates after infection as early as 1-2h p.i., and precedes viral DNA synthesis. All 156 annotated open reading frames (ORFs) of the CyHV-3 genome are transcribed into RNAs, most of which can be classified into immediate early (IE or α), early (E or β) and late (L or γ) classes, similar to all other herpesviruses. Several ORFs belonging to these groups are clustered along the viral genome. Copyright © 2012 Elsevier B.V. All rights reserved.

Business Systems Branch Abilities, Capabilities, and Services Web Page

NASA Technical Reports Server (NTRS)

Cortes-Pena, Aida Yoguely

2009-01-01

During the INSPIRE summer internship I acted as the Business Systems Branch Capability Owner for the Kennedy Web-based Initiative for Communicating Capabilities System (KWICC), with the responsibility of creating a portal that describes the services provided by this Branch. This project will help others achieve a clear view ofthe services that the Business System Branch provides to NASA and the Kennedy Space Center. After collecting the data through the interviews with subject matter experts and the literature in Business World and other web sites I identified discrepancies, made the necessary corrections to the sites and placed the information from the report into the KWICC web page.

Statistical Capability Study of a Helical Grinding Machine Producing Screw Rotors

NASA Astrophysics Data System (ADS)

Holmes, C. S.; Headley, M.; Hart, P. W.

2017-08-01

Screw compressors depend for their efficiency and reliability on the accuracy of the rotors, and therefore on the machinery used in their production. The machinery has evolved over more than half a century in response to customer demands for production accuracy, efficiency, and flexibility, and is now at a high level on all three criteria. Production equipment and processes must be capable of maintaining accuracy over a production run, and this must be assessed statistically under strictly controlled conditions. This paper gives numerical data from such a study of an innovative machine tool and shows that it is possible to meet the demanding statistical capability requirements.

Estimation of Supersonic Stage Separation Aerodynamics of Winged-Body Launch Vehicles Using Response Surface Methods

NASA Technical Reports Server (NTRS)

Erickson, Gary E.

2010-01-01

Response surface methodology was used to estimate the longitudinal stage separation aerodynamic characteristics of a generic, bimese, winged multi-stage launch vehicle configuration at supersonic speeds in the NASA LaRC Unitary Plan Wind Tunnel. The Mach 3 staging was dominated by shock wave interactions between the orbiter and booster vehicles throughout the relative spatial locations of interest. The inference space was partitioned into several contiguous regions within which the separation aerodynamics were presumed to be well-behaved and estimable using central composite designs capable of fitting full second-order response functions. The underlying aerodynamic response surfaces of the booster vehicle in belly-to-belly proximity to the orbiter vehicle were estimated using piecewise-continuous lower-order polynomial functions. The quality of fit and prediction capabilities of the empirical models were assessed in detail, and the issue of subspace boundary discontinuities was addressed. Augmenting the central composite designs to full third-order using computer-generated D-optimality criteria was evaluated. The usefulness of central composite designs, the subspace sizing, and the practicality of fitting lower-order response functions over a partitioned inference space dominated by highly nonlinear and possibly discontinuous shock-induced aerodynamics are discussed.

Optimization of microwave-assisted extraction of total extract, stevioside and rebaudioside-A from Stevia rebaudiana (Bertoni) leaves, using response surface methodology (RSM) and artificial neural network (ANN) modelling.

PubMed

Ameer, Kashif; Bae, Seong-Woo; Jo, Yunhee; Lee, Hyun-Gyu; Ameer, Asif; Kwon, Joong-Ho

2017-08-15

Stevia rebaudiana (Bertoni) consists of stevioside and rebaudioside-A (Reb-A). We compared response surface methodology (RSM) and artificial neural network (ANN) modelling for their estimation and predictive capabilities in building effective models with maximum responses. A 5-level 3-factor central composite design was used to optimize microwave-assisted extraction (MAE) to obtain maximum yield of target responses as a function of extraction time (X 1 : 1-5min), ethanol concentration, (X 2 : 0-100%) and microwave power (X 3 : 40-200W). Maximum values of the three output parameters: 7.67% total extract yield, 19.58mg/g stevioside yield, and 15.3mg/g Reb-A yield, were obtained under optimum extraction conditions of 4min X 1 , 75% X 2 , and 160W X 3 . The ANN model demonstrated higher efficiency than did the RSM model. Hence, RSM can demonstrate interaction effects of inherent MAE parameters on target responses, whereas ANN can reliably model the MAE process with better predictive and estimation capabilities. Copyright © 2017. Published by Elsevier Ltd.

Spiritual and Affective Responses to a Physical Church and Corresponding Virtual Model.

PubMed

Murdoch, Matt; Davies, Jim

2017-11-01

Architectural and psychological theories posit that built environments have the potential to elicit complex psychological responses. However, few researchers have seriously explored this potential. Given the increasing importance and fidelity of virtual worlds, such research should explore whether virtual models of built environments are also capable of eliciting complex psychological responses. The goal of this study was to test these hypotheses, using a church, a corresponding virtual model, and an inclusive measure of state spirituality ("spiritual feelings"). Participants (n = 33) explored a physical church and corresponding virtual model, completing a measure of spiritual feelings after exploring the outside and inside of each version of the church. Using spiritual feelings after exploring the outside of the church as a baseline measure, change in state spirituality was assessed by taking the difference between spiritual feelings after exploring the inside and outside of the church (inside-outside) for both models. Although this change was greater in response to the physical church, there was no significant difference between the two models in eliciting such change in spiritual feelings. Despite the limitations of this exploratory study, these findings indicate that both built environments and corresponding virtual models are capable of evoking complex psychological responses.

RETRAN analysis of multiple steam generator blow down caused by an auxiliary feedwater steam-line break

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

Feltus, M.A.

1987-01-01

Analysis results for multiple steam generator blow down caused by an auxiliary feedwater steam-line break performed with the RETRAN-02 MOD 003 computer code are presented to demonstrate the capabilities of the RETRAN code to predict system transient response for verifying changes in operational procedures and supporting plant equipment modifications. A typical four-loop Westinghouse pressurized water reactor was modeled using best-estimate versus worst case licensing assumptions. This paper presents analyses performed to evaluate the necessity of implementing an auxiliary feedwater steam-line isolation modification. RETRAN transient analysis can be used to determine core cooling capability response, departure from nucleate boiling ratio (DNBR)more » status, and reactor trip signal actuation times.« less

Cell electrophysiology with carbon nanopipettes.

PubMed

Schrlau, Michael G; Dun, Nae J; Bau, Haim H

2009-03-24

The ability to monitor living cell behavior in real time and with high spatial resolution is vital for advancing our knowledge of cellular machinery and evaluating cellular response to various drugs. Here, we report the development and utilization of carbon-based nanoelectrodes for cell electrophysiology. We employ carbon nanopipettes (CNPs), novel carbon-based nanoprobes which integrate carbon nanopipes into the tips of pulled glass capillaries, to measure electrical signals in the mouse hippocampal cell line HT-22. Using a standard electrophysiology amplifier in current-clamp mode, we measured the resting membrane potential of cells and their transient membrane response to extracellular pharmacological agents. In addition to their superior injection capabilities reported previously, CNPs are capable of multifunctionality, enabling, for example, concurrent intracellular injection and electrical measurements without damaging cells.

Overview of practice management in child and adolescent psychiatry.

PubMed

Schreter, Robert K

2010-01-01

The manager of a psychiatric practice must create and direct a clinical delivery system, design and oversee the administrative services necessary to support the system, and guide the business operations that contribute to its success. Regardless of the size of the practice, the psychiatrist administrator must handle seven core administrative responsibilities and oversee individual functions and capabilities within each domain. These responsibilities include practice development, clinical services management, medical office operations, clinical management, information management, business management, and risk management. This article provides a roadmap for creating and sustaining successful clinical and administrative endeavors. It can also be used by existing practices as an audit instrument to provide a snapshot of current capabilities so that strengths as well as opportunities for continued growth can be identified.

Integrating international responses to complex emergencies, unconventional war, and terrorism.

PubMed

Burkle, Frederick M

2005-01-01

The world is experiencing unprecedented violence and threats of violence, taking the form of complex internal nation-state conflicts, unconventional or guerrilla warfare against established governments, and stateless threats of terrorism by potential biologic, chemical, and nuclear weapons. What happens locally has immediate ramifications internationally. Real and potential health consequences of these events have evoked global concerns and realization that capacities and capabilities to respond to such events require unparalleled integration, coordination, and cooperation of the international community. However, politics and the institutions singular governments form are inherently limited in their objectives and capability to effectively respond. Public health, broadly defined, must be recognized as a security and strategic requirement, one that serves to build a foundation for an international integrated response capacity.

Organizational Context and Capabilities for Integrating Care: A Framework for Improvement.

PubMed

Evans, Jenna M; Grudniewicz, Agnes; Baker, G Ross; Wodchis, Walter P

2016-08-31

Interventions aimed at integrating care have become widespread in healthcare; however, there is significant variability in their success. Differences in organizational contexts and associated capabilities may be responsible for some of this variability. This study develops and validates a conceptual framework of organizational capabilities for integrating care, identifies which of these capabilities may be most important, and explores the mechanisms by which they influence integrated care efforts. The Context and Capabilities for Integrating Care (CCIC) Framework was developed through a literature review, and revised and validated through interviews with leaders and care providers engaged in integrated care networks in Ontario, Canada. Interviews involved open-ended questions and graphic elicitation. Quantitative content analysis was used to summarize the data. The CCIC Framework consists of eighteen organizational factors in three categories: Basic Structures, People and Values, and Key Processes. The three most important capabilities shaping the capacity of organizations to implement integrated care interventions include Leadership Approach, Clinician Engagement and Leadership, and Readiness for Change. The majority of hypothesized relationships among organizational capabilities involved Readiness for Change and Partnering, emphasizing the complexity, interrelatedness and importance of these two factors to integrated care efforts. Organizational leaders can use the framework to determine readiness to integrate care, develop targeted change management strategies, and select appropriate partners with overlapping or complementary profiles on key capabilities. Researchers may use the results to test and refine the proposed framework, with a focus on the hypothesized relationships among organizational capabilities and between organizational capabilities and performance outcomes.

Physician capability to electronically exchange clinical information, 2011.

PubMed

Patel, Vaishali; Swain, Matthew J; King, Jennifer; Furukawa, Michael F

2013-10-01

To provide national estimates of physician capability to electronically share clinical information with other providers and to describe variation in exchange capability across states and electronic health record (EHR) vendors using the 2011 National Ambulatory Medical Care Survey Electronic Medical Record Supplement. Survey of a nationally representative sample of nonfederal office-based physicians who provide direct patient care. The survey was administered by mail with telephone follow-up and had a 61% weighted response rate. The overall sample consisted of 4326 respondents. We calculated estimates of electronic exchange capability at the national and state levels, and applied multivariate analyses to examine the association between the capability to exchange different types of clinical information and physician and practice characteristics. In 2011, 55% of physicians had computerized capability to send prescriptions electronically; 67% had the capability to view lab results electronically; 42% were able to incorporate lab results into their EHR; 35% were able to send lab orders electronically; and, 31% exchanged patient clinical summaries with other providers. The strongest predictor of exchange capability is adoption of an EHR. However, substantial variation exists across geography and EHR vendors in exchange capability, especially electronic exchange of clinical summaries. In 2011, a majority of office-based physicians could exchange lab and medication data, and approximately one-third could exchange clinical summaries with patients or other providers. EHRs serve as a key mechanism by which physicians can exchange clinical data, though physicians' capability to exchange varies by vendor and by state.

Response time for multilayered platinum resistance thermometers

NASA Technical Reports Server (NTRS)

Pandey, D. K.; Ash, R. L.

1985-01-01

Response time constants for several multilayered temperature transducers were determined numerically by using Martin Marietta's MITAS software package which is available at NASA Langley Research Center. Present results were found in close agreement with the solutions reported in the literature, thus, the capability of MITAS was justified. On the basis of experiences gained, the MITAS is recommended for use in predicting the response time constants of sensors by an in-situ technique.

Spacecraft Demand Tasking and Skip Entry Responsive Maneuvers

DTIC Science & Technology

2011-06-01

Introduction General Issue Growing in prominence within the policy decisions of the U.S. Department of Defense, the term “responsive space ” represents a...shift from a solution-oriented to a capabilities-oriented approach to space acquisition and space system design, in which the performance of a new...by the development of spacecraft and launch vehicles, an aspect of the responsive space initiative that has garnered increased attention within the

Seeing the Elephant -- Consequence Management Policy for the Department of Defense

DTIC Science & Technology

2001-05-01

required for effective Consequence Management. The three response tiers allows the DoD to provide a predesignated level of support to the appropriate Federal...recommendation is the creation of a tiered response capability that balances time and tasks required for effective Consequence Management. The three...the response required for toxic chemical events. The third tier is reserved for the actions required for the Consequence Management for a biological

75 FR 22599 - Draft Guidance for Industry and Food and Drug Administration Staff; Food and Drug Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... office in processing your request, or fax your request to CDRH to 301-847-8149. See the SUPPLEMENTARY... guidance you are requesting. A search capability for all CDRH guidance documents is available at http://www... Response Responses Response Total Hours CDRH 110 1 110 12 1,320 CBER 4 1 4 12 48 Total 1,368 \\1\\ There are...

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity.

PubMed

Yuba, Eiji; Sakaguchi, Naoki; Kanda, Yuhei; Miyazaki, Maiko; Koiwai, Kazunori

2017-11-04

(1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC) and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2) Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3) Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA) into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4) Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

Ultrasonic Resonance Spectroscopy of Composite Rims for Flywheel Rotors

NASA Technical Reports Server (NTRS)

Harmon, Laura M.; Baaklini, George Y.

2002-01-01

Flywheel energy storage devices comprising multilayered composite rotor systems are being studied extensively for utilization in the International Space Station. These composite material systems were investigated with a recently developed ultrasonic resonance spectroscopy technique. The ultrasonic system employs a continuous swept-sine waveform and performs a fast Fourier transform (FFT) on the frequency response spectrum. In addition, the system is capable of equalizing the amount of energy at each frequency. Equalization of the frequency spectrum, along with interpretation of the second FFT, aids in the evaluation of the fundamental frequency. The frequency responses from multilayered material samples, with and without known defects, were analyzed to assess the capabilities and limitations of this nondestructive evaluation technique for material characterization and defect detection. Amplitude and frequency changes were studied from ultrasonic responses of thick composite rings and a multiring composite rim. A composite ring varying in thickness was evaluated to investigate the full thickness resonance. The frequency response characteristics from naturally occurring voids in a composite ring were investigated. Ultrasonic responses were compared from regions with and without machined voids in a composite ring and a multiring composite rim. Finally, ultrasonic responses from the multiring composite rim were compared before and after proof spin testing to 63,000 rpm.

Nontraditional Teaching Techniques and Critical Thinking in an Introductory Postsecondary Environmental Science Course

ERIC Educational Resources Information Center

Buerdsell, Sherri Lynn

2009-01-01

As an institution of higher education and as a Hispanic-serving institution, New Mexico State University has a responsibility to its students to provide the skills and experiences necessary for each and every student to become a responsible, reflective citizen, capable of making informed decisions. Postsecondary science has traditionally been…

The Redirection: An Indicator of How Teachers Respond to Student Thinking

ERIC Educational Resources Information Center

Lineback, Jennifer Evarts

2015-01-01

Responsive teaching occurs when teachers take up and "respond" to their students' ideas during instruction (J. L. Pierson, 2008). Although responsive teaching is gaining recognition as an effective strategy for encouraging student learning, few methods of analysis are capable of characterizing the different ways in which teachers take up…

More About Hazard-Response Robot For Combustible Atmospheres

NASA Technical Reports Server (NTRS)

Stone, Henry W.; Ohm, Timothy R.

1995-01-01

Report presents additional information about design and capabilities of mobile hazard-response robot called "Hazbot III." Designed to operate safely in combustible and/or toxic atmosphere. Includes cameras and chemical sensors helping human technicians determine location and nature of hazard so human emergency team can decide how to eliminate hazard without approaching themselves.

Psychological Factors Capable of Preventing the Inhibition of Antibody Responses in Separated Infant Monkeys.

ERIC Educational Resources Information Center

Coe, Christopher L.; And Others

1987-01-01

Capacity of infant monkeys to mount an antibody response to viral challenge was evaluated after monkeys' removal from their mothers in several social and physical environments. Results indicated that trauma of separation was reduced when infants were familiar with the separation environment or familiar social companions were available. (PCB)

30 CFR 254.45 - Verifying the capabilities of your response equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES LOCATED SEAWARD OF THE... Protocol for the Evaluation of Oil-Spill Containment Booms,” available from BSEE, for guidance. Performance... document “Suggested Test Protocol for the Evaluation of Oil Spill Skimmers for the OCS,” available from...

30 CFR 254.45 - Verifying the capabilities of your response equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS FOR FACILITIES LOCATED SEAWARD OF THE... Protocol for the Evaluation of Oil-Spill Containment Booms,” available from BSEE, for guidance. Performance... document “Suggested Test Protocol for the Evaluation of Oil Spill Skimmers for the OCS,” available from...

Business Models for Cost Sharing & Capability Sustainment

DTIC Science & Technology

2012-08-18

digital technology into existing mechanical products and their supporting processes can only work correctly if the firm carrying it out changes its entire...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed...Capability Sustainment 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK

Information Fusion and Extraction Priorities for Australia’s Information Capability

DTIC Science & Technology

2004-03-01

also been in response to the global threats of terrorism and the utilisation of weapons of mass destruction or long-range ballistic missiles by...missiles and weapons of mass destruction by rogue states [4]. Accordingly, “maintaining first-rate intelligence capabilities, developing a comprehensive...number of customised views. For example, temporal data based on a particular activity may be displayed in a variety of modes on a grid or clock face

Canadian Forces in Joint Fires Support - Human Factors Analysis: Coalition Operations

DTIC Science & Technology

2010-08-01

mesure/l’estimation des dommages collatéraux (EDC). Outil pour comprendre l’EDC de certains pays comparativement à celle des membres de l’OTAN et...Program (TDP). The TDP is aimed at concept development, evaluation for force design , and the demonstration of technologies fostered by Defence Research...logistics and the designation of targets on the joint targeting list. • Tactical capability / response time / training. The tactical capability of a fire

Seeing Eye Drones: How The DOD Can Transform CBM And Disaster Response In The Homeland

DTIC Science & Technology

2016-12-01

thesis explores the possibility of integrating small unmanned aircraft systems (sUAS) with video capability and CBRN detection and identification sensors...small, unmanned aircraft systems (sUAS) with video capability and CBRN detection and identification sensors for use by National Guard civil support...CBRN) and hazardous material (HAZMAT) materials, as well as providing video to the incident commander. One of the primary benefits of providing

Mutants of Pseudomonas cepacia G4 defective in catabolism of aromatic compounds and trichloroethylene.

PubMed Central

Shields, M S; Montgomery, S O; Cuskey, S M; Chapman, P J; Pritchard, P H

1991-01-01

Pseudomonas cepacia G4 possesses a novel pathway of toluene catabolism that is shown to be responsible for the degradation of trichloroethylene (TCE). This pathway involves conversion of toluene via o-cresol to 3-methylcatechol. In order to determine the enzyme of toluene degradation that is responsible for TCE degradation, chemically induced mutants, blocked in the toluene ortho-monooxygenase (TOM) pathway of G4, were examined. Mutants of the phenotypic class designated TOM A- were all defective in their ability to oxidize toluene, o-cresol, m-cresol, and phenol, suggesting that a single enzyme is responsible for conversion of these compounds to their hydroxylated products (3-methylcatechol from toluene, o-cresol, and m-cresol and catechol from phenol) in the wild type. Mutants of this class did not degrade TCE. Two other mutant classes which were blocked in toluene catabolism, TOM B-, which lacked catechol-2,3-dioxygenase, and TOM C-, which lacked 2-hydroxy-6-oxoheptadienoic acid hydrolase activity, were fully capable of TCE degradation. Therefore, TCE degradation is directly associated with the monooxygenation capability responsible for toluene, cresol, and phenol hydroxylation. PMID:1892384

Seismic Analysis Capability in NASTRAN

NASA Technical Reports Server (NTRS)

Butler, T. G.; Strang, R. F.

1984-01-01

Seismic analysis is a technique which pertains to loading described in terms of boundary accelerations. Earthquake shocks to buildings is the type of excitation which usually comes to mind when one hears the word seismic, but this technique also applied to a broad class of acceleration excitations which are applied at the base of a structure such as vibration shaker testing or shocks to machinery foundations. Four different solution paths are available in NASTRAN for seismic analysis. They are: Direct Seismic Frequency Response, Direct Seismic Transient Response, Modal Seismic Frequency Response, and Modal Seismic Transient Response. This capability, at present, is invoked not as separate rigid formats, but as pre-packaged ALTER packets to existing RIGID Formats 8, 9, 11, and 12. These ALTER packets are included with the delivery of the NASTRAN program and are stored on the computer as a library of callable utilities. The user calls one of these utilities and merges it into the Executive Control Section of the data deck to perform any of the four options are invoked by setting parameter values in the bulk data.

The Transfer Function Model as a Tool to Study and Describe Space Weather Phenomena

NASA Technical Reports Server (NTRS)

Porter, Hayden S.; Mayr, Hans G.; Bhartia, P. K. (Technical Monitor)

2001-01-01

The Transfer Function Model (TFM) is a semi-analytical, linear model that is designed especially to describe thermospheric perturbations associated with magnetic storms and substorm. activity. It is a multi-constituent model (N2, O, He H, Ar) that accounts for wind induced diffusion, which significantly affects not only the composition and mass density but also the temperature and wind fields. Because the TFM adopts a semianalytic approach in which the geometry and temporal dependencies of the driving sources are removed through the use of height-integrated Green's functions, it provides physical insight into the essential properties of processes being considered, which are uncluttered by the accidental complexities that arise from particular source geometrie and time dependences. Extending from the ground to 700 km, the TFM eliminates spurious effects due to arbitrarily chosen boundary conditions. A database of transfer functions, computed only once, can be used to synthesize a wide range of spatial and temporal sources dependencies. The response synthesis can be performed quickly in real-time using only limited computing capabilities. These features make the TFM unique among global dynamical models. Given these desirable properties, a version of the TFM has been developed for personal computers (PC) using advanced platform-independent 3D visualization capabilities. We demonstrate the model capabilities with simulations for different auroral sources, including the response of ducted gravity waves modes that propagate around the globe. The thermospheric response is found to depend strongly on the spatial and temporal frequency spectra of the storm. Such varied behavior is difficult to describe in statistical empirical models. To improve the capability of space weather prediction, the TFM thus could be grafted naturally onto existing statistical models using data assimilation.

Rapid SAR and GPS Measurements and Models for Hazard Science and Situational Awareness

NASA Astrophysics Data System (ADS)

Owen, S. E.; Yun, S. H.; Hua, H.; Agram, P. S.; Liu, Z.; Moore, A. W.; Rosen, P. A.; Simons, M.; Webb, F.; Linick, J.; Fielding, E. J.; Lundgren, P.; Sacco, G. F.; Polet, J.; Manipon, G.

2016-12-01

The Advanced Rapid Imaging and Analysis (ARIA) project for Natural Hazards is focused on rapidly generating higher level geodetic imaging products and placing them in the hands of the solid earth science and local, national, and international natural hazard communities by providing science product generation, exploration, and delivery capabilities at an operational level. Space-based geodetic measurement techniques such as Interferometric Synthetic Aperture Radar (InSAR), Differential Global Positioning System (DGPS), SAR-based change detection, and image pixel tracking have recently become critical additions to our toolset for understanding and mapping the damage caused by earthquakes, volcanic eruptions, landslides, and floods. Analyses of these data sets are still largely handcrafted following each event and are not generated rapidly and reliably enough for response to natural disasters or for timely analysis of large data sets. The ARIA project, a joint venture co-sponsored by California Institute of Technology (Caltech) and by NASA through the Jet Propulsion Laboratory (JPL), has been capturing the knowledge applied to these responses and building it into an automated infrastructure to generate imaging products in near real-time that can improve situational awareness for disaster response. In addition, the ARIA project is developing the capabilities to provide automated imaging and analysis capabilities necessary to keep up with the imminent increase in raw data from geodetic imaging missions planned for launch by NASA, as well as international space agencies. We will present the progress we have made on automating the analysis of SAR data for hazard monitoring and response using data from Sentinel 1a/b as well as continuous GPS stations. Since the beginning of our project, our team has imaged events and generated response products for events around the world. These response products have enabled many conversations with those in the disaster response community about the potential usefulness of rapid SAR and GPS-based information. We will present progress on our data system technology that enables rapid and reliable production of imagery, as well as lessons learned from our engagement with FEMA and others in the hazard response community on the important actionable information that they need.

Project Responder: technology needs for local emergency response

NASA Astrophysics Data System (ADS)

Beakley, Guy; Garwin, Thomas; Pollard, Neal A.; Singley, George T., III; Tuohy, Robert V.; Lupo, Jasper

2003-09-01

Since April 2001, the Oklahoma City National Memorial Institute for the Prevention of Terrorism has funded an effort by Hicks &Associates, Inc. and the Terrorism Research Center, Inc., aimed ultimately at improving local, state, and federal emergency responders" capabilities for mitigating the effects of chemical, biological, radiological, nuclear or explosive/ incendiary (CBRNE) terrorism. This effort, titled "Project Responder," began by developing an understanding of how state and local responders view their current capabilities, shortfalls, and needs. This paper discusses some of the results of this first phase of the effort that has resulted in a comprehensive report titled "Emergency Responders" Needs, Goals, and Priorities." This paper addresses two of the capabilities from that report which we believe are of most interest to this conference. There are ten other capabilities discussed in the report, which may also be of interest.

Coupled Thermo-Electro-Magneto-Elastic Response of Smart Stiffened Panels

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Yarrington, Phillip W.

2009-01-01

This report documents the procedures developed for incorporating smart laminate and panel analysis capabilities within the HyperSizer aerospace structural sizing software package. HyperSizer analyzes stiffened panels composed of arbitrary composite laminates through stiffener homogenization, or "smearing " techniques. The result is an effective constitutive equation for the stiffened panel that is suitable for use in a full vehicle-scale finite element analysis via MSC/NASTRAN. The existing thermo-elastic capabilities of HyperSizer have herein been extended to include coupled thermo-electro-magneto-elastic analysis capabilities. This represents a significant step toward realization of design tools capable of guiding the development of the next generation of smart aerospace structures. Verification results are presented that compare the developed smart HyperSizer capability with an ABAQUS piezoelectric finite element solution for a facesheet-flange combination. These results show good agreement between HyperSizer and ABAQUS, but highlight a limitation of the HyperSizer formulation in that constant electric field components are assumed.

Facilities to Support Beamed Energy Launch Testing at the Laser Hardened Materials Evaluation Laboratory (LHMEL)

NASA Astrophysics Data System (ADS)

Lander, Michael L.

2003-05-01

The Laser Hardened Materials Evaluation Laboratory (LHMEL) has been characterizing material responses to laser energy in support of national defense programs and the aerospace industry for the past 26 years. This paper reviews the overall resources available at LHMEL to support fundamental materials testing relating to impulse coupling measurement and to explore beamed energy launch concepts. Located at Wright-Patterson Air Force Base, Ohio, LHMEL is managed by the Air Force Research Laboratory Materials Directorate AFRL/MLPJ and operated by Anteon Corporation. The facility's advanced hardware is centered around carbon dioxide lasers producing output power up to 135kW and neodymium glass lasers producing up to 10 kilojoules of repetitively pulsed output. The specific capabilities of each laser device and related optical systems are discussed. Materials testing capabilities coupled with the laser systems are also described including laser output and test specimen response diagnostics. Environmental simulation capabilities including wind tunnels and large-volume vacuum chambers relevant to beamed energy propulsion are also discussed. This paper concludes with a summary of the procedures and methods by which the facility can be accessed.

Learning from LANCE: Developing a Web Portal Infrastructure for NASA Earth Science Data (Invited)

NASA Astrophysics Data System (ADS)

Murphy, K. J.

2013-12-01

NASA developed the Land Atmosphere Near real-time Capability for EOS (LANCE) in response to a growing need for timely satellite observations by applications users, operational agencies and researchers. EOS capabilities originally intended for long-term Earth science research were modified to deliver satellite data products with sufficient latencies to meet the needs of the NRT user communities. LANCE products are primarily distributed as HDF data files for analysis, however novel capabilities for distribution of NRT imagery for visualization have been added which have expanded the user base. Additionally systems to convert data to information such as the MODIS hotspot/active fire data are also provided through the Fire Information for Resource Management System (FIRMS). LANCE services include: FTP/HTTP file distribution, Rapid Response (RR), Worldview, Global Imagery Browse Services (GIBS) and FIRMS. This paper discusses how NASA has developed services specifically for LANCE and is taking the lessons learned through these activities to develop an Earthdata Web Infrastructure. This infrastructure is being used as a platform to support development of data portals that address specific science issues for much of EOSDIS data.

Development of display design and command usage guidelines for Spacelab experiment computer applications

NASA Technical Reports Server (NTRS)

Dodson, D. W.; Shields, N. L., Jr.

1979-01-01

Individual Spacelab experiments are responsible for developing their CRT display formats and interactive command scenarios for payload crew monitoring and control of experiment operations via the Spacelab Data Display System (DDS). In order to enhance crew training and flight operations, it was important to establish some standardization of the crew/experiment interface among different experiments by providing standard methods and techniques for data presentation and experiment commanding via the DDS. In order to establish optimum usage guidelines for the Spacelab DDS, the capabilities and limitations of the hardware and Experiment Computer Operating System design had to be considered. Since the operating system software and hardware design had already been established, the Display and Command Usage Guidelines were constrained to the capabilities of the existing system design. Empirical evaluations were conducted on a DDS simulator to determine optimum operator/system interface utilization of the system capabilities. Display parameters such as information location, display density, data organization, status presentation and dynamic update effects were evaluated in terms of response times and error rates.

Crisis management, capabilities and preparedness: the case of public hospitals in Iran.

PubMed

Najafbagy, Reza

2010-01-01

Crises occurred in recent decades show that organizations' preparedness to predict and respond to undesired problems is directly related to the degree of their capabilities and preparedness to manage crises in this context, hospitals compared to other organizations are more viable to suffer damages if a crisis occurs. This study investigates the degree of public hospitals capabilities and preparedness to handled possible crises. Responses from hospital managers and directors show that most of them were not familiar with crisis management, while majority of them mentioned that they had crisis management plan and committee in their hospitals. Moreover, most of the respondents believed that if a crisis occurs in the hospital, patients, personnel and documents will be the first victims of the crisis. The study also indicates that having a crisis plan and crisis committee without being familiar with knowledge of crisis management, do not help managers to cope with crisis. Moreover, correlations show that older managers were more familiar with crisis management experiences abroad, and defined responsibilities contributed to setting up crisis committee, and taking crisis seriously.

ERLN Water Focus Area

EPA Pesticide Factsheets

The Water Laboratory Alliance (WLA), within Environmental Response Laboratory Network, maintains analytical capability and capacity in the event of intentional and unintentional water contamination with chemical, biological and radiochemical contaminants.

Weapons of Mass Destruction Technology Evaluation and Training Range

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

Kevin Larry Young

2009-05-01

The Idaho National Laboratory (INL) has a long history for providing technology evaluation and training for military and other federal level Weapons of Mass Destruction (WMD) response agencies. Currently there are many federal organizations and commercial companies developing technologies related to detecting, assessing, mitigating and protecting against hazards associated with a WMD event. Unfortunately, very few locations exist within the United States where WMD response technologies are realistically field tested and evaluated using real chemical, biological, radiological, nuclear and explosive materials. This is particularly true with biological and radiological hazards. Related to this lack of adequate WMD, multi-hazard technology testingmore » capability is the shortage of locations where WMD response teams can train using actual chemical, biological, and radiological material or highly realistic simulates. In response to these technology evaluation and training needs, the INL has assembled a consortium of subject matter experts from existing programs and identified dedicated resources for the purpose of establishing an all-hazards, WMD technology evaluation and training range. The author describes the challenges associated with creating the all-hazards WMD technology evaluation and training range and lists the technical, logistical and financial benefits of an all-hazards technology evaluation and training range. Current resources and capabilities for conducting all-hazard technology evaluation and training at the INL are identified. Existing technology evaluation and training programs at the INL related to radiological, biological and chemical hazards are highlighted, including successes and lessons learned. Finally, remaining gaps in WMD technology evaluation and training capabilities are identified along with recommendations for closing those gaps.« less

Making vaccines "on demand": a potential solution for emerging pathogens and biodefense?

PubMed

De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

2013-09-01

The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of "novel pathogens" such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process-from genome to gene sequence, ready to insert in a DNA plasmid-can now be accomplished in less than 24 h. While these vaccines are by no means "standard," the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.

Data and Geocomputation: Time Critical Mission Support for the 2017 Hurricane Season

NASA Astrophysics Data System (ADS)

Bhaduri, B. L.; Tuttle, M.; Rose, A.; Sanyal, J.; Thakur, G.; White, D.; Yang, H. H.; Laverdiere, M.; Whitehead, M.; Taylor, H.; Jacob, M.

2017-12-01

A strong spatial data infrastructure and geospatial analysis capabilities are nucleus to the decision-making process during emergency preparedness, response, and recovery operations. For over a decade, the U.S. Department of Energy's Oak Ridge National Laboratory has been developing critical data and analytical capabilities that provide the Federal Emergency Management Agency (FEMA) and the rest of the federal response community assess and evaluate impacts of natural hazards on population and critical infrastructures including the status of the national electricity and oil and natural gas networks. These capabilities range from identifying structures or buildings from very high-resolution satellite imagery, utilizing machine learning and high-performance computing, to daily assessment of electricity restoration highlighting changes in nighttime lights for the impacted region based on the analysis of NOAA JPSS VIIRS Day/Night Band (DNB) imagery. This presentation will highlight our time critical mission support efforts for the 2017 hurricane season that witnessed unprecedented devastation from hurricanes Harvey, Irma, and Maria. ORNL provided 90m resolution LandScan USA population distribution data for identifying vulnerable population as well as structure (buildings) data extracted from 1m imagery for damage assessment. Spatially accurate data for solid waste facilities were developed and delivered to the response community. Human activity signatures were assessed from large scale collection of open source social media data around points of interests (POI) to ascertain level of destruction. The electricity transmission system was monitored in real time from data integration from hundreds of utilities and electricity outage information were provided back to the response community via standardized web-services.

Making vaccines “on demand”

PubMed Central

De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

2013-01-01

The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of “novel pathogens” such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process—from genome to gene sequence, ready to insert in a DNA plasmid—can now be accomplished in less than 24 h. While these vaccines are by no means “standard,” the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard. PMID:23877094

Public Health System Response to Extreme Weather Events.

PubMed

Hunter, Mark D; Hunter, Jennifer C; Yang, Jane E; Crawley, Adam W; Aragón, Tomás J

2016-01-01

Extreme weather events, unpredictable and often far-reaching, constitute a persistent challenge for public health preparedness. The goal of this research is to inform public health systems improvement through examination of extreme weather events, comparing across cases to identify recurring patterns in event and response characteristics. Structured telephone-based interviews were conducted with representatives from health departments to assess characteristics of recent extreme weather events and agencies' responses. Response activities were assessed using the Centers for Disease Control and Prevention Public Health Emergency Preparedness Capabilities framework. Challenges that are typical of this response environment are reported. Forty-five local health departments in 20 US states. Respondents described public health system responses to 45 events involving tornadoes, flooding, wildfires, winter weather, hurricanes, and other storms. Events of similar scale were infrequent for a majority (62%) of the communities involved; disruption to critical infrastructure was universal. Public Health Emergency Preparedness Capabilities considered most essential involved environmental health investigations, mass care and sheltering, surveillance and epidemiology, information sharing, and public information and warning. Unanticipated response activities or operational constraints were common. We characterize extreme weather events as a "quadruple threat" because (1) direct threats to population health are accompanied by damage to public health protective and community infrastructure, (2) event characteristics often impose novel and pervasive burdens on communities, (3) responses rely on critical infrastructures whose failure both creates new burdens and diminishes response capacity, and (4) their infrequency and scale further compromise response capacity. Given the challenges associated with extreme weather events, we suggest opportunities for organizational learning and preparedness improvements.

Engineering a responsive, low cost, tactical satellite, TACSAT-1

NASA Astrophysics Data System (ADS)

Hurley, M.; Duffey, T.; Huffine, Christopher; Weldy, Ken; Clevland, Jeff; Hauser, Joe

2004-11-01

The Secretary of Defense's Office of Force Transformation (OFT) is currently undertaking an initiative to develop a low-cost, responsive, operationally relevant space capability using small satellites. The Naval Research Laboratory (NRL) is tasked to be program manger for this initiative, which seeks to make space assets and capabilities available to operational users. TacSat-1 is the first in a series of small satellites that will result in rapid, tailored, and operationally relevant experimental space capabilities for tactical forces. Components of the resulting tactical architecture include a highly automated small satellite bus, modular payloads, common launch and payload interfaces, tasking and data dissemination using the SIPRNET (Secret Internet Protocol Routing Network), and low cost, rapid response launches. The overall goal of TacSat-1 is to demonstrate the utility of a broader complementary business model and provide a catalyst for energizing DoD and industry in the operational space area. This paper first provides a brief overview of the TacSat- 1 experiment and then discusses the engineering designs and practices used to achieve the aggressive cost and schedule goals. Non-standard approaches and engineering philosophies that allowed the TacSat-1 spacecraft to be finished in twelve months are detailed and compared with "normal" satellite programs where applicable. Specific subsystem design, integration and test techniques, which contributed to the successful completion of the TacSat-1 spacecraft, are reviewed. Finally, lessons learned are discussed.

Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

DTIC Science & Technology

2008-10-01

the fact that acute respiratory infections are one of the leading causes of morbidity. This capability now exists in Kenya with the first site brought...AD_________________ Award Number: W81XWH-07-2-0082 TITLE: Global Emerging Infection Surveillance and Response (GEIS)- Avian...TYPE Annual 3. DATES COVERED 13 Sep 07 – 12 Sep 08 4. TITLE AND SUBTITLE Global Emerging Infection Surveillance and Response (GEIS)- Avian

Responsive Plasma Polymerized Ultrathin Nanocomposite Films

DTIC Science & Technology

2012-01-01

29 74 32 75 Ab so rb an ce (a .u .) Wavenumber, cm-1 pNIPAAM A B C D E Fig . 2. FTIR spectra of A) NIPAAM monomer B) Spun- cast P-NIPAAM film and...self- actuating response to specific stimuli are desirable in a wide range of applications including thermalandchemical sensing, tunableoptics...targeteddrug delivery, switchable surfaces and micro actuators [1e6]. Designing materials which are capable of generating a response from the stim- ulus

Electroactive Polymer (EAP) Actuation of Mechanisms and Robotic Devices

NASA Technical Reports Server (NTRS)

Bar-Cohen, Y.; Leary, S.; Harrison, J.; Smith, J.

1999-01-01

Actuators are responsible to the operative capability of manipulation systems and robots. In recent years, electroactive polymers (EAP) have emerged as potential alternative to conventional actuators.

Are regional hospital pharmacies prepared for public health emergencies?

PubMed

Hsu, Edbert B; Casani, Julie A; Romanosky, Al; Millin, Michael G; Singleton, Christa M; Donohue, John; Feroli, E Robert; Rubin, Melvin; Subbarao, Italo; Whyne, Dianne M; Snodgrass, Thomas D; Kelen, Gabor D

2006-01-01

In the event of a major chemical, biological, radiological, nuclear, or explosive (CBRNE) attack or a natural disaster, large quantities of pharmaceuticals and medical supplies may be required with little or no warning. Pharmaceutical surge capacity for immediate response, before Strategic National Stockpile (SNS) supplies become available, remains a significant gap in emergency preparedness. To date, limited attempts have been made to assess collective regional hospital pharmaceutical response capabilities. In this project, we characterized the level of hospital pharmaceutical response preparedness in a major metropolitan region. The Johns Hopkins Office of Critical Event Preparedness and Response (CEPAR) convened a collaborative partnership to assess hospital pharmaceutical response capabilities. A survey was developed to characterize pharmaceutical response preparedness to CBRNE threats. All 22 acute care hospitals in the Maryland region were sent pharmaceutical response surveys, and responses were received from 86% (19/22). Within the past year, 84% (16/19) of hospitals had implemented an exercise with pharmacy participation. More than half of the hospitals expect to receive assistance from the SNS in 48 hours or less. Seventy-four percent (14/19) of the hospitals reported an additional dedicated reserve supply for biological events, 74% (14/19) for chemical events, and 58% (11/19) for radiological events. Many hospitals in this metropolitan region have taken important steps toward enhancing pharmaceutical preparedness. However, hospitals generally remain underprepared for CBRNE threats and collectively have limited supplies of antibiotics to provide prophylaxis or treatment for hospital staff, their families, and patients in the event of a significant biological incident.

Remote Sensing of Aquatic Plants.

DTIC Science & Technology

1979-10-01

remote sensing methods for identification and assessment of expanses of aquatic plants. Both materials and techniques are examined for cost effectiveness and capability to sense aquatic plants on both the local and regional scales. Computer simulation of photographic responses was employed; Landsat, high-altitude photography, side-looking airborne radar, and low-altitude photography were examined to determine the capabilities of each for identifying and assessing aquatic plants. Results of the study revealed Landsat to be the most cost effective for regional surveys,

Blast and Penetration Resistant Tactical Shelters

DTIC Science & Technology

1979-07-01

2. Hardened Wall Material Properties 32 3. S-280 Shelter Panal Properties 33 4. Results Zor Dynamic Response of Complete S-280 Shelters 32 £-". In...insulation from a -6501 low to a 120 0F high plus a solar heating load 7. Corrosion resistance including salt fog 8. Blackout capability 9. Fungus...65 0 F), high temperature (120 0 F) plus a solar heating (BTU) load. g. Corrosion resistance (salt fog). 19 h. Blackout capability. i. Fungus

Electroluminescent devices formed using semiconductor nanocrystals as an electron transport media and method of making such electroluminescent devices

DOEpatents

Alivisatos, A. Paul; Colvin, Vickie

1996-01-01

An electroluminescent device is described, as well as a method of making same, wherein the device is characterized by a semiconductor nanocrystal electron transport layer capable of emitting visible light in response to a voltage applied to the device. The wavelength of the light emitted by the device may be changed by changing either the size or the type of semiconductor nanocrystals used in forming the electron transport layer. In a preferred embodiment the device is further characterized by the capability of emitting visible light of varying wavelengths in response to changes in the voltage applied to the device. The device comprises a hole processing structure capable of injecting and transporting holes, and usually comprising a hole injecting layer and a hole transporting layer; an electron transport layer in contact with the hole processing structure and comprising one or more layers of semiconductor nanocrystals; and an electron injecting layer in contact with the electron transport layer for injecting electrons into the electron transport layer. The capability of emitting visible light of various wavelengths is principally based on the variations in voltage applied thereto, but the type of semiconductor nanocrystals used and the size of the semiconductor nanocrystals in the layers of semiconductor nanometer crystals may also play a role in color change, in combination with the change in voltage.

Multiple layer optical memory system using second-harmonic-generation readout

DOEpatents

Boyd, Gary T.; Shen, Yuen-Ron

1989-01-01

A novel optical read and write information storage system is described which comprises a radiation source such as a laser for writing and illumination, the radiation source being capable of radiating a preselected first frequency; a storage medium including at least one layer of material for receiving radiation from the radiation source and capable of being surface modified in response to said radiation source when operated in a writing mode and capable of generating a pattern of radiation of the second harmonic of the preselected frequency when illuminated by the radiation source at the preselected frequency corresponding to the surface modifications on the storage medium; and a detector to receive the pattern of second harmonic frequency generated.

IntelliTable: Inclusively-Designed Furniture with Robotic Capabilities.

PubMed

Prescott, Tony J; Conran, Sebastian; Mitchinson, Ben; Cudd, Peter

2017-01-01

IntelliTable is a new proof-of-principle assistive technology system with robotic capabilities in the form of an elegant universal cantilever table able to move around by itself, or under user control. We describe the design and current capabilities of the table and the human-centered design methodology used in its development and initial evaluation. The IntelliTable study has delivered robotic platform programmed by a smartphone that can navigate around a typical home or care environment, avoiding obstacles, and positioning itself at the user's command. It can also be configured to navigate itself to pre-ordained places positions within an environment using ceiling tracking, responsive optical guidance and object-based sonar navigation.

Station to instrumented aircraft L-band telemetry system and RF signal controller for spacecraft simulations and station calibration

NASA Technical Reports Server (NTRS)

Scaffidi, C. A.; Stocklin, F. J.; Feldman, M. B.

1971-01-01

An L-band telemetry system designed to provide the capability of near-real-time processing of calibration data is described. The system also provides the capability of performing computerized spacecraft simulations, with the aircraft as a data source, and evaluating the network response. The salient characteristics of a telemetry analysis and simulation program (TASP) are discussed, together with the results of TASP testing. The results of the L-band system testing have successfully demonstrated the capability of near-real-time processing of telemetry test data, the control of the ground-received signal to within + or - 0.5 db, and the computer generation of test signals.

Universal Documentation System Handbook. Volume 3. Response Formats and Instructions; Statement of Capability, Program Support Plan/Operations Directive

DTIC Science & Technology

1989-08-01

requesting agency and support agency which are not self -evident within the information content of the PI/SC or which involve deviations from policy; e.g...preparation instructions for Format 1000. RESPOSE ( ) INFOATION( ): Indicate whether each item number documented is a response for support or is

Response Time as an Indicator of Test Taker Speed: Assumptions Meet Reality

ERIC Educational Resources Information Center

Wise, Steven L.

2015-01-01

The growing presence of computer-based testing has brought with it the capability to routinely capture the time that test takers spend on individual test items. This, in turn, has led to an increased interest in potential applications of response time in measuring intellectual ability and achievement. Goldhammer (this issue) provides a very useful…

Dual enzyme responsive microcapsules simulating an "OR" logic gate for biologically triggered drug delivery applications.

PubMed

Radhakrishnan, Krishna; Tripathy, Jasaswini; Raichur, Ashok M

2013-06-14

Hollow microcapsules capable of disintegrating in response to dual biological stimuli have been synthesized from two FDA approved drug molecules. The capsules fabricated from protamine and chondroitin sulphate disintegrate in the presence of either trypsin or hyaluronidase enzymes, which are documented to be simultaneously over-expressed under some pathological conditions.

33 CFR 154.1228 - Methods of ensuring the availability of response resources by contract or other approved means.

Code of Federal Regulations, 2011 CFR

2011-07-01

... TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities... following methods: (1) The identification of an oil spill removal organization with specified equipment and... personnel, equipment, and services capable of being provided by the oil spill removal organization within...

33 CFR 154.1228 - Methods of ensuring the availability of response resources by contract or other approved means.

Code of Federal Regulations, 2010 CFR

2010-07-01

... TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities... following methods: (1) The identification of an oil spill removal organization with specified equipment and... personnel, equipment, and services capable of being provided by the oil spill removal organization within...

Responsibility beyond Rationality: The Case for Rhizomatic Consequentialism

ERIC Educational Resources Information Center

Stables, Andrew

2004-01-01

A key challenge for education is to encourage children to act responsibly. If "spiritual literacy" does not involve an autonomous, rational soul capable of "reading and writing the world as God intended", it must refer to ethical (and perhaps religious) capacity in relation to contingent actions in a context free of moral absolutes. In relation to…

44 CFR Appendix A to Part 353 - Memorandum of Understanding Between Federal Emergency Management Agency and Nuclear Regulatory...

Code of Federal Regulations, 2014 CFR

2014-10-01

... Commission on the Accident at Three Mile Island, directed that FEMA assume lead responsibility for all... can degrade the capabilities of offsite response organizations in the 10-mile plume emergency planning... affected offsite jurisdictions located in the 10-mile emergency planning zone and is not intended to be a...

44 CFR Appendix A to Part 353 - Memorandum of Understanding Between Federal Emergency Management Agency and Nuclear Regulatory...

Code of Federal Regulations, 2012 CFR

2012-10-01

... Commission on the Accident at Three Mile Island, directed that FEMA assume lead responsibility for all... can degrade the capabilities of offsite response organizations in the 10-mile plume emergency planning... affected offsite jurisdictions located in the 10-mile emergency planning zone and is not intended to be a...

Cholinergic Interneurons Mediate Fast VGluT3-Dependent Glutamatergic Transmission in the Striatum

PubMed Central

Higley, Michael J.; Balthasar, Nina; Seal, Rebecca P.; Edwards, Robert H.; Lowell, Bradford B.; Kreitzer, Anatol C.; Sabatini, Bernardo L.

2011-01-01

The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity. PMID:21544206

The effect of silicone-gel on the immune response.

PubMed

Naim, J O; Lanzafame, R J; van Oss, C J

1995-01-01

Silicone materials have been used in medical applications for at least 30 years. Despite this long history of use the question whether silicones can mediate an immunological reaction that may be detrimental to the host remains unanswered. Most studies on the biocompatability of silicones conclude that silicones are chemically stable compounds, which however are often capable of eliciting a benign chronic inflammatory response. Recently, our laboratory has conducted a series of animal experiments aimed at determining the immunological adjuvancy potential of silicone-gel taken from commercial breast implants. Our previous studies have indicated that silicone-gel is a potent humoral (antibody) adjuvant. Our present studies have found that silicone-gel is capable of eliciting auto-antibodies to rat thyroglobulin and bovine collagen II. However this immune response did not produce any histological evidence of thyroiditis or arthritis. Theories to explain why silicone-gel behaves as an adjuvant are discussed along with discussion of the hypothesis on the desirability of replacing silicone-gel with a more hydrophilic material in bioimplants.

A Mixed Multi-Field Finite Element Formulation for Thermopiezoelectric Composite Shells

NASA Technical Reports Server (NTRS)

Lee, Ho-Jun; Saravanos, Dimitris A.

1999-01-01

Analytical formulations are presented which account for the coupled mechanical, electrical, and thermal response of piezoelectric composite shell structures. A new mixed multi-field laminate theory is developed which combines "single layer" assumptions for the displacements along with layerwise fields for the electric potential and temperature. This laminate theory is formulated using curvilinear coordinates and is based on the principles of linear thermopiezoelectricity. The mechanics have the inherent capability to explicitly model both the active and sensory responses of piezoelectric composite shells in thermal environment. Finite element equations are derived and implemented for an eight-noded shell element. Numerical studies are conducted to investigate both the sensory and active responses of piezoelectric composite shell structures subjected to thermal loads. Results for a cantilevered plate with an attached piezoelectric layer are com- pared with corresponding results from a commercial finite element code and a previously developed program. Additional studies are conducted on a cylindrical shell with an attached piezoelectric layer to demonstrate capabilities to achieve thermal shape control on curved piezoelectric structures.

IRBs, conflict and liability: will we see IRBs in court? Or is it when?

PubMed

Icenogle, Daniel L

2003-01-01

The entire human research infrastructure is under intense and increasing financial pressure. These pressures may have been responsible for several errors in judgment by those responsible for managing human research and protecting human subjects. The result of these errors has been some terrible accidents, some of which have cost the lives of human research volunteers. This, in turn, is producing both increased liability risk for those who manage the various aspects of human research and increasing scrutiny as to the capability of the human research protection structure as currently constituted. It is the author's contention that the current structure is fully capable of offering sufficient protection for participants in human research-if Institutional Review Board (IRB) staff and members are given sufficient resources and perform their tasks with sufficient responsibility. The status quo alternative is that IRBs and their members will find themselves at great risk of becoming defendants in lawsuits seeking compensation for damages resulting from human experimentation gone awry.

Survey of computer programs for prediction of crash response and of its experimental validation

NASA Technical Reports Server (NTRS)

Kamat, M. P.

1976-01-01

The author seeks to critically assess the potentialities of the mathematical and hybrid simulators which predict post-impact response of transportation vehicles. A strict rigorous numerical analysis of a complex phenomenon like crash may leave a lot to be desired with regard to the fidelity of mathematical simulation. Hybrid simulations on the other hand which exploit experimentally observed features of deformations appear to hold a lot of promise. MARC, ANSYS, NONSAP, DYCAST, ACTION, WHAM II and KRASH are among some of the simulators examined for their capabilities with regard to prediction of post impact response of vehicles. A review of these simulators reveals that much more by way of an analysis capability may be desirable than what is currently available. NASA's crashworthiness testing program in conjunction with similar programs of various other agencies, besides generating a large data base, will be equally useful in the validation of new mathematical concepts of nonlinear analysis and in the successful extension of other techniques in crashworthiness.

Self-Powered, Flexible, and Solution-Processable Perovskite Photodetector Based on Low-Cost Carbon Cloth.

PubMed

Sun, Haoxuan; Lei, Tianyu; Tian, Wei; Cao, Fengren; Xiong, Jie; Li, Liang

2017-07-01

Flexible perovskite photodetectors are usually constructed on indium-tin-oxide-coated polymer substrates, which are expensive, fragile, and not resistant to high temperature. Herein, for the first time, a high-performance flexible perovskite photodetector is fabricated based on low-cost carbon cloth via a facile solution processable strategy. In this device, perovskite microcrystal and Spiro-OMeTAD (hole transporting material) blended film act as active materials for light detection, and carbon cloth serves as both a flexible substrate and a conductive electrode. The as-fabricated photodetector shows a broad spectrum response from ultraviolet to near-infrared light, high responsivity, fast response speed, long-term stability, and self-powered capability. Flexible devices show negligible degradation after several tens of bending cycles and at the extremely bending angle of 180°. This work promises a new technique to construct flexible, high-performance photodetectors with low cost and self-powered capability. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Langerhans Cells and Their Role in Oral Mucosal Diseases

PubMed Central

Upadhyay, Juhi; Upadhyay, Ram B; Agrawal, Pankaj; Jaitley, Shweta; Shekhar, Rhitu

2013-01-01

Dendritic cells are arguably the most potent antigen-presenting cells and may be the only cells capable of initiating the adaptive immune response. The epithelial residents of dendritic cells are Langerhans cells, which serve as the “sentinels” of the mucosa, altering the immune system not only to pathogen entry but also of tolerance to self antigen and commensal microbes. Oral mucosal Langerhans cells are capable of engaging and internalizing a wide variety of pathogens and have been found responsive to nickel in patients with nickel allergies, oral Candida species, oral lichen planus, lichenoid drug eruptions, graft versus host diseases, periodontal diseases median rhomboid glossitis, human immunodeficiency virus infection, hairy leukoplakia of the tongue, and oral squamous cell carcinoma. Review focuses on the role of antigen-presenting cells in particular Langerhans cells to better understand the mechanisms underlying immune responses. In this review, comprehensive detail about mucosal diseases has been compiled using the PubMed database and through textbooks. PMID:24251267

Fluorescent polymeric assemblies as stimuli-responsive vehicles for drug controlled release and cell/tissue imaging

NASA Astrophysics Data System (ADS)

Chang, Ying; Li, Yang; Yu, Shirong; Mao, Jie; Liu, Cheng; Li, Qi; Yuan, Conghui; He, Ning; Luo, Weiang; Dai, Lizong

2015-01-01

Polymer assemblies with good biocompatibility, stimuli-responsive properties and clinical imaging capability are desirable carriers for future biomedical applications. Herein, we report on the synthesis of a novel anthracenecarboxaldehyde-decorated poly(N-(4-aminophenyl) methacryl amide-oligoethyleneglycolmonomethylether methacrylate) (P(MAAPAC-MAAP-MAPEG)) copolymer, comprising fluorescent chromophore and acid-labile moiety. This copolymer can assemble into micelles in aqueous solution and shows a spherical shape with well-defined particle size and narrow particle size distribution. The pH-responsive property of the micelles has been evaluated by the change of particle size and the controlled release of guest molecules. The intrinsic fluorescence property endows the micelles with excellent cell/tissue imaging capability. Cell viability evaluation with human hepatocellular carcinoma BEL-7402 cells demonstrates that the micelles are nontoxic. The cellular uptake of the micelles indicates a time-dependent behavior. The H22-tumor bearing mice treated with the micelles clearly exhibits the tumor accumulation. These multi-functional nanocarriers may be of great interest in the application of drug delivery.

Multicomponent polymeric nanoparticles enhancing intracellular drug release in cancer cells.

PubMed

Ahmed, Arsalan; Liu, Sen; Pan, Yutong; Yuan, Shanmei; He, Jian; Hu, Yong

2014-12-10

Three kinds of amphiphilic copolymer, that is, poly(ε-caprolactone)-SS-poly(ethylene glycol) (PCL-SS-PEG), poly(ε-caprolactone)-polyethylenimine (PCL-PEI), and poly(ε-caprolactone)-polyethylenimine-folate (PCL-PEI-Fol) were synthesized and self-assembled into surface engineered hybrid nanoparticles (NPs). Morphological studies elucidated the stable, spherical, and uniform sandwich structure of the NPs. PCL-PEI and PCL-SS-PEG segments have introduced pH and reduction responsive characteristics in these NPs, while PCL-PEI-FA copolymers could provide specific targeting capability to cancer cells. The stimuli responsive capabilities of these NPs were carried out. Negative-to-positive charge reversible property, in response to the pH change, was investigated by zeta potential and nuclear magnetic resonance (NMR) measurements. The structure cleavage, due to redox gradient, was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM). These NPs showed controlled degradation, better drug release, less toxicity, and effective uptake in MCF-7 breast cancer cells. These multifunctional NPs showed promising potential in the treatment of cancer.

Organizational Context and Capabilities for Integrating Care: A Framework for Improvement

PubMed Central

Grudniewicz, Agnes; Baker, G. Ross; Wodchis, Walter P.

2016-01-01

Background: Interventions aimed at integrating care have become widespread in healthcare; however, there is significant variability in their success. Differences in organizational contexts and associated capabilities may be responsible for some of this variability. Purpose: This study develops and validates a conceptual framework of organizational capabilities for integrating care, identifies which of these capabilities may be most important, and explores the mechanisms by which they influence integrated care efforts. Methods: The Context and Capabilities for Integrating Care (CCIC) Framework was developed through a literature review, and revised and validated through interviews with leaders and care providers engaged in integrated care networks in Ontario, Canada. Interviews involved open-ended questions and graphic elicitation. Quantitative content analysis was used to summarize the data. Results: The CCIC Framework consists of eighteen organizational factors in three categories: Basic Structures, People and Values, and Key Processes. The three most important capabilities shaping the capacity of organizations to implement integrated care interventions include Leadership Approach, Clinician Engagement and Leadership, and Readiness for Change. The majority of hypothesized relationships among organizational capabilities involved Readiness for Change and Partnering, emphasizing the complexity, interrelatedness and importance of these two factors to integrated care efforts. Conclusions: Organizational leaders can use the framework to determine readiness to integrate care, develop targeted change management strategies, and select appropriate partners with overlapping or complementary profiles on key capabilities. Researchers may use the results to test and refine the proposed framework, with a focus on the hypothesized relationships among organizational capabilities and between organizational capabilities and performance outcomes. PMID:28413366

Broadband enhancement of dielectric light trapping nanostructure used in ultra-thin solar cells

NASA Astrophysics Data System (ADS)

Yang, Dong; Xu, Zhaopeng; Bian, Fei; Wang, Haiyan; Wang, Jiazhuang; Sun, Lu

2018-03-01

A dielectric fishnet nanostructure is designed to increase the light trapping capability of ultra-thin solar cells. The complex performance of ultra-thin cells such as the optical response and electrical response are fully quantified in simulation through a complete optoelectronic investigation. The results show that the optimized light trapping nanostructure can enhances the electromagnetic resonance in active layer then lead to extraordinary enhancement of both absorption and light-conversion capabilities in the solar cell. The short-circuit current density increases by 49.46% from 9.40 mA/cm2 to 14.05 mA/cm2 and light-conversion efficiency increases by 51.84% from 9.51% to 14.44% compared to the benchmark, a solar cell with an ITO-GaAs-Ag structure.

Cicada-inspired cell-instructive nanopatterned arrays

NASA Astrophysics Data System (ADS)

Diu, Ting; Faruqui, Nilofar; Sjöström, Terje; Lamarre, Baptiste; Jenkinson, Howard F.; Su, Bo; Ryadnov, Maxim G.

2014-11-01

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses. The rationale is inspired by cicada wing surfaces that display bactericidal nanopillar patterns. The surfaces engineered in this study are titania (TiO2) nanowire arrays that are selectively bactericidal against motile bacteria, while capable of guiding mammalian cell proliferation according to the type of the array. The concept holds promise for clinically relevant materials capable of differential physico-mechanical responses to cellular adhesion.

Cicada-inspired cell-instructive nanopatterned arrays.

PubMed

Diu, Ting; Faruqui, Nilofar; Sjöström, Terje; Lamarre, Baptiste; Jenkinson, Howard F; Su, Bo; Ryadnov, Maxim G

2014-11-20

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses. The rationale is inspired by cicada wing surfaces that display bactericidal nanopillar patterns. The surfaces engineered in this study are titania (TiO2) nanowire arrays that are selectively bactericidal against motile bacteria, while capable of guiding mammalian cell proliferation according to the type of the array. The concept holds promise for clinically relevant materials capable of differential physico-mechanical responses to cellular adhesion.

King has no clothes: The role of the military in responding to a terrorist chemical/biological attack. Final report

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

Osterman, J.L.

1996-06-14

The United States has begun a program of counterproliferation in order to preempt the use of WMD by such elements, however, the ability to respond to the terrorist employment of biological/chemical weapons is absent. Given the structure, capability and technical expertise in the Federal Emergency Management Agency (FEMA) and the Federal Bureau of Investigation (FBI), the Department of Defense (DoD) will be tasked to conduct the response to such an incident. The geographical Commander in Chief (CINC) and the appointed Joint Task Force (JTF) commander will ultimately be assigned the response mission. Planning, training and coordination is required to developmore » a force capable of responding in a timely and coordinated manner.« less

Researching pharmacist managerial capability: philosophical perspectives and paradigms of inquiry.

PubMed

Woods, Phillip; Gapp, Rod; King, Michelle A

2015-01-01

In successful community pharmacy business enterprises suitably responsive actions to meet ever-increasing change require capable pharmacy managers who readily learn and adapt. Capability as a concept is generally understood to be the ability of a manager to identify and act to solve unfamiliar problems in unfamiliar situations. Capability is characterized by adaptability and flexibility. However, different understandings of the concept 'capability' and what it means to be 'capable' are indirect and incomplete. This paper aims to clarify current theories regarding the concept of 'capability' at the level of the individual, and through this to make more explicit what is known about the phenomenon, but more particularly, how we know what we know. The analysis includes the concept of 'competence' because explanations of capability include competence, and the two concepts are not clearly separated in the literature. By probing the epistemological origins of current theory concerning both concepts, the limiting taken for granted assumptions are revealed. Assumptions about context and time, and the psychological theory through which individuals are assumed to perceive, know and learn, are illuminated. The analysis, in connection with the literature, shows how the interpretive philosophic research approach may reveal a different and useful theoretical perspective for explaining capability as a dynamic performance. It is suggested that such a perspective may narrow the gap between the theory of capability and its practice. The interpretive perspective holds potential to reveal how capability, as performed by successful community pharmacy managers, might be further researched and strengthened. This paper supports the challenging suggestion that pharmacy social research needs to rebalance the dominance of purely empirical research by exploring interpretive methodologies to better understand human actions and relations in the context of pharmacy. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.